cssi/SciSciGPT-SciSciNet huggingface dataset:
Magnetic Resonance Imaging with Hyperpolarized Agents: Methods and Applications

In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into (1) a brief introduction, (2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, (3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, (4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study: (5) metabolic pathways in cancer and cardiac disease and (6) lung function in both pre-clinical and clinical research studies, concluding with (7) some future directions and challenges, and (8) an overall summary.
Fractal: An Execution Model for Fine-Grain Nested Speculative Parallelism

Most systems that support speculative parallelization, like hardware transactional memory (HTM), do not support nested parallelism. This sacrifices substantial parallelism and precludes composing parallel algorithms. And the few HTMs that do support nested parallelism focus on parallelizing at the coarsest (shallowest) levels, incurring large overheads that squander most of their potential.We present FRACTAL, a new execution model that supports unordered and timestamp-ordered nested parallelism. FRACTAL lets programmers seamlessly compose speculative parallel algorithms, and lets the architecture exploit parallelism at all levels. FRACTAL can parallelize a broader range of applications than prior speculative execution models. We design a FRACTAL implementation that extends the Swarm architecture and focuses on parallelizing at the finest (deepest) levels. Our approach sidesteps the issues of nested parallel HTMs and uncovers abundant fine-grain parallelism. As a result, FRACTAL outperforms prior speculative architectures by up to 88x at 256 cores.
Abstract WMP55: Risk Factors and Composite Risk Score for Predicting Stroke After Sepsis

Background and Purpose: Sepsis has been identified as a risk factor for stroke, however, the underlying mechanisms remain unclear and risk factors that may predispose a patient to an increased stro...
How perception generates, preserves, and mediates justification

Abstract“The Epistemic Significance of Perceptual Learning” defends the view that perceptual experiences generate justification in virtue of their presentational phenomenology, preserve past justification in virtue of the influence of perceptual learning on them, and thereby allow new beliefs formed on their basis to also be partly based on that past justification. “The Real Epistemic Significance of Perceptual Learning” mounts challenges to these three claims. Here we explore some avenues for responding to those challenges.
Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist Radiotracer in Schizophrenia

Abstract Background Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH. Methods D2/3 agonist positron emission tomography radiotracer [11C]N-propyl-norapomorphine ([11C]NPA) binding potential (BPND) was measured in 14 off-medication subjects with SCH and 14 matched HCs at baseline and after the administration of 0.5 mg kg–1 oral D-amphetamine. The amphetamine-induced change in BPND (ΔBPND) was calculated as the difference between BPND in the postamphetamine condition and BPND in the baseline condition and was expressed as a percentage of BPND at baseline. Results A trend-level increase was observed in comparing baseline [11C]NPA BPND (repeated-measures analysis of variance, F1,26 = 3.34, p = .08) between the SCH and HC groups. Amphetamine administration significantly decreased BPND in all striatal regions across all subjects in both groups. No differences were observed in [11C]NPA ΔBPND (repeated-measures analysis of variance, F1,26 = 1.9, p = .18) between HCs and subjects with SCH. Amphetamine significantly increased positive symptoms in subjects with SCH (19.5 ± 5.3 vs. 23.7 ± 4.1, paired t test, p Conclusions This study provides in vivo indication of a role for postsynaptic factors in amphetamine-induced psychosis in SCH.
An unusual reaction of a Reissert compound involving alkylation, rearrangement, SNAr and SET processes

Abstract Reaction of isoquinoline Reissert compound 1 with NaH and then isopropyl iodide in DMF at 22 °C led to four isolated products. Ketone 3 is the expected product of the well-known rearrangement of the intermediate Reissert anion. Cyano lactam 4 results from SNAr intramolecular displacement of the fluoride ion from the activated aroyl moiety of the anion. Isopropyl lactam 5 is proposed to result from a SET (single electron transfer) process via formation of the radical anion of 4, subsequent loss of the cyanide ion, and coupling of the resultant radical with isopropyl radicals formed via copper used to “stabilize” the alkyl iodide. The expected alkylated product 2 is also formed via a SET process involving electron transfer from the Reissert anion to 4, leading to the Reissert radical. Use of “non-stabilized” bromide or iodide led to 3 and 4, but did not produce 2 or 5.
Student documentation of multiple diagnoses in family practice patients using a handheld student encounter log

Patient encounter logs may provide an important early opportunity to assess beginning clinical students' attention to and experience with many medical problems. However, there are reasons to doubt the completeness of traditional paper logs. The family practice clerkship at Washington University in St. Louis has tried a series of structured paper and hand held computer logs in search of a format that permits students to completely document their patients' diagnoses. The clerkship introduced a Palm computer log, designed with PumaTech's Satellite forms (R), that uses patient demographics to select a diagnosis entry screen displaying many likely diagnoses as checkboxes. Additional drop lists and combinations of drop lists provide access to less common diagnoses. Students using this log document 2.4 problems per patient on average, and as many as 14 problems in a single patient. Differences between students and preceptors are readily apparent. It is now possible to prepare students to rotate with specific preceptors, and to identify or predict gaps in experience that deserve remedial intervention.
Multi-resident AFS: an adventure in mass storage

The Pittsburgh Supercomputing Center has been working to integrate distributed file system technology with hierarchical mass storage. We produced a system utilizing the Andrew File System that can be interfaced to many mass storage systems. We retained the semantics of AFS and compatibility with standard clients and servers. The architecture has a logical separation between the facility that provides the user interface and access semantics and the management of the storage systems that contain user data. Support for file level replication is provided for high availability to data in a fashion that is transparent to users. This system is called Multi-Resident AFS.
Technical Efficiency of Public Hospitals in Senegal: A Data Envelopment Analysis with an Estimated Case Mix Index

In sub-Saharan Africa, hospitals absorb the greatest proportion of total health resources according to the World health Organization. Senegal is no exception to this, out of the total government expenditure in the health sector, a third is absorbed by public hospitals and specialized health institutes on average each year. This heavy use of health resources by the hospitals relative to other public health providers raises questions about how efficiently those scarce resources are used. This study assesses the technical and scale efficiency of Senegalese public hospitals using Data Envelopment Analysis. For Senegal, I find that the public hospitals’ technical efficiency mean of 0.969 is higher than what was found for African hospitals in general but, the mean scale efficiency of 0.881 is very similar. However, Senegal has technically inefficient hospitals that could be using fewer inputs for the actual level of output they are producing and the possible savings in inputs are not trivial, especially concerning the number of physicians. To reduce the waste in inputs, I would recommend their redistribution through an upgrade of the top health centers in the country, particularly in the regions without a hospital, into public hospitals.
Sex‐biased gene expression in flowers, but not leaves, reveals secondary sexual dimorphism in Populus balsamifera

Because sexual dimorphism in plants is often less morphologically conspicuous than in animals, studies of sex-biased gene expression may provide a quantitative metric to better address their commonality, molecular pathways, consistency across tissues and taxa, and evolution. The presence of sex-biased gene expression in tissues other than the androecium or gynoecium, termed secondary sexual characters, suggests that these traits arose after the initial evolution of dioecy. Patterns of sequence evolution may provide evidence of positive selection that drove sexual specialization. We compared gene expression in male and female flowers and leaves of Populus balsamifera to assess the extent of sex-biased expression, and tested whether sex-biased genes exhibit elevated rates of protein evolution. Sex-biased expression was pervasive in floral tissue, but nearly absent in leaf tissue. Female-biased genes in flowers were associated with photosynthesis, whereas male-biased genes were associated with mitochondrial function. Sex-biased genes did not exhibit elevated rates of protein evolution, contrary to results from other studies in animals and plants. Our results suggest that the ecological and physiological constraints associated with the energetics of flowering, rather than sexual conflict, have probably shaped the differences in male and female gene expression in P. balsamifera.
βIV-spectrin regulates STAT3 targeting to tune cardiac response to pressure overload

Heart failure (HF) remains a major source of morbidity and mortality in the US. The multifunctional Ca2+/calmodulin-dependent kinase II (CaMKII) has emerged as a critical regulator of cardiac hypertrophy and failure, although the mechanisms remain unclear. Previous studies have established that the cytoskeletal protein βIV-spectrin coordinates local CaMKII signaling. Here, we sought to determine the role of a spectrin-CaMKII complex in maladaptive remodeling in HF. Chronic pressure overload (6 weeks of transaortic constriction [TAC]) induced a decrease in cardiac function in WT mice but not in animals expressing truncated βIV-spectrin lacking spectrin-CaMKII interaction (qv3J mice). Underlying the observed differences in function was an unexpected differential regulation of STAT3-related genes in qv3J TAC hearts. In vitro experiments demonstrated that βIV-spectrin serves as a target for CaMKII phosphorylation, which regulates its stability. Cardiac-specific βIV-spectrin-KO (βIV-cKO) mice showed STAT3 dysregulation, fibrosis, and decreased cardiac function at baseline, similar to what was observed with TAC in WT mice. STAT3 inhibition restored normal cardiac structure and function in βIV-cKO and WT TAC hearts. Our studies identify a spectrin-based complex essential for regulation of the cardiac response to chronic pressure overload. We anticipate that strategies targeting the new spectrin-based "statosome" will be effective at suppressing maladaptive remodeling in response to chronic stress.
A [11C] CO dispensing system for rapid screening of carbonylation reactions

[11 C] CO is a highly versatile synthon that allows for labeling at carbonyl positions of many molecules by means of transition metal-mediated carbonylation reactions. The intrinsic complexity of carbonylation reactions often requires tedious screening of reaction conditions for obtaining satisfying yields. Herein, a [11 C] CO dispending system for performing multiple reactions with a single batch of cyclotron-produced [11 C]CO2 is described. This semiautomated setup allows for more rapid and efficient screening of reactions and reaction conditions compared with the traditional "one beam for one reaction" strategy.
Long-Range Electric Field Control of Permalloy Layers in Strain-Coupled Composite Multiferroics

Strain-coupled composite multiferroics, comprised of magnetostrictive and piezoelectric materials, promise tunable control of magnetism in applications such as rf resonators, sensors, and energy harvesters. Using polarized neutron reflectometry, the authors demonstrate that magnetostrictive and weakly magnetostrictive materials in a multilayer can be strain-coupled to an electric field over large length scales that enable designer functionality across a range of device applications.
Assessment of Cognitive Impairment in Patients with Chronic Obstructive Pulmonary Disease Using the Rapid Cognitive Screen.

To determine the prevalence of cognitive impairment in chronic obstructive pulmonary disease (COPD) patients using the Rapid Cognitive Screen (RCS). Cross sectional study. A total of 106 men and women with COPD 50 years of age or older. Setting: Pulmonary ambulatory clinic in a tertiary academic center in St. Louis, Missouri, USA. We enrolled patients with COPD who completed the RCS tool. Patients were classified as having normal cognition, mild cognitive impairment (MCI), or dementia if they scored ≥ 8, 6–7, or ≤ 5, respectively. The prevalence of each category was measured, and patients’ baseline characteristics were compared. One hundred and six patients completed the RCS. Of those, 36 (33.9%) patients scored ≤ 5 on the RCS, 33 (31.1%) scored 6 or 7, and 37 (34.9%) scored ≥ 8. The prevalence of dementia, MCI, and normal cognition were 33.9%, 31.1%, and 34.9%, respectively. Baseline lung function was not different between patients with normal cognition and those with abnormal cognition (FEV1 1.53 ± 0.39 vs 1.45 ± 0.32 L). In patients with abnormal cognition, there was no difference in patients’ characteristics between patients with MCI or dementia. Cognitive impairment is highly prevalent in patients with COPD. RCS successfully identified cognitive impairment in COPD. We recommend performing RCS in patients with COPD routinely.
INTEGRATED CHANGE MANAGEMENT AND PROJECT MANAGEMENT STRATEGIC FRAMEWORK

The purpose of this conceptual paper was to provide key details for how practitioners can build a bridge between the Change Management (CM) and the Project Management (PM) tasks and roles in organizations. This paper is a conceptual paper discussing the integration of CM and PM in organizations and provides one approach to utilize this integration in a practical work environment. This approach was both specific and replicable in most business environments where projects are the key vehicle in delivering changes across the organization. This paper illustrated one way to integrate change through a framework of utilizing existing project team members in the role of project “change lead”; operational leaders in a change-champion capacity; and change-management experts in a centralized role to consult, control, and ensure consistency throughout the change journey. This concept is one strategic approach to CM and PM integration were created to utilize people as a resource in change projects. The approach adds value (1) to PMs needing assistance in CM integration and (2) to CMs integrating change projects within their organizations. Keywords Change Champion, Change Management, Project Change Lead, project Management CITATION: Dicianno, J. E., & Gigliotti, A. (2018). Integrated change management and project management strategic framework. The Strategic Journal of Business & Change Management, 5(4), 2189 - 2198.
2013 Vehicle Technologies Market Report

This is the fifth edition of this report, which details the major trends in U.S. light-duty vehicle and medium/heavy truck markets as well as the underlying trends that caused them. This report is supported by the U.S. Department of Energy s (DOE) Vehicle Technologies Office (VTO), and, in accord with its mission, pays special attention to the progress of high-efficiency and alternative-fuel technologies. After opening with a discussion of energy and economics, this report features a section each on the light-duty vehicle and heavy/medium truck markets, and concluding with a section each on technology and policy. The first section on Energy and Economics discusses the role of transportation energy and vehicle markets on a national (and even international) scale. For example, Figures 12 through 14 discuss the connections between global oil prices and U.S. GDP, and Figures 21 and 22 show U.S. employment in the automotive sector. The following section examines Light-Duty Vehicle use, markets, manufacture, and supply chains. Figures 24 through 51 offer snapshots of major light-duty vehicle brands in the U.S. and Figures 56 through 64 examine the performance and efficiency characteristics of vehicles sold. The discussion of Medium and Heavy Trucks offers information on truck sales (Figures more » 73 through 75) and fuel use (Figures 78 through 81). The Technology section offers information on alternative fuel vehicles and infrastructure (Figures 84 through 95), and the Policy section concludes with information on recent, current, and near-future Federal policies like the Corporate Average Fuel Economy standard (Figures 106 through 110). In total, the information contained in this report is intended to communicate a fairly complete understanding of U.S. highway transportation energy through a series of easily digestible nuggets. « less
Descriptive Inquiry: Care of the Principal Self.

ABSTRACTThis paper investigates how principals can be supported in their work as teacher leaders. My focus is on how principals can help teachers respond ethically to classroom challenges. I argue that in aiding teachers, school leaders themselves need support and ongoing development. I turn to the care of the self to conceptually explore ethical self-cultivation. I then argue that a practice, Descriptive Inquiry, serves as a way for principals to care for themselves. To make this argument, I draw on a qualitative study of four long-term elementary school principals.
Transcriptomic Response to Feeding and Starvation in a Herbivorous Dinoflagellate

Grazing by heterotrophic protists influences plankton population dynamics, community composition, and the flux of carbon through marine planktonic food webs. To gain insight into the molecular underpinnings of grazing in dinoflagellates, a group of important heterotrophic protists, we used an RNA-seq approach to investigate the transcriptomic response of Oxyrrhis marina under fed and starved treatments with three different phytoplankton prey (Isochrysis galbana and two strains of Heterosigma akashiwo). In response to fed and starved conditions, 1,575 transcripts were significantly differentially expressed in O. marina. Fed O. marina cells upregulated transcripts involved in the synthesis of essential fatty acids and storage carbohydrates suggesting that the predator was food satiated and excess glucose was being stored as an energy reserve. Transcripts encoding voltage-gated ion channels were also upregulated during grazing, and they are known to be involved in the detection of mechanical stimuli and the regulation of swimming behavior in several eukaryotic protists. Fed O. marina cells upregulated kinases, which can dictate cell shape changes and may be associated with phagocytosis. During starvation, upregulated O. marina transcripts included those involved in the degradation of energy-storage molecules like glucan 1,4 alpha-glycosidase and those involved in antioxidant activities and autophagy, like acid ceramidase that are associated with the digestion of polar lipids present in cell membranes. Starved O. marina also upregulated transcripts with high similarity to proton pumping proteorodopsins suggesting that this heterotrophic protist may supplement its energy requirement during starvation with a light harvesting mechanism. Although herbivorous grazing is a pivotal transformation in the C cycle, logistical constraints limit our investigations of environmental and biological drivers. The molecular signals identified here provide new insights into the metabolic regulation of feeding and starvation in marine heterotrophic protists and can fuel hypothesis-driven research into predators' metabolic response to prey availability.
Is topical treatment effective for psoriasis in patients who failed topical treatment

Objectives: To determine if resistance to topical treatments can be overcome under conditions promoting adherence.Materials and Methods: Twelve psoriasis patients treated with topical 0.25% desoxim...
Unified cochlear model for low- and high-frequency mammalian hearing

The spatial variations of the intricate cytoarchitecture, fluid scalae, and mechano-electric transduction in the mammalian cochlea have long been postulated to provide the organ with the ability to perform a real-time, time-frequency processing of sound. However, the precise manner by which this tripartite coupling enables the exquisite cochlear filtering has yet to be articulated in a base-to-apex mathematical model. Moreover, while sound-evoked tuning curves derived from mechanical gains are excellent surrogates for auditory nerve fiber thresholds at the base of the cochlea, this correlation fails at the apex. The key factors influencing the divergence of both mechanical and neural tuning at the apex, as well as the spatial variation of mechanical tuning, are incompletely understood. We develop a model that shows that the mechanical effects arising from the combination of the taper of the cochlear scalae and the spatial variation of the cytoarchitecture of the cochlea provide robust mechanisms that modulate the outer hair cell-mediated active response and provide the basis for the transition of the mechanical gain spectra along the cochlear spiral. Further, the model predicts that the neural tuning at the base is primarily governed by the mechanical filtering of the cochlear partition. At the apex, microscale fluid dynamics and nanoscale channel dynamics must also be invoked to describe the threshold neural tuning for low frequencies. Overall, the model delineates a physiological basis for the difference between basal and apical gain seen in experiments and provides a coherent description of high- and low-frequency cochlear tuning.
Lewis acid assisted cyclization of arylcyanoguanidines to 2,4‐diaminoquinazolines

The mild preparation of N-cyano-N-(1-H-indol-5-yl)guanidine and its cyclization to 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline is described. Whereas previously reported methods of cyclization employed high temperatures to effect ring closure, we found that certain Lewis acids, such as boron trifluoride etherate, induce cyclization at moderate temperatures.
Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison.

Abstract Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81–83%) than mice (59–63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.
Family Discussions of Early Childhood Social Transitions.

Objective An increasing number of children are socially transitioning to live as their identified genders rather than their assigned sexes, yet little empirical work has examined the decision-making process surrounding social transitions. We aimed to understand (1) why parents and their gender nonconforming children do and do not consider social transitions and (2) whether families discuss social transitions both before and after initial social transitions. Methods Studies 1 and 2 involved telephone interviews of parents of socially transitioned transgender children (N=60) and gender nonconforming children who were not socially transitioned (N=60), respectively. Study 3 involved an online survey of 266 parents of socially transitioned transgender children. Results Parents of socially transitioned transgender children (Study 1) and parents of gender nonconforming children who are not socially transitioned (Study 2) often reported that their children had led the decision to transition or not. Most parents of gender nonconforming children who had not transitioned had discussed transitioning (Study 2) and most parents of socially-transitioned transgender children reported discussing the option of future re-transitions (Study 3). Conclusions Parents often report that they and their children are discussing social transitions, a process that children are leading. In contrast to possible concerns about discussing transitions, our results suggest that many families openly discuss the possibility of their children transitioning (or re-transitioning), yet these discussion do not inevitably lead to an imminent transition.
Is More Better? Divide between Retailer's and Manufacturers' Preferences for Reviews and Review Monetization

Research on online product reviews has examined a variety of issues ranging from reviewers' motivation to write reviews to impact of reviews on product sales. Implicit in a large number of studies in this research stream is the notion that more reviews is better for sellers and consumers. However, it is unclear whether a retailer, who often controls the review platform, and manufacturers, whose products are being reviewed, prefer more reviews to less. Using a game theoretical model of a context in which a retailer sells competing products from two manufacturers and consumers are uncertain about product qualities, we show that the retailer's and the manufacturers' preferences regarding the number of reviews are not always aligned. If the reviews are costless, then additional reviews benefit the retailer, but manufacturers are hurt by additional reviews when the number of reviews exceeds a threshold. Moreover, if the consumers' own uncertainty about product qualities is not too high, then the manufacturers do not prefer to have reviews at all. On the other hand, if the retailer incurs a sufficiently high cost to generate reviews, he may prefer to have fewer reviews than manufacturers. We show that the divide between the retailer's and the manufacturers' preferences can induce the retailer to monetize reviews by charging a fee to manufacturers in return for a guarantee on the number of reviews that would be made available in the review platform. The retailer's revenue from such monetization follows a U-shape with respect to the cost of generating reviews as well as the extent to which reviews can reveal true product quality, suggesting that the product type and review platform design play a significant role in the attractiveness of review monetization for the retailer. The revenue from "selling" reviews to manufacturers does not exceed the cost of generating reviews, implying the retailer's benefit from reviews, even when they can be monetized, is driven by reviews' positive impacts on the retailer's core business of selling products to consumers. The findings provide economic insights into the nascent efforts of Amazon to monetize reviews through programs such as Amazon Vine.
Deuteriodifluoromethylation and gem-Difluoroalkenylation of Aldehydes Using ClCF 2 H in Continuous Flow

The deuteriodifluoromethyl group (CF2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF2 H) gas in the continuous flow deuteriodifluoromethylation and gem-difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D2 O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product.
Grammatical number is sufficiently explained by communicative needs.

Franzon, Zanini and Rugani offer a useful clarification of their viewpoint expressed in earlier work. (Franzon et al., 2020; Franson et al. 2019) Their account might be encapsulated as follows: A) ...
10-Year Breast Cancer Outcomes in Women ≤35 Years of Age.

Purpose Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy. Methods and Materials Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan–Meier methodology. Results A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P Conclusion Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.
Group Dynamics across Interaction Modes in L2 Collaborative Wiki Writing

Abstract Understanding group dynamics is crucial in L2 collaborative writing, as it impacts linguistic negotiations and text quality. Previous studies have mostly identified a group’s predominant interaction pattern in relation to members’ task contributions (equality) and their engagement with each other’s contributions (mutuality). However, the convergent nature of wikis incorporates multiple interaction modes within the same platform (e.g., discussion mode and edit mode), which afford varying degrees of transparency. This study examined the fluidity of interaction patterns exhibited by four groups of L2 writers in the discussion and edit modes as they co-authored short stories on a wiki. Results indicate that while mutuality was relatively stable across interaction modes, all groups displayed higher equality in the discussion than in the edit mode. Writers also seemed to converge the two modes to navigate authorship and achieve communicative purposes. Furthermore, the study explored connections between interaction patterns and text quality. Groups exhibiting high mutuality fully developed their plots and wrote longer stories, but there was no effect on accuracy, stylistics or genre appropriateness. The findings underscore the fluidity of interaction patterns across interaction modes with varying levels of transparency and highlight the importance of mutuality as a driver of text quality.
Partisan Politics and Income Tax Rates

With income tax reform dominating so much of the current political discourse, now is an optimal time for tax scholars to reflect on the lessons and trends from a century of legislative tinkering with the primary revenue-generating device in the United States. Tax rate changes do not occur in a vacuum, and this article explores one increasingly prominent and often overlooked ingredient in the mixture of variables that can produce or inhibit tax reform ― partisan politics. It does so by comparing individual income tax rates with partisan control of federal political bodies. This article reviews majority party status in the House of Representatives and the Senate, and control of the presidency at times of revisions to top marginal tax rates applicable to various income groups, and notes larger rate trends in the parties’ respective eras of most significant influence. Despite the limitations inherent in isolating a single influential factor, the data analyzed in this article provides strong support for the following trends: higher income earners are the tax rate battleground for party policy implementation; a vast political mandate represented by control of the House, Senate, and presidency is usually necessary to accomplish significant rate revisions; when a sufficient political mandate is achieved, the parties’ implementation of rate changes follows their respective rhetorical associations; and in the end, absent armed conflict or economic crisis, sizeable rate changes are exceptionally rare. These extractions from a century of legislative maneuvers bring scholars closer to unearthing the political recipe for tax rate reform, and accordingly, to a fuller understanding of the necessary components of tax policy implementation.
Preoperative Opioid Use in Patients Undergoing Common Hand Surgeries.

Background:The objectives of this study were to determine the baseline patient characteristics associated with preoperative opioid use and to establish whether preoperative opioid use is associated...
A Farewell to Harms: Presuming Irreparable Injury in Constitutional Litigation

Although it is an essential element to obtaining injunctive relief, most federal circuit courts have held that irreparable injury can be presumed in constitutional cases. The Supreme Court has not addressed in the constitutional context but it has disapproved of the practice of presuming irreparable harm for federal statutory claims. This article argues that the presumption is improper. The history of the injunctive remedy in this country suggests that irreparable injury is an essential element of proof that should be applied in all cases. Indeed, although constitutional rights are of paramount importance in our legal system, the fact that those rights are implicated has never been justification for courts to presume an entitlement to a damages remedy. Courts have come to accept harmless constitutional wrongs in criminal proceedings and in civil damages suits, as the numerous nominal damages recoveries in Section 1983 cases can attest. They should not be reluctant when injunctive relief is sought to acknowledge the reality that some constitutional infractions produce no serious or non-compensable harm. A plaintiff who cannot show irreparable harm or prove damages can always obtain a declaratory judgment. Courts, however, must endeavor to make that remedy a satisfactory alternative to the injunction by abandoning their reluctance to award attorneys’ fees to plaintiffs who obtain only declaratory relief. Presuming irreparable harm encourages plaintiffs to seek preliminary injunctions and it is far less preferable for constitutional questions to be resolved on preliminary injunction motions than at trial or on summary judgment. Preliminary injunction determinations are provisional and tentative, often the product of an incomplete evidentiary record generated at abbreviated and rushed hearings. They are subject to the least rigorous appellate standard. Final judgments on constitutional questions, by contrast, produce definitive holdings and are subject to non-deferential appellate review. Eliminating the presumption will produce far better decision-making in constitutional cases.
Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

Previously, we demonstrated low-dose antithymocyte globulin (ATG) and granulocyte colony-stimulating factor (GCSF) immunotherapy preserved C-peptide for 2 years in a pilot study of patients with established type 1 diabetes (n = 25). Here, we evaluated the long-term outcomes of ATG/GCSF in study participants with 5 years of available follow-up data (n = 15). The primary end point was area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test. After 5 years, there were no statistically significant differences in AUC C-peptide when comparing those who received ATG/GCSF versus placebo (P = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over 5 years, accounting for differing trends between groups, was applied to recategorize responders (n = 9) and nonresponders (n = 7). ATG/GCSF reponders demonstrated nearly unchanged HbA1c over 5 years (mean [95% CI] adjusted change 0.29% [–0.69%, 1.27%]), but the study was not powered for comparisons against nonresponders 1.75% (–0.57%, 4.06%) or placebo recipients 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow-up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.
Early Educators' Collective Workplace Stress as a Predictor of Professional Development's Impacts on Children's Development.

Although professional development is widely used to improve the impacts of early childhood education, little is known about the conditions under which such interventions promote child outcomes. This study applies newly developed methods for quantifying intervention impact heterogeneity to understand whether educators' collective workplace stress moderates professional development's impacts on children's language and literacy skills, executive functioning, and learning behaviors. Within a sample of 406 children from the National Center for Research on Early Childhood Education Professional Development Study (Mage = 4.17; 50% female; 50% Black, 32% Latinx, 11% White), professional development positively impacted child outcomes in centers where educators collectively reported high workplace stress but negatively impacted child outcomes in centers where educators collectively reported low workplace stress.
Magnetic resonance imaging findings following button battery ingestion

Lithium button battery ingestions have been increasing in frequency since the early 2000s and can develop severe and sometimes fatal complications from caustic injury even after rapid battery removal. To aid in clinical decision-making, we began obtaining magnetic resonance imaging (MRI)/MR angiography in these patients. Our goal was to review MRI/MR angiography imaging in button battery ingestion cases and compare with other imaging, clinical data and outcomes in these patients. In this retrospective institutional-review-board-approved study, we reviewed all button battery ingestion cases with MRI from April 2012 to September 2018. Clinical data, endoscopic findings and all imaging studies were rereviewed. MRIs were evaluated for inflammation, blooming artifact and complications including vascular injury, tracheoesophageal fistula, esophageal perforation and spondylodiscitis, and compared to endoscopy, esophagram and bronchoscopy. Twenty-three patients with button battery ingestions had a total of 51 MRI/MR angiograms. Seventy percent of the cohort was male with a median age of 2 years (range: 0.94–17 years). Severe complications were found in 48% of patients (11/23), including esophageal perforation (n=11), tracheoesophageal fistula (n=3) and spondylodiscitis (n=1). No patients had vascular injury. Cervical location of the battery was significantly associated with severe complications (10/11 cases). The length of the blooming artifact was greater than 2 cm in those with severe complications and, in most cases, <2 cm in those without severe complications. All complications were seen on initial screening MR exam with serial exams showing decreased inflammation. MRI/MR angiography can provide valuable information about complications, including esophageal perforation, tracheoesophageal fistula and spondylodiscitis. Decreasing inflammation surrounding the esophagus and vasculature is believed to be clinically reassuring and aids in managing button battery ingestion patients.
Alpha-Synuclein-induced DNA Methylation and Gene Expression in Microglia.

Abstract Synucleinopathy disorders are characterized by aggregates of α-synuclein (α-syn), which engage microglia to elicit a neuroinflammatory response. Here, we determined the gene expression and DNA methylation changes in microglia induced by aggregate α-syn. Transgenic murine Thy-1 promoter (mThy1)-Asyn mice overexpressing human α-syn are a model of synucleinopathy. Microglia from 3 and 13-month-old mice were used to isolate nucleic acids for methylated DNA and RNA-sequencing. α-Syn-regulated changes in gene expression and genomic methylation were determined and examined for functional enrichment followed by network analysis to further elucidate possible connections within the data. Microglial DNA isolated from our 3-month cohort had 5315 differentially methylated gene (DMG) changes, while RNA levels demonstrated a change in 119 differentially expressed genes (DEGs) between mThy1-Asyn mice and wild-type littermate controls. The 3-month DEGs and DMGs were highly associated with adhesion and migration signaling, suggesting a phenotypic transition from resting to active microglia. We observed 3742 DMGs and 3766 DEGs in 13-month mThy1-Asyn mice. These genes were often related to adhesion, migration, cell cycle, cellular metabolism, and immune response. Network analysis also showed increased cell mobility and inflammatory functions at 3 months, shifting to cell cycle, immune response, and metabolism changes at 13 months. We observed significant α-syn-induced methylation and gene expression changes in microglia. Our data suggest that α-syn overexpression initiates microglial activation leading to neuroinflammation and cellular metabolic stresses, which is associated with disease progression.
Identification and expression profiling of blood-brain barrier membrane proteins

Blood-brain barrier (BBB) membrane proteins play crucial roles in the proper functioning of the BBB as well as in disease progression. Previously, we developed a novel approach for identifying membrane proteins expressed at the BBB, which we referred to as multiplex expression cloning. In this study, the proteome coverage of the multiplex expression cloning approach was expanded to allow the identification of a total of 30 BBB membrane proteins that are diverse in function and abundance. To unveil those membrane proteins that are enriched at the BBB and hence partially responsible for some of its unique characteristics, the transcript abundance levels for all 30 BBB membrane proteins were compared with those found in microvessels derived from lung, liver, heart, and kidney. Such quantitative PCR profiling of RNA samples from laser capture microdissected microvessels revealed that the transcripts for five membrane proteins, namely Lutheran glycoprotein, carbonic anhydrase IV, uncoupling protein 2, podocalyxin, and solute carrier family 38, member 5, were BBB selective, in that expression was elevated in brain microvessels when compared with all of the vascular beds tested. Many other membrane protein transcripts, whereas not as BBB-restricted, showed selective expression within subsets of tissues indicating other potential parallels and contrasts between vascular beds in the body. The identification of BBB membrane proteins could help better understand the molecular mechanisms responsible for BBB function and those with selective expression may have utility for BBB-targeted therapies.
An x-ray crystallographic study of ceruloplasmin. Determination of molecular weight.

Human ceruloplasmin crystallizes in the tetragonal space group I4 with a = b = 268 A and c = 129 A. The asymmetric unit consists of two molecules of ceruloplasmin of molecular weight 132,000. Taken in conjunction with the published value for the total protein-bound copper, these results indicate that there are 6 copper atoms in each ceruloplasmin molecule.