cssi/SciSciGPT-SciSciNet huggingface dataset:
A retrospective analysis of treatment-related hospitalization costs of pediatric, adolescent, and young adult acute lymphoblastic leukemia

This retrospective study examined the longitudinal hospital outcomes (costs adjusted for inflation, hospital days, and admissions) associated with the treatment of pediatric, adolescent, and young adult acute lymphoblastic leukemia (ALL). Patients between one and 26 years of age with newly diagnosed ALL, who were treated at Primary Children's Hospital (PCH) in Salt Lake City, Utah were included. Treatment and hospitalization data were retrieved from system-wide cancer registry and enterprise data warehouse. PCH is a member of the Children's Oncology Group (COG) and patients were treated on, or according to, active COG protocols. Treatment-related hospital costs of ALL were examined by computing the average annual growth rates (AAGR). Longitudinal regressions identified patient characteristics associated with costs. A total of 505 patients (46.9% female) were included. The majority of patients had B-cell lineage ALL, 6.7% had T-ALL, and the median age at diagnosis was 4 years. Per-patient, first-year ALL hospitalization costs at PCH rose from $24,197 in 1998 to $37,924 in 2012. The AAGRs were 6.1, 13.0, and 7.6% for total, pharmacy, and room and care costs, respectively. Average days (AAGR = 5.2%) and admissions (AAGR = 3.8%) also demonstrated an increasing trend. High-risk patients had 47% higher costs per 6-month period in the first 5 years from diagnosis than standard-risk patients (P < 0.001). Similarly, relapsed ALL and stem cell transplantations were associated with significantly higher costs than nonrelapsed and no transplantations, respectively (P < 0.001). Increasing treatment-related costs of ALL demonstrate an area for further investigation. Value-based interventions such as identifying low-risk fever and neutropenia patients and managing them in outpatient settings should be evaluated for reducing the hospital burden of ALL.
Comment on: Structure, transport, and vertical coherence of the Gulf Stream from the Straits of Florida to the Southeast Newfoundland Ridge, by Meinen and Luther

Abstract Remarkably low vertical coherences in downstream velocities have been reported recently for three alongstream locations in the Gulf Stream, a Western Boundary Current with known three-dimensional dynamics of a baroclinically and barotropically unstable jet. This comment addresses the possibility that spatial averaging of coherences may be contributing to the low values estimated.
Measurement of p-Toluenesulfonic Acid-Catalyzed Reaction Kinetics of 1,2-Propylene Glycol Acetylation Using In Situ1H NMR Spectroscopy

The reaction kinetics for the acetylation of 1,2-propylene glycol (PG) catalyzed by p-toluenesulfonic acid (p-TSA) were determined using an in situ1H NMR method. Both primary and secondary monoacetate esters of PG were observed as well as the diester. The reaction kinetics were characterized as a function of PG to acetic acid (AA) stoichiometry, p-TSA concentration, and temperature. The acetylation reactions and the transacetylation of the diester with PG were modeled as reversible second order reactions. Equilibrium constants were determined experimentally for each reaction. Activation energies for the consecutive acetylation of PG and PG monoacetate ester (PGMA) were 56 and 47 kJ/mol, respectively. The activation energy for intermolecular transacetylation of PG with its diacetate ester to form PG monoacetate was 63 kJ/mol.
Miscarriages of Justice and the Constitution

Accurate fact-finding surely counts as a primary purpose of criminal procedure. Conventional wisdom holds that our system is highly successful at preventing erroneous convictions, but far less successful at preventing erroneous acquittals or dismissals. This asymmetry is commonly attributed to the rights of the accused, particularly the constitutional safeguards in the Bill of Rights. This essay challenges the conventional wisdom on three important fronts. First, while the common belief that many guilty people go unwhipped of justice accords with the facts, the prevailing belief that few innocent people are convicted seems quite improbable. Our criminal justice system, then, needs to do better at both convicting the guilty and acquitting the innocent. Second, despite the Warren Court’s criminal procedure revolution, constitutional law does remarkably little to prevent unjust convictions. The criminal procedure revolution made the Bill of Rights for the most part applicable to the states through the Fourteenth Amendment. The Bill of Rights, however, provides quite inadequate safeguards against unjust conviction. The Fifth
Comparing van der Waals Density Functionals for CO2 Adsorption in Metal Organic Frameworks

The accuracy of five recently proposed van der Waals (vdW) density functionals (optB86b, optB88, optPBE, revPBE, and rPW86), the semiempirical vdW method of Grimme (DFT-D2), and conventional local (LDA) and gradient-corrected (GGA-PBE) density functionals are assessed with respect to experimental enthalpies (ΔH) for CO2 adsorption in four prototypical metal organic frameworks (MOFs) containing coordinatively unsaturated metal sites: M/DOBDC (M = Mg, Ni, and Co) and Cu-HKUST-1. Although the LDA and GGA functionals partially capture trends, they significantly overbind (LDA) and underbind (GGA) CO2 with respect to the experimental enthalpies. The addition of a semiempirical r–6 dispersion term to the GGA exchange-correlation energy using “off the shelf” DFT-D2 parameters results in a substantial improvement both in trends and in the magnitude of the adsorption enthalpies. However, on average this approach still underbinds CO2 as compared to the experimental data by ∼7 kJ/mol (18%). Better accuracy is obtaine...
Intracellular Inhibitory Effects of Velcade Correlate with Morphoproteomic Expression of Phosphorylated-Nuclear Factor-κB and p53 in Breast Cancer Cell Lines

Velcade, a proteasome inhibitor, has been shown to inhibit DNA binding activity of nuclear factor-kappaB (NF-kappaB) and to stabilize p53 in vitro. But its impact, in the context of activated (phosphorylated and translocated) NF-kappaB and the expression of p53, has not been studied in breast cancer. It would be desirable to determine whether or not the immunohistochemical (IHC) expressions of activated NF-kappaB and of p53 can predict the effects of Velcade in viable tumor cells. To answer these questions, we selected 3 breast cancer cell lines (SKBR-3, MDA-175, and MDA-231), which are negative for hormonal receptors, but differ in HER-2/neu expression (strong, mild, and minimal, respectively). The 3 cell lines showed different expressions of phosphorylated (p)- NF-kappaB and p53, as evaluated using immunohistochemistry with visual quantification by brightfield microscopy. After being treated with Velcade for 2 days, MDA-231 cells showed markedly reduced proliferation, followed by SKBR-3 cells, and then by MDA-175 cells. There was strong correlation between the nuclear expression of either p-NF-kappaB or p53 and the inhibitory rate of Velcade in the 3 cell lines (r = 0.987 and 0.807, respectively). Western blotting showed an increase in inhibitor-kappaB (I-kappaB) expression in nuclei of MDA-231 and SKBR-3 cells, but not in MDA-175 cells, following exposure to Velcade. Velcade treatment resulted in cleaved caspase-3 expression in MDA-231 cells and in the overexpression of p53 and p21WAF1 in all 3 cell lines, as evaluated using Western blotting. In summary, morphoproteomic analysis of p-NF-kappaB and p53 can be correlated with the inhibitory effect of Velcade in vitro. We propose that this proliferative inhibition is variably associated with blocking p-NF-kappaB function by upregulation of nuclear I-kappaB, stabilization of p53, and induction of p21WAF1.
Perspectives on the Distributions of ESD Breakdowns for Spacecraft Charging Applications

Electrostatic discharge (ESD) continues to pose significant risks to space missions despite decades of intense study. Tabulated values of material breakdown strength used in spacecraft charging models are often based on cursory measurements that may not be fully relevant to a given mission. Materials physics offers insight into the pertinent variables that affect breakdown and how to address them experimentally for spacecraft applications. We present measured distributions of ESD data across several test configurations for three polymeric materials that, taken together, begin to provide an understanding of how to estimate the likelihood of ESD events over a spacecraft’s mission lifetime. We discuss how consequences of these results apply to spacecraft charging modeling and design considerations.
Clinical and economic outcomes of an ambulatory urinary tract infection disease management program.

OBJECTIVE: To evaluate the effectiveness of a urinary tract infection disease management program. STUDY DESIGN: A pre-post design was used. One year of data before and after promoting the treatment guideline were compared. PARTICIPANTS AND METHODS: A 300,000-member managed care organization introduced an antibiotic treatment guideline designed to change the antibiotic prescribing practices of community physicians. The study intervention was the promotion of a treatment guideline through mailings and face-to-face interventions by 2 disease management specialists. A relational database was created to measure changes in healthcare resources, use of antibiotics, and health event profiles. RESULTS: The study demonstrated that prescribing patterns could be modified through treatment guideline distribution and face-to-face discussions. The study also found similar success rates across a range of antibiotics. Average health event costs decreased by 36% for kidney infections (P = .696) and by 7% for bladder infections (P < .05) after the treatment guideline was implemented; however, when controlling for patient age, sex, and comorbidities, the econometric model did not find a reduction in health event costs for either kidney or bladder infections. Fluoroquinolones were a cost driver compared with other antibiotics used to treat kidney and bladder infections. CONCLUSIONS: Consideration should be given to expanding the number of well-established antibiotics on the treatment guideline. Also, fluoroquinolones should be reserved for patients with sulfa allergies or failures with initial antibiotic treatment. In addition, it is recommended that future costs and outcomes be assessed after changes are made to the treatment guideline.
Physiologic Mechanisms by Which Local Anesthetics May Cause Injury to Nerve and Spinal Cord

Objective. Review evidence for possible physiologic mechanisms by which local anesthetics cause nerve injury was reviewed. Methods. Published clinical case reports, and both in vivo and in vitro experimental studies in animals, were reviewed. Reports with direct bearing on possible mechanisms of local anesthetic neurotoxicity were included. Results. There is basic and clinical evidence that local anesthetics can cause nerve injury. Nerve injury may result from direct toxicity to the axon or Schwann cell, or may be secondary to disruption of the nerve microenvironment. Although each of these possibilities is supported by published experiments, injury to the axon is the most likely explanation for persistent neurologic deficits, such as those believed to result from clinical use of local anesthetics. Whether the injury is direct or indirect, and the precise mechanism by which it occurs, has received only limited study. Conclusions. In rare instances, the clinical use of local anesthetics is associated with neurologic morbidity. The physiologic mechanisms of toxicity for which there is the best evidence are inhibition of fast axonal transport, disruption of the axonal cytoskeleton, axonal degeneration, and ischemic nerve injury. The effects of local anesthetics on nerve blood flow may be related to inhibition of endothelium-dependent vasodilation or interruption of the synthesis of vasodilating prostaglandins. Both the prevention and the treatment of nerve injury caused by local anesthetics requires information that is not yet available about the physiologic and molecular mechanisms for direct neural toxicity of local anesthetics.
Progress towards the Synthesis of Amino Polyesters via Ring-Opening Polymerization (ROP) of Functional Lactones

Amine-functionalized polyesters are an important class of materials for biomedical applications due to their utility in gene and drug delivery, bioconjugation reactions, hydrogels, and controlled release systems. The synthesis of amino polyesters by ring-opening polymerization (ROP) is an ongoing challenge that is being aided by advances in reaction development. For the benefit of this important research area, this article highlights the related works of synthesizing amino polyesters by ROP as well as our recent synthesis of a new library of amino polyesters from amine-functionalized lactone monomers. 1 Polymerization of Lactone Monomers with Unprotected Amine Functionalities 2 Synthesis of Amino-Functionalized Polyesters via Postpolymerization Modification of Functionalized Monomers 3 Design of Novel Amino-Functionalized Lactone Monomers and Direct Synthesis of Amino Polyesters
Dynamics of ferrofluid drop deformations under spatially uniform magnetic fields

We systematically study the shape and dynamics of a Newtonian ferrofluid drop immersed in an immiscible, Newtonian and non-magnetic viscous fluid under the action of a uniform external magnetic field. We obtain the exact equilibrium drop shapes for arbitrary ferrofluids, characterize the extent of deviations of the exact shape from the commonly assumed ellipsoidal shape, and analyse the smoothness of highly curved tips in elongated drops. We also present a comprehensive study of drop deformation for a Langevin ferrofluid. Using a computational scheme that allows fast and accurate simulations of ferrofluid drop dynamics, we show that the dynamics of drop deformation by an applied magnetic field is described up to a numerical factor by the same time scale as drop relaxation in the absence of any magnetic field. The numerical factor depends on the ratio of viscosities and the ratio of magnetic to capillary stresses, but is independent of the nature of the ferrofluid in most practical cases.
Active Snort Rules and the Needs for Computing Resources: Computing Resources Needed to Activate Different Numbers of Snort Rules

This project was designed to discover the relationship between the number of enabled rules maintained by Snort and the amount of computing resources necessary to operate this intrusion detection system (IDS) as a sensor. A physical environment was set up to loosely simulate a network and an IDS sensor monitoring it. The experiment was conducted in five trials. A different number of Snort rules was enabled in each trial and the corresponding utilization of computing resources was measured. Remarkable variation and a clear trend of CPU usage were observed in the experiment.
Anesthesia for Outpatient Dental Procedures

While a significant amount of dental procedures can be done in a dentist’s office with local anesthetic, there are circumstances when the patient’s medical comorbidities require additional monitoring and deeper levels of sedation than can be provided in an outpatient office. These may range in spectrum from mild anxiolysis performed by a dentist, to general anesthesia performed by an anesthesiologist. The content below offers an overview of human dental anatomy, dental notation, levels of sedation, common anxiolytics and anesthetic practices, adverse events, and guidelines for the management of dental anesthesia.
Measuring manhood: race and the science of masculinity, 1830–1934

In this fascinating expose of American scientific history, Melissa Stein explores the impact constructions of gender (particularly, notions of manhood) had on race-making. In the postbellum era, Am...
Support for caregivers delayed time to nursing home placement in Alzheimer disease

Source Citation Mittelman MS, Ferris SH, Shulman E, Steinberg G, Levin B. A family intervention to delay nursing home placement of patients with Alzheimer disease. A randomized controlled trial. JA...
Bosonic tensor models at large $N$ and small $\epsilon$

We study the spectrum of the large $N$ quantum field theory of bosonic rank-3 tensors, the quartic interactions of which are such that the perturbative expansion is dominated by the melonic diagrams. We use the Schwinger-Dyson equations to determine the scaling dimensions of the bilinear operators of arbitrary spin. Using the fact that the theory is renormalizable in $d=4$, we compare some of these results with the $4\ensuremath{-}\ensuremath{\epsilon}$ expansion, finding perfect agreement. This helps elucidate why the dimension of operator ${\ensuremath{\phi}}^{abc}{\ensuremath{\phi}}^{abc}$ is complex for $dl4$: the large $N$ fixed point in $d=4\ensuremath{-}\ensuremath{\epsilon}$ has complex values of the couplings for some of the $O(N{)}^{3}$ invariant operators. We show that a similar phenomenon holds in the $O(N{)}^{2}$ symmetric theory of a matrix field ${\ensuremath{\phi}}^{ab}$, where the double-trace operator has a complex coupling in $4\ensuremath{-}\ensuremath{\epsilon}$ dimensions. We also study the spectra of bosonic theories of rank-$q\ensuremath{-}1$ tensors with ${\ensuremath{\phi}}^{q}$ interactions. In dimensions $dg1.93$, there is a critical value of $q$, above which we have not found any complex scaling dimensions. The critical value is a decreasing function of $d$, and it becomes 6 in $d\ensuremath{\approx}2.97$. This raises a possibility that the large $N$ theory of rank-5 tensors with sextic potential has an IR fixed point which is free of perturbative instabilities for $2.97ldl3$. This theory may be studied using renormalized perturbation theory in $d=3\ensuremath{-}\ensuremath{\epsilon}$.
Elephant in the Room: Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors.

See Article by Doshi et al In this issue of Circulation: Cardiovascular Quality and Outcomes , Doshi et al1 raise the issue of whether the prior authorization (PA) program requirements are particularly excessive for the proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) drug class. The authors report on the burden of the PA process for PCSK9i using a unique proprietary database that includes detailed information on PA requirements for 3872 public and private insurance plans. They found that there were greater PA requirements for PCSK9i than for other brand name cardiometabolic drugs used as comparators (ezetimibe, liraglutide). Although it is often expected that government bureaucracy exceeds that in the private sector, this study found that in contrast, it was the non-Medicare plans that had 3× to 11× more fields required for PA form completion than comparator drugs. In particular, health insurance exchange plans established by the Affordable Care Act had the highest burden of criteria to fulfill the PA submission process. A high-burden PA process may be related to high rates of rejection for submitted PCSK9i prescriptions because other studies have reported that commercial payers also had the lowest PA approval rates.2,3 Why are we examining the intricate details of the PCSK9i PA process and high rejection rates? The reason is clear—simply put, these drugs are expensive and at a level not previously seen for a drug with this potentially large of a market. This is the elephant in the room. Cost-effectiveness analyses of PCSK9i have not been favorable. Multiple studies using a variety of sensitivity analyses and approaches all suggest that annual PCSK9i costs must be reduced by 60% to 70%, down to $4000 to $5000 …
Treating Bipolar Disorders

Bipolar disorder was previously considered only present in adults, but more recently there has been a rise in diagnoses of bipolar disorder in children. Risk factors may include parental factors or comorbid cognitive and behavioral disorders or symptoms. Psychological interventions (e.g., psychoeducational, cognitive behavioral, dialectic behavioral) and psychopharmacological treatments are commonly used to treat children diagnosed with bipolar disorder. Much of the research literature has focused on medication use, which can have significant negative side effects, and additional research on psychological interventions is warranted.
Optimum Threshold Level of Degrading Systems Based on Sensor Observation

Degradation models are normally used to predict the system’s failure under condition-based predictive maintenance policies. Repairs or replacements of the system are performed once the degradation level reaches a predetermined threshold level. This results in a significant time and cost savings compared to the situation when the system is repaired upon failure. In the former case, the maintenance is planned and the necessary spare parts and manpower requirements are readily available, while in the latter case it is difficult to predict the failure time and plan the necessary resources to perform the maintenance action immediately upon failure. Recent developments in sensors, chemical and physical nondestructive testing, and sophisticated measurement techniques have facilitated the continuous monitoring of the system condition. A condition parameter could be any critical characteristic such as crack growth, vibration, corrosion, wear and lubricant condition. With the measured data, the predictive maintenance policy determines the optimum threshold level at which maintenance action is performed to bring the system to a “better” condition, if not as good as new, in order to maximize system availability or minimize the average maintenance cost.
Conservative Dynamical Systems and Nonlinear Livsic-Brodskii Nodes

We review some ideas on conservative dynamical systems and show how this leads to the notion of a nonlinear Livsic-Brodskii node, where the vector field A(x) defining the internal dynamics for the system replaces the linear operator A appearing in the linear theory. We show that under certain hypotheses two vector fields leading to the same Livsic-Brodskii characteristic input-outmap map are equivalent via an energy-preserving diffeomorphic change of variable, a nonlinear analogue of one of the main theorems in the linear theory. We also survey related issues concerning lossless and dissipative systems for both the linear and nonlinear case, including an application to the standard problem of H ∞-control theory.
Proceedings of the 5th ACM SIGPLAN workshop on Declarative aspects of multicore programming

Welcome to the fifth Workshop on Declarative Aspects of Multicore Programming -- DAMP 2010. The advent of multicore architectures has profoundly increased the importance of research in parallel computing. Modern platforms are becoming more complex and heterogenous and novel solutions are needed to account for their peculiarities. Multicore architectures differ in significant ways from their multisocket predecessors. For example, the communication to compute bandwidth ratio is likely to be higher, which positively impacts performance. More generally, multicore architectures introduce several new dimensions of variability in both performance guarantees and architectural contracts, such as the memory model, that may not stabilize for several generations of product. Programs written in functional or (constraint-) logic programming languages, or in other highly declarative languages with a controlled use of side effects, can greatly simplify parallel programming. Such declarative programming allows for a deterministic semantics even when the underlying implementation might be highly non-deterministic. In addition to simplifying programming this can simplify debugging and analyzing correctness. DAMP 2010 is the fifth in a series of one-day workshops seeking to explore ideas in declarative programming language design that will greatly simplify programming for multicore architectures, and more generally for tightly coupled parallel architectures. The emphasis is on (constraint) logic and functional programming, but any declarative programming language ideas that aim to raise the level of abstraction are welcome. DAMP seeks to gather together researchers in declarative approaches to parallel programming and to foster cross fertilization across different approaches. The call for papers generated 12 submissions, from Germany, UK, Italy, the Netherlands, and the US. Maintaining its traditional high-quality standards, the Program Committee selected 8 papers for inclusion in the final workshop program. In addition to the refereed papers, the final program includes two invited presentations, by Laurent Michel (University of Connecticut) and Satnam Singh (Microsoft Research).
Heterocyclic Aromatic Amines: Potential Human Carcinogens

Heterocyclic aromatic amines (HAAs) are formed at parts per billion concentrations during the cooking of meats, poultry, and fish. All of the HAAs tested thus far are carcinogenic in experimental animals and induce tumors in multiple organs. Because of the presence of HAAs in a wide range of food items, the exposure to them can be appreciable. Some epidemiological studies have linked an increased risk for cancer development of the colon, prostate, and female mammary gland with frequent consumption of well-done cooked meats containing HAAs. Therefore, much research has been devoted to determining the potential role of HAAs in the etiology of human cancer. This chapter highlights investigations on the biochemistry of metabolism of several prototypical HAAs, the formation of DNA adducts by these HAAs and the ensuing biological effects, and the analytical approaches that are employed for biomonitoring of these procarcinogens in humans.
Molecular Pathology of Alzheimer’s Disease and Related Disorders

Alzheimer’s disease (AD) is characterized clinically by memory deficits and progressive cognitive decline leading to incapacitating dementia and death. Gross examination of the AD brain indicates that the cerebral cortex is most severely affected, with notable atrophy of the medial temporal lobe, temporal pole (including the subcortical amygdala), midfrontal, and orbitofrontal cortex. Pathologically, the disease is characterized by the deposition of filamentous material in intracellular and extracellular compartments in the form of neurofibrillary tangles (NFTs), neuropil threads (NTs), and senile plaques (SPs), predominantly within the hippocampal formation (entorhinal cortex, Amnion’s horn—CA1, CA2, CA3, and CA4—dentate gyrus, and subicular complex) and neocortex (the secondary association and polymodal cortex). Additionally, subsets of neurons appear selectively vulnerable to neurodegeneration within the AD brain, including GA1 pyramidal neurons of the hippocampal formation and layers II, III, and V corticocortical projection neurons of secondary association cortex, leading to regionally specific synaptic and connectivity-based degeneration (see Hof et al., this volume). A diagnosis of AD is made postmortem on aged patients who display progressive cognitive decline and the presence of abundant NFTs and SPs with dystrophic processes—the so-called neuritic plaque—upon microscopic evaluation of hippocampus and neocortex.
Detection of broadleaf weeds growing in turfgrass with convolutional neural networks

BACKGROUND Weed infestations reduce turfgrass aesthetics and uniformity. Postemergence (POST) herbicides are applied uniformly on turfgrass, hence areas without weeds are also sprayed. Deep learning, particularly the architecture of convolutional neural network (CNN), is a state-of-art approach to recognition of images and objects. In this paper, we report deep learning CNN (DL-CNN) models that are remarkably accurate at detection of broadleaf weeds in turfgrasses. RESULTS VGGNet was the best model for detection of various broadleaf weeds growing in dormant bermudagrass [Cynodon dactylon (L.)] and DetectNet was the best model for detection of cutleaf evening-primrose (Oenothera laciniata Hill) in bahiagrass (Paspalum notatum Flugge) when the learning rate policy was exponential decay. These models achieved high F1 scores (>0.99) and overall accuracy (>0.99), with recall values of 1.00 in the testing datasets. CONCLUSION The results of the present research demonstrate the potential for detection of broadleaf weed using DL-CNN models for detection of broadleaf weeds in turfgrass systems. Further research is required to evaluate weed control in field conditions using these models for in situ video input in conjunction with a smart sprayer. © 2019 Society of Chemical Industry.
GENETIC EFFECTS ON MU-OPIOID RECEPTOR LIGAND BIASED SIGNALING

Background The mu-opioid receptor, a G Protein-Coupled Receptor (GPCR), has been shown to be associated with alcohol and substance use disorders. Specific genetic mutations have been shown, in our studies and those of others, to affect propensity towards addiction and pharmaceutical response; however, the mechanism responsible remains largely unknown. A better understanding could assist the development of personalized therapeutics. Recently, the role of ligand-biased downstream cellular signaling in mu receptors has become an active area of interest, but the role of genetic variation in this context has not been considered. In this study, we explore whether ligand-induced downstream signaling pathways are biased across mu-opioid receptor polymorphisms. Methods We are testing two Single Nucleotide Polymorphisms (SNPs) that change protein sequence, C17T and A118G, which exist on the N-terminal domain of the mu receptor and are common in human populations. Additionally, we are testing a rhesus macaque SNP, C77G, which appears to be functionally and behaviorally parallel. Here, we first transduce transcriptional response element inducible luciferase reporters from four pathways (NFkB, cAMP, MAPK/ERK, and MAPK/JNK) into multiple cell lines (SK-N-MC, CHO and HEK 293). We then transfect in a plasmid containing the specific variation of the mu opioid receptor and generate a concentration response curve with DAMGO, beta-endorphin, or morphine. Results Our previous work has demonstrated the effects of both human and rhesus polymorphisms on cAMP signaling pathways for morphine, DAMGO and beta-endorphin. For the NFkB signaling pathway, in both humans and rhesus macaques, significant differences in potency of morphine, beta-endorphin have been observed, but not DAMGO. Both human C17:G118 and T17:A118 have higher potencies for these ligands. A similar pattern is seen in the derived G77 allele in rhesus macaques. Discussion Preliminary data suggests that a mechanism by which polymorphisms in the mu opioid receptor exert their effects is through differential downstream signaling in addition to differential potencies. This has implications not only for understandings of the means by which the mu opioid receptor affects behaviors, but also for how genetic differences are likely to affect novel biased ligands.
Keep Your Friends Close: Exploring the Associations of Bullying, Peer Social Support, and Social Anxiety

The current study investigated the relationship between victimization experiences (including traditional and cyber-victimization) and social support from two different groups of peers (classmates and close friends) in relation to social anxiety during adolescence. Specifically, this study investigated the social deterioration hypothesis to understand whether the experience of victimization, both in person and online, would influence student perceptions of support from their general classmates and close friends and, whether through this relationship, influence student reports of social anxiety. Six hundred and sixty nine students completed the Child and Adolescent Social Support Scale (CASSS; Malecki, Demaray, & Elliott 2000), the Cyberbullying and Victimization Survey (CVS; Brown, Demaray, & Secord 2014), the Bullying Participant Behavior Questionnaire (BPBQ; Demaray, Summers, Jenkins, & Becker 2014), and the Social Anxiety Scale for Adolescents (SAS; La Greca and Lopez 1998). Results found support for the social deterioration hypothesis. In other words, student reports of victimization experiences were associated with reports of support from classmates. However, important gender differences in these relationships emerged, and greater support for this hypothesis was found for girls than for boys. Implications of the current study are discussed within the context of school-based mental health support services.
Unifying Real-Time Telemetry for Fun and Profit in Packet-Optical Networks

Emerging packet-optical networks have imposed new flexibility requirements of network telemetry. We introduce a framework based on programmable data planes to address these requirements and unify telemetry across packet and optical network segments.
konfound: Command to quantify robustness of causal inferences:

Statistical methods that quantify the discourse about causal inferences in terms of possible sources of biases are becoming increasingly important to many social-science fields such as public polic...
Synergism between microRNA-124 and ELAVL3 drives neuronal gene upregulation during direct neuronal reprogramming of human fibroblasts

Summary Human neurons generated by direct conversion of adult fibroblasts can serve instrumental tools for modeling diseases as well as a platform to study neurogenic processes. Neuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed. A critical component of the miRNA-mediated conversion process is the role of miR-9/9*-124 targeting and repressing anti-neurogenic genes. However, how these miRNAs function beyond the onset of the neuronal program remains unclear. Here, we performed the Argonaute (AGO) HITS-CLIP analysis to map direct target transcripts of miR-9/9*-124 when cells start adopting the neuronal fate during the conversion (reprogramming) process. Surprisingly, we found that miR-124, in particular, targets a suite of genes associated with neuronal differentiation and function, and these targets appeared to be upregulated by miR-124, as knocking down miR-124 function diminished the expression of these targets. A critical example of the upregulated miR-124 target genes is PTBP2, a neuron-enriched RNA-binding protein known to be repressed by its homolog PTBP1. We elected to focus on PTBP2 to gain insights into the mechanism underlying the activity of miR-124 as an inducer of its target genes. Paradoxically, both PTBP1 and PTBP2 are repressive targets of miR-124 in non-neuronal cells, yet PTBP2 selectively escapes the repression and becomes enriched in neurons. By interrogating 3’UTR sequences of PTBP1 and PTBP2, we provide evidence that the switching of miR-124 activity to an activator is determined by the sequence availability at the target transcript that allows the binding of neuronal RNA-binding proteins, in particular ELAVL3 for select upregulation of PTBP2. ELAVL3 binds and interacts with AGO at PTBP2 3’UTR, yet ELAVL3 binding alone without miR-124 sites is insufficient to trigger the upregulation of PTBP2. Knocking down ELAVL3 expression during neuronal reprogramming leads to PTBP2 downregulation and impairs neuronal conversion, highlighting the concerted interplay between miR-124 and ELAVL3 that drives neuronal fate acquisition. By elucidating how miR-124 promotes PTBP2 induction, our study lends support to the underexplored role of miRNAs in promoting target gene expression in neurons.
The people of the river: nature and identity in black Amazonia, 1835-1945

The history of black political activism in the Americas is not, as scholars of the African Diaspora often remind us, a recent development. The Atlantic slave trade and plantation slavery threatened...
Protecting the Guild or Protecting the Public? Bar Exams and the Diploma Privilege

The bar examination has long loomed over legal education. Although many states formerly admitted law school graduates into legal practice via the diploma privilege, Wisconsin is the only state that recognizes the privilege today. The bar examination is so central to the attorney admissions process that all but a handful of jurisdictions required it amidst a pandemic that turned bar exam administration into a life-or-death matter. This Article analyzes the diploma privilege from a historical and empirical perspective. Whereas courts and regulators maintain that bar examinations screen out incompetent practitioners, the legal profession formerly placed little emphasis on bar examinations and viewed them as superfluous for graduates of accredited law schools. The organized bar turned against the diploma privilege as the legal profession began to diversify, and some states abolished the diploma privilege specifically to block black law students from the profession. The notion that bar examinations ensure a base level of competence is a relatively recent construct. A few studies have suggested that attorneys who struggle on the bar examination are more likely to commit misconduct. However, drawing on cross-state attorney complaint and charge data as well as Wisconsin attorney disciplinary cases, I demonstrate that the bar examination requirement has no effect on attorney misconduct. The complaint rate against Wisconsin attorneys is similar to that of other jurisdictions, and Wisconsin attorneys are charged with misconduct less often than attorneys in most other states. Moreover, the rate of public discipline against Wisconsin attorneys who were admitted via the diploma privilege is the same as that of Wisconsin attorneys admitted via bar examinations. Bar examinations as currently constituted do little to advance public protection. A carefully drafted and enacted diploma privilege would comply with the Constitution’s Dormant Commerce Clause and would incentivize law schools to better prepare students for practice. States also have more direct means to address attorney misconduct than relying on ex ante measures such as bar examinations.
Instrumentation sensitivities for tower-based solar-induced fluorescence measurements

Abstract Solar-induced chlorophyll fluorescence (SIF) has been widely cited as a proxy for photosynthesis and is being incorporated as a common input in terrestrial primary productivity models. Though satellite-based SIF products show close relationships with terrestrial gross primary productivity (GPP), there is wide variability in the magnitude of published SIF retrievals made at intermediate scales. In a meta-analysis of the tower-based and airborne SIF literature, we found that mean SIF retrievals from unstressed vegetation spanned a wide range, from 0.041 mW m−2 nm−1 sr−1 to 14.8 mW m−2 nm−1 sr−1, with a majority of values falling below 4 mW m−2 nm−1 sr−1. We compiled information on reported spectrometer calibration procedures, hardware characterizations, and associated corrections from these same papers, and found inconsistent reporting on if and how key calibration methodology was performed. In order to quantify the importance of such methodological differences on final SIF retrievals made at a proximal scale, we performed radiometric calibrations and corrections for electronic dark current, detector noise, atmospheric O2 absorbance, and cosine corrector effects on three field-deployed spectrometers. We found dramatic changes in SIF retrieval magnitude before and after applying calibrations and corrections, as well as significant differences between instrument performance in the field and expected performance based on laboratory characterizations. Based on these tests, and on a Monte Carlo simulation of uncertainty estimates associated with each of these corrections, it is likely that calibration methodologies and hardware characterizations explain some of the observed variability in published SIF retrievals. This wide range in baseline SIF retrieval methodologies and resultant magnitudes severely limit researchers' ability to synthesize and advance the utility of SIF in modeling GPP across scales. Further, variability in calibration and correction methodology may explain the weak SIF-GPP relationship across studies at tower scales.
Leases and Sales: Ne'er or Where Shall the Twain Meet

For centuries, learned scholars and judges have expounded their views of the distinctions between sales and leases. The distinction has resulted in differential treatment of sales and leases in such areas as bankruptcy, tax, remedies on default, and filing requirements. Recently, several prominent scholars have suggested that the sale-lease distinction is meaningless. Professor Ayer has pondered over The Vacuity of the Sale/Lease Distinction, and his article in this issue further develops his thesis that the sale-lease distinction should be abandoned.
Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

Abstract Background SARS-CoV-2 infection is associated with thrombotic and microvascular complications. The cause of coagulopathy in the disease is incompletely understood. Methods A single-center cross-sectional study including 66 adult COVID-19 patients (40 moderate, 26 severe disease), and 9 controls, performed between 04/2020 and 10/2020. Markers of coagulation, endothelial cell function [angiopoietin-1,-2, P-selectin, von Willebrand Factor Antigen (WF:Ag), von Willebrand Factor Ristocetin Cofactor, ADAMTS13, thrombomodulin, soluble Endothelial cell Protein C Receptor (sEPCR), Tissue Factor Pathway Inhibitor], neutrophil activation (elastase, citrullinated histones) and fibrinolysis (tissue-type plasminogen activator, plasminogen activator inhibitor-1) were evaluated using ELISA. Tissue Factor (TF) was estimated by antithrombin-FVIIa complex (AT/FVIIa) and microparticles-TF (MP-TF). We correlated each marker and determined its association with severity. Expression of pulmonary TF, thrombomodulin and EPCR was determined by immunohistochemistry in 9 autopsies. Findings Comorbidities were frequent in both groups, with older age associated with severe disease. All patients were on prophylactic anticoagulants. Three patients (4.5%) developed pulmonary embolism. Mortality was 7.5%. Patients presented with mild alterations in the coagulogram (compensated state). Biomarkers of endothelial cell, neutrophil activation and fibrinolysis were elevated in severe vs moderate disease; AT/FVIIa and MP-TF levels were higher in severe patients. Logistic regression revealed an association of D-dimers, angiopoietin-1, vWF:Ag, thrombomodulin, white blood cells, absolute neutrophil count (ANC) and hemoglobin levels with severity, with ANC and vWF:Ag identified as independent factors. Notably, postmortem specimens demonstrated epithelial expression of TF in the lung of fatal COVID-19 cases with loss of thrombomodulin staining, implying in a shift towards a procoagulant state. Interpretation Coagulation dysregulation has multifactorial etiology in SARS-Cov-2 infection. Upregulation of pulmonary TF with loss of thrombomodulin emerge as a potential link to immunothrombosis, and therapeutic targets in the disease. Funding John Hopkins University School of Medicine.
Multi‐source mixing models to quantify food web sources and pathways

Summary 1 Biogeochemical tracers such as stable isotopes are often used to determine sources and pathways of organic matter through food webs, which may provide powerful indicators of environmental stress or insight into resource management issues. However, mixing models using such tracers are algebraically constrained and rarely attempted for more than two sources. This makes them of limited value for ecosystems that have numerous contributing sources. 2 We developed two complementary mixing models, SOURCE and STEP, which use linear programming techniques with multiple tracers, to estimate the dominant primary producer sources of consumers, and their diets and trophic levels, regardless of the number of sources and trophic steps. 3 SOURCE is used to estimate consumers’ direct and indirect uptake of autotrophic sources and their trophic levels. STEP calculates an estimate of a consumer's diet, which may include autotrophs and/or heterotrophs. 4 The two models were tested using simulated data sets of producer and consumer tracer values and then used with published δ13C, δ15N and δ34S data from a study tracing organic matter flows in a saltmarsh estuary. 5 SOURCE and STEP accurately estimated flows and trophic structures in the simulations, with average errors of 0·07–0·09 for SOURCE and 0·03–0·05 for STEP, depending on the number of tracers used. 6 We illustrate two resultant food webs for the saltmarsh estuary showing possible interpretations of the SOURCE and STEP estimates. 7 Synthesis and applications. SOURCE and STEP can be used with stable isotope data to estimate accurately consumers’ trophic levels, primary producer dependence and diets, even when the number of potential autotrophic sources or foods is larger than the number of tracers. SOURCE and STEP could be used to assess the roles played by individual species within food webs, to compare food webs across locations or over time, and to examine potential pollutant bioaccumulation in higher order consumers, among other potential applications. The s-plus code for both models is available at http://staff.washington.edu/lubetkin.
Cryogenic Recovery of Unquenchable High‐Pressure Samples Using a Multianvil Device

A simple modification has been made to the standard Walker-style 6-8 multianvil apparatus, to allow samples to be depressurized at low temperatures. This is done by introducing a coolant, in this case liquid nitrogen, into the sample area during decompression. Thus low-temperature recovery techniques, which have been used previously in a few instances in the diamond-anvil cell and piston-cylinder apparatus, have been extended to the multiple anvil, allowing large samples of some unquenchable phases to be recovered from high pressures. Two large (60 mg. each) samples of calcium hydroxide (Ca(OH) 2 ) and three samples of calcium deuteroxide (Ca(OD) 2 ), both in the unquenchable high pressure EuI 2 (baddeleyite-related) form, have been recovered from 9 GPa and 400 °C using this technique. The recovered samples are shown by Raman spectroscopy to retain the high pressure structure at 85 K. During heating at 10 K per minute, the material begins to revert to the low pressure portlandite phase at 223 K, and the reversion is complete by 275 K. This recovery technique can be used subject to certain kinetic conditions, but in general the outcome cannot be predicted and an experiment needs to be performed for each material of interest.
Navigation of Ground Vehicles Using Magnetic Field Variations

Inexpensive three-axis magnetometers can sense not just heading, but also variations in Earth's magnetic field. Combined with a magnetic field map, this information can be used for positioning. Pairing the three-axis magnetometer measurements with position information from a ground vehicle creates a magnetic field map containing the variation and localized perturbations in Earth's magnetic field as a function of position. A magnetometer and the magnetic field map can then be used for navigation. This paper describes how magnetometer measurements can be used to calculate a position update using three different likelihood functions, and it also demonstrates direct incorporation of magnetic field measurements into a map-matching particle filter. These algorithms were tested in three different vehicles under a variety of road conditions and demonstrated meter-level positioning when local magnetic field features are available. Overall the information is sufficient for road level navigation when used as the sole source of navigation information. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.