cssi/SciSciGPT-SciSciNet huggingface dataset:
Legislating Morality? The Tax Professional's Duty to the Tax System Reconsidered

Should tax professionals owe a duty (or a greater duty) to the tax system during a period of reduced IRS enforcement activities? If there is a special duty owed by tax professionals to the tax system, it will affect how these professionals interact (or should interact) with the IRS. Also, any such special duty should be clear, firmly established, normative, and feasible for tax professionals to comply. This article maintains that this has not been the case and that has led to the current crisis in investor confidence in the stock market and it has undermined the federal income tax system. The conflict between the ABA and the IRS over whether the filing of a tax return is adversarial has been a contributing factor to the current crisis. Until this conflict is resolved, the article argues there can be no meaningful duty to the tax system. One problem is that the accuracy related penalty provisions allow tax practitioners to resolve ambiguities in a return position in their client's favor without disclosure to the IRS. Thus, the tax system has encouraged the reporting of aggressive return positions. Another problem has been that the practitioner's reporting standard has been a higher standard than the taxpayer's reporting standard, and this has created conflicts of interest between the practitioner and the client because the practitioner is sometimes ethically obligated to recommend disclosure even though the client is not legally required to disclose, and even though disclosure may not protect the client from penalty. Yet another problem is the fact that there is some question about whether the accuracy related penalties establish a normative standard to which tax practitioners must adhere. The article reviews the debate over this issue and raises additional arguments why the penalty may not be regarded as normative. The article explores the potential factors that may have contributed to the spate of corporate accounting scandals and abusive tax avoidance transactions. It also discusses pending legislation that proposes new, increased accuracy-related penalties and greater disclosure. The article points out problems associated with this proposed legislation, but notes that if enacted, this legislation should bring an end to the debate over the tax professional's duty to the system because there will be fewer opportunities for tax practitioner's to use their discretion with respect to aggressive return positions.
Deliberative Democracy's Religion Problem

Deliberative democracy has a religion problem. The shared perspective called for by deliberative approaches coexists uneasily with the religious language and activism in U.S. politics today. The solution among deliberative theorists has been to argue that citizens should refrain from appealing to religious reasons in public. This paper argues that deliberative democracy's religion problem is of its own making, stemming from the way that it conceptualizes "religion." Theories of deliberative democracy understand religion as essentially apolitical and ahistorical, consisting primarily of assent to a set of beliefs. Religion is imagined as an autonomous area of life that appears as an occasional interloper on politics, rather than as something that is fundamentally constituted by and through politics. Deliberative theorists are then inevitably surprised and frustrated by the predictable "return" of religion and the failure of religiously-based political speech and action to fit their standards of legitimacy. I argue that understanding religion in terms of "tradition" allows a recognition of its political and historical dimensions, and that this conception fits within a deliberative framework. In other words, the religion problem does not mean that theories of deliberative democracy must be abandoned. Instead, they already have the resources within them to recognize and include religious language and activism as part of the deliberative process.
Factors in oral contraception related hypertension.

Essential patient data are tabulated for 13 patients who became hypertensive after using oral contraceptives and were seen during a 2 1/2-year period. All the contraceptives the patients were using contained mestranol as the estrogenic component. Possibly all the women had some degree of underlying kidney pathology which made them sensitive to the aldosterone-elevation effect of the oral contraceptives. It is suggested that from an individual hypertensive patient standpoint this reaction should be kept in mind especially in women 30 years of age or older.
The Role of Daylighting in Skilled Nursing Short-Term Rehabilitation Facilities.

Objective:The aim of this study is to investigate the best placement of windows in short-term rehabilitation facilities in terms of daylighting and outdoor views by exploring the impact of windows ...
Understanding the effects of preorganization, rigidity, and steric interactions in synthetic barbiturate receptors.

Synthetic barbiturate receptors have been utilized for many applications due to their high binding affinities for complementary guests. Although interest in this class of receptors spans from supramolecular to materials chemistry, the effects of receptor steric bulk and preorganization on guest binding affinity has not been studied systematically. To investigate the roles that steric bulk and preorganization play in guest binding, we prepared a series of 12 deconstructed Hamilton receptors with varying degrees of steric bulk and preorganization. Both diethylbarbital and 3-methyl-7-propylxanthine were investigated as guests for the synthetic receptors. The stoichiometry of guest binding was investigated using Job plots for each host–guest pair, and 1H NMR titrations were performed to measure the guest binding affinities. To complement the solution-state studies, DFT calculations at the B3LYP/6-31+G(d,p) level of theory employing the IEF-PCM CHCl3 solvation model were also performed. Calculated guest bindin...
Why are rods more sensitive than cones

One hundred and fifty years ago Max Schultze first proposed the duplex theory of vision, that vertebrate eyes have two types of photoreceptor cells with differing sensitivity: rods for dim light and cones for bright light and colour detection. We now know that this division is fundamental not only to the photoreceptors themselves but to the whole of retinal and visual processing. But why are rods more sensitive, and how did the duplex retina first evolve? Cells resembling cones are very old, first appearing among cnidarians; the emergence of rods was a key step in the evolution of the vertebrate eye. Many transduction proteins have different isoforms in rods and cones, and others are expressed at different levels. Moreover rods and cones have a different anatomy, with only rods containing membranous discs enclosed by the plasma membrane. These differences must be responsible for the difference in absolute sensitivity, but which are essential? Recent research particularly expressing cone proteins in rods or changing the level of expression seem to show that many of the molecular differences in the activation and decay of the response may have each made a small contribution as evolution proceeded stepwise with incremental increases in sensitivity. Rod outer-segment discs were not essential and developed after single-photon detection. These experiments collectively provide a new understanding of the two kinds of photoreceptors and help to explain how gene duplication and the formation of rod-specific proteins produced the duplex retina, which has remained remarkably constant in physiology from amphibians to man.
Spl Phosphorylation Induced by Serum Stimulates the Human α2(I) Collagen Gene Expression

Serum has been known to stimulate collagen production by dermal fibroblasts. As part of an ongoing study of the molecular mechanisms of collagen production, we have investigated transcriptional regulation of the human α2(I) collagen gene by serum in human dermal fibroblasts. Serum responsive elements were mapped by deletion analysis between bp -353 and -264, and between -148 and -108 in the α2(I) collagen promoter. Further functional analysis of the α2(I) collagen promoter containing various substitution mutations revealed that serum stimulation of this promoter is mediated equally by a GC-rich region located between bp -303 and -271 and by the TCCTCC motif located between bp -123 and -128, both of which constitute binding sites for transcription factor Spl and Sp3. No differences were observed in electrophoretic mobility shift assays between unstimulated and serum stimulated fibroblasts. The Spl inhibitor mithramycin blocked stimulation of the α2(I) collagen promoter activity by serum. Furthermore, immunoprecipitation analysis showed that serum stimulation increased Spl phosphorylation. In conclusion, this study characterized response elements that mediate serum stimulation of the human α2(I) collagen promoter and suggests that serum stimulation was mediated via Sp1/Sp3 binding sites in this promoter.
Abstract 228: Tumor suppressor functions of BNIP3 and mitophagy in pancreatic ductal adenocarcinoma

The role of mitochondrial dysfunction in cancer is an emerging research field fuelled by the growing realization that mitochondrial dynamics are subject to oncogenic control, with mitochondrial biogenesis and mitophagy in particular modulated directly or indirectly by key oncogenes (c-Myc, B-Raf, K-ras) and tumor suppressors (p53, pRB). Work from our lab has focused on understanding how defects in mitophagy influence tumorigenesis with a particular focus on how BNIP3 loss during tumor progression influences disease outcome. BNIP3 functions as a dimer at the outer mitochondrial membrane to target mitochondria for degradation at the autophagolysosome through its interaction with processed LC3 at nascent phagophores. BNIP3 is a transcriptional target of HIF-1, E2F and FoxO3A transcription factors and is induced by activated Ras and suppressed by the RB and p53 tumor suppressors. Various studies have shown BNIP3 expression to be induced at early stages of human cancers and then lost as cancers progress to malignancy. In particular, epigenetic silencing of BNIP3 in human pancreas cancer has been correlated with reduced median survival. However, the mechanisms by which loss of BNIP3 may be contributing to cancer progression are not well delineated and a better understanding of how BNIP3-dependent mitophagy modulates pancreatic cancer in particular could provide new insight to the development of this deadly disease. We set out to examine how loss of BNIP3 affects the progression of pancreatic ductal adenocarcinoma using human cell lines and genetically engineered mouse models. We show that loss of BNip3 markedly accelerates tumor initiation and progression to invasive PDAC in the Pdx1-Cre;LSL-KRasG12D mouse model with metastases to the liver and lungs evident in BNip3 null mice but not in age-matched wild-type mice. Supporting a role for BNIP3 in suppressing pancreatic tumorigenesis, we also showed that re-expression of exogenous BNIP3 in Miapaca-2 cells (in which endogenous BNIP3 is silenced) resulted in reduced growth while knockdown of BNIP3 in CFPAC1 cells (that express BNIP3) promotes cell growth. Work described here examines the underlying mechanisms explaining these tumor suppressor functions of BNIP3 in pancreatic ductal adenocarcinoma. Citation Format: Aparajita H. Chourasia, Maya Z. Springer, Kay F. Macleod. Tumor suppressor functions of BNIP3 and mitophagy in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 228.
Assessing Individual Health Insurance Coverage and Utilization Before and After the Patient Protection and Affordable Care Act

The adoption of the Patient Protection and Affordable Care Act PPACA in 2010 with the intent to improve the U.S. health care delivery system by expanding health insurance coverage and controlling health care costs has generated intense debate regarding its implementation. Marketplaces known as insurance exchanges have been established to provide coverage for Americans who otherwise could not get affordable health care benefits. These exchanges have been plagued with financial losses and other challenges leading to several large insurance providers discontinuing participation in the program. There are many possible remedies under consideration to make the program work better. This research seeks to support program evaluation as well as potential modifications to the law by providing baseline data to compare access and costs in states with state-based exchanges compared to states with federal exchanges. The authors perform an analysis by state for the years 2012 and 2013 pre-PPACA implementation using data from the Current Population Survey U.S. Census as well as de-identified claims data from Inovalon, Inc.
Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms

Abstract Objective Medicare studies have shown increased perioperative mortality in women compared with men following endovascular and open abdominal aortic aneurysm (AAA) repair. However, a recent regional study of high-volume centers, adjusting for anatomy but limited in sample size, did not show sex to be predictive of worse outcomes. This study aimed to evaluate sex differences after intact AAA repair in a national clinical registry. Methods The targeted vascular module of the National Surgical Quality Improvement Program was queried to identify patients undergoing endovascular aneurysm repair (EVAR) or open repair for intact, infrarenal AAA from 2011 to 2014. Univariate analysis was performed using the Fisher exact test and Mann-Whitney test. Multivariable logistic regression was used to account for differences in comorbidities, aneurysm details, and operative characteristics. Results We identified 6661 patients (19% women) who underwent intact AAA repair (87% EVAR; 83% women vs 88% men; P P P P P P P P = .02), but women less frequently underwent lower extremity revascularization (3.1% vs 8.2%; P = .03). Thirty-day mortality was higher in women after EVAR (3.2% vs 1.2%; P P = .04). After adjusting for repair type, age, aneurysm diameter, and comorbidities, female sex was independently associated with mortality (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.6; P = .02) and major complications (OR, 1.4; CI, 1.1-1.7; P P = .06) and major complications (OR, 1.1; CI, 0.9-1.4; P = .24) was reduced. Conclusions Women were at higher risk for 30-day death and major complications after intact AAA repair. Some of this disparity may be explained by differences in aortic size index, which should be further evaluated to determine the ideal threshold for repair.
Volunteer tourism in Romania as/for global citizenship

ABSTRACTThis paper examines short-term, volunteer tourism in Romania as a form of education for global citizenship. Drawing upon data collected through participant observation and qualitative interviews with numerous stakeholders, we argue that global citizenship education in this programme not only aligns with neoliberal governmentality, as others have deftly pointed out vis-a-vis volunteer tourism more broadly, but also has troubling implications for volunteering as civic engagement. Due to a short length of stay, a significant language barrier, limited professional or technical expertise, and a lack of knowledge of the service context, what volunteer tourists were able to do in a Romanian intentional community research context, was extremely limited: they primarily played with children. And while this childcare function occasionally offered pragmatic assistance to local community members, volunteers’ evolving understandings of the purposes and role of volunteering in global citizenship contrasted sharp...
Efficient Implicit Mode Matching Method for Complicated Periodic Waveguiding Structures

Mode matching (MM) is a popular method to analyze the multijunction dielectric waveguides. Conventionally, MM is subject to the high complexity of computation of adequate eigenmodes for matching the transverse fields at waveguide junctions. This letter introduces an implicit mode matching (IMM) method to efficiently analyze complicated periodic waveguiding structures with reduced computational and storage complexities. IMM adapts the spectral bi-Lanczos decomposition to avoid the expensive procedure of calculating eigenmodes explicitly. In this IMM, the optimized nonuniform step of bi-Lanczos iterations is leveraged to further reduce the computational complexity in simulating complicated periodic structures. Numerical results validate the feasibility of the proposed method. Moreover, the comparison with rigorous coupled wave analysis is performed to illustrate the application prospect of the proposed method.
Interconnect patterns for printed organic thermoelectric devices with large fill factors

Organic materials can be printed into thermoelectric (TE) devices for low temperature energy harvesting applications. The output voltage of printed devices is often limited by (i) small temperature differences across the active materials attributed to small leg lengths and (ii) the lower Seebeck coefficient of organic materials compared to their inorganic counterparts. To increase the voltage, a large number of p- and n-type leg pairs is required for organic TEs; this, however, results in an increased interconnect resistance, which then limits the device output power. In this work, we discuss practical concepts to address this problem by positioning TE legs in a hexagonal closed-packed layout. This helps achieve higher fill factors (∼91%) than conventional inorganic devices (∼25%), which ultimately results in higher voltages and power densities due to lower interconnect resistances. In addition, wiring the legs following a Hilbert spacing-filling pattern allows for facile load matching to each application...
Molecular treatment of charge transfer in Li + +Ca collisions

The perturbed-stationary-state method, appended with electron translation factors, has been applied to charge transfer in ${\mathrm{Li}}^{+}$ +Ca collisions for energies from 0.1 to 20 keV/amu. The Born-Oppenheimer wave functions and eigenvalues were generated using the pseudopotential technique, which reduced the many-electron system to a simpler two-electron problem. The molecular ground-state $X^{1}\ensuremath{\Sigma}^{+}$ is calculated to be bound and has the potential-well parameters ${R}_{e}=6.20{a}_{0}$, ${D}_{e}=1.11$ eV, ${\ensuremath{\omega}}_{e}=235$ ${\mathrm{cm}}^{\ensuremath{-}1}$, and ${B}_{e}=0.263$ ${\mathrm{cm}}^{\ensuremath{-}1}$. From the scattering computations, a representative value for the charge-transfer cross section is 4\ifmmode\times\else\texttimes\fi{}${10}^{\ensuremath{-}15}$ ${\mathrm{cm}}^{2}$ at 5 keV/amu. The cross section decreases rapidly as the energy is reduced below 1 keV/amu. At all energies studied, the dominant electron-capture reaction product is the ground-state Li atom.
The Hyposomatomedinemic Short Child

Until 1978, the usual way of identifying growth-hormone-deficient (GHD) children in the short population was to measure the serum level of immuno-reactive growth hormone (GH) during provocative tests, after exercising or during sleep. An alternative approach became possible in 1978 with the introduction of the radioimmunoassay (RIA) for somatomedin C (SMC).(1) When this assay was applied on a large scale to the population of short children, it became apparent that there were substantially more short children with low SMC levels than there were GHD children.(2) Furthermore, some of the hyposomatomedinemic boys and girls who had normal levels of immunoreactive GH responded with accelerated linear growth to long-term human growth hormone (hGH) treatment.(3–5) It was suggested, therefore, that some of these responsive, non-GHD short children might have a structurally abnormal form of endogenous GH.(3–6)
Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation

The synthesis and conformational analysis of a series of phenyl 2,3,6-tri-O-benzyl-β-d-thio galacto- and glucopyranosides and their 6S-deuterio isotopomers, with systematic variation of the protecting group at the 4-position, are described. For the galactopyranosides, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable shift in side chain population away from the trans,gauche conformation and in favor of the gauche,trans conformer. In the glucopyranoside series on the other hand, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable increase in the population of the trans,gauche conformer at the expense of the gauche,gauche conformer. The possible modulating effect of these conformational changes on the well-known changes in the anomeric reactivity of glycosyl donors as a function of protecting group is discussed, raising the possibility that larger changes may be observed at the transition state for glycosylat...
An Evaluation of Staff Preference for Graphic Characteristics

The purpose of the current study was to assess staff preference for how data were displayed on graphs. Specifically, preference for line versus bar graphs was assessed, as well as preference for da...
Community structural differences shape microbial responses to high molecular weight organic matter

The extent to which differences in microbial community structure result in variations in organic matter (OM) degradation is not well understood. Here, we tested the hypothesis that distinct marine microbial communities from North Atlantic surface and bottom waters would exhibit varying compositional succession and functional shifts in response to the same pool of complex high molecular weight (HMW-OM). We also hypothesized that microbial communities would produce a broader spectrum of enzymes upon exposure to HMW-OM, indicating a greater potential to degrade these compounds than reflected by initial enzymatic activities. Our results show that community succession in amended mesocosms was congruent with cell growth, increased bacterial production and most notably, with substantial shifts in enzymatic activities. In all amended mesocosms, closely related taxa that were initially rare became dominant at time frames during which a broader spectrum of active enzymes were detected compared to initial timepoints, indicating a similar response among different communities. However, succession on the whole-community level, and the rates, spectra and progression of enzymatic activities, reveal robust differences among distinct communities from discrete water masses. These results underscore the crucial role of rare bacterial taxa in ocean carbon cycling and the importance of bacterial community structure for HMW-OM degradation.
The role of ants in vertebrate carrion decomposition

Abstract We review the relevant literature on ant-carrion interactions, highlight what is known about ants in decomposition ecology, and present a framework for future studies that aim to quantify the direct and indirect effects of ants on decomposition. One hundred and fifty-four species of ants were documented on carrion. Ants were associated with carrion in a wide range of habitats on almost every continent. Ants directly affected decomposition by feeding on carcasses (necrophagy) and by lacerating carcasses. Ants indirectly affected decomposition by predating carrion-feeding invertebrates and by altering the microhabitat of carrion via nest and mound construction. Ants may profoundly impact forensic science primarily by altering the colonization or utilization of carrion by other carrion feeders. Despite the near ubiquity of ants on carrion, their role in decomposition ecology is vastly understudied. Future studies need to experimentally assess the direct and indirect effects of ants on decomposition and comparative studies of different ant species in varying environmental conditions would be particularly fruitful.
Risk of Skin Cancers with Long-Term Itraconazole in Lung Transplant Recipients

Purpose The objective of this study was to determine if long term itraconazole use, as antifungal prophylaxis, in lung transplant recipients is an independent risk factor for skin cancer. Methods We retrospectively reviewed patients who received a lung transplant at Mayo Clinic Rochester from 2002 to 2010. The antifungal prophylaxis protocol at our institution is triazole therapy, itraconazole or voriconazole, for a minimum of 3 years. Patients who died within 6 months of initial transplant were excluded. Characteristics to help assess independent risk for the development of cutaneous cancers and type of antifungal prophylaxis were noted. Patients who were exposed to both voriconazole and more than 6 months of itraconazole were analyzed separately. Results We identified 102 patients who underwent lung transplant at Mayo Clinic from 2002 to 2010; 11 patients died within 6 months of transplant and were excluded. Of the remaining 91 patients, 44 received only itraconazole prophylaxis, 10 received only voriconazole prophylaxis, and 37 received both itraconazole and voriconazole. No statistically significant difference between the baseline characteristics of the 3 groups was observed with the exception of race. There was a lower proportion of Caucasians in the voriconazole only group compared with the itraconazole only and combined itraconazole/voriconazole groups (p=0.02). Out of the 91 patients included in the study, 40 (44.0%) were diagnosed with skin cancer post-transplant, and 5 (12.5%) developed aggressive, metastatic cutaneous squamous cell carcinoma. Follow-up time was similar between patients who developed skin cancer (93.0 ± 45.0 months) and those who did not (62.0 ± 49.0 months, p=0.23). No significant difference was found in incidence of skin cancer or rate of metastatic squamous cell carcinoma between patients in the three groups (p=0.65) Duration of itraconazole was greater in patients who developed skin cancer [median 62.5 months (22.7, 87.5) vs 32.0 (18.0, 64.8), p=0.07] despite similar follow-up time. Absolute exposure (i.e. exposed to itraconazole or not) did not appear to correlate with the development of skin cancer post-transplant. Conclusion Prolonged itraconazole exposure when used as a prophylactic agent in lung transplant recipients appears to correlate with the development of skin cancers but further studies are warranted.
Euler Singularities from the Lagrangian Viewpoint

In the analysis of singular Euler flows, real or imagined, Lagrangian variables offer an attractive option, although it is well known that in many flow problems Lagrangian methods can be intractable. In other examples, Lagrangian variables are found to simplify the representation. We examine here some aspects of Lagrangian analysis of fluid flows, then focus on simple singular solutions of Euler’s equations having infinite kinetic energy. We use these solutions to explore the different forms taken by these flows in Eulerian and Lagrangian formulations. We then apply a Lagrangian construction to a set of singular flows in two dimensions, as examples of a general method. Finally, we comment on the analogous but far more difficult application of the method to singular Euler flows in three dimensions.
Witch-Hunts and Crime Panics in America

The term witch-hunt has been tossed around by media commentators, policy experts, and even presidents for years — Nixon, Clinton, and Trump each in turn. Accusations of a witch-hunt are used to signal perceived bias, procedural unfairness, and paranoia. This Article argues that drawing simplistic connections between witchcraft trials and unfairness in the criminal justice system severely hampers our understanding of both historical and contemporary events. It obscures the fact that the term witch-hunt is popularly used to describe two very different types of prosecutions that reflect distinct social and legal problems and demand distinct solutions. On the one hand, witch-hunts target individuals based on their beliefs and are exemplified by the two Red Scares of the early and mid-twentieth century and the persecution of the Quakers in seventeenth century Massachusetts Bay. These are fundamentally distinct from crime panics, which target activity that was already classified as criminal but do so in a way that reveals deep procedural deficiencies in the criminal justice system. Crime panics are exemplified by the Salem witchcraft trials and the “Satanic Panic” of the 1980s and 1990s. In contrast, the ongoing special investigation by Robert Mueller is neither a witch-hunt nor a crime panic. By bringing ongoing criminal law issues into conversation with legal history scholarship on early American witch-hunts, this article clarifies our understanding of the relationship between politics and large-scale criminal investigations, and highlights areas for future reform.
Dry Milk Solids Act

This act, commonly called the Dry Milk Solids Act, was passed “To fix a reasonable definition and standard of identity of certain dry milk solids.” It was amended only once to change the terminology from “nonfat dry milk solids or defatted milk solids” to “nonfat dry milk.” The act was not enacted as part of the Federal Food, Drug, and Cosmetic Act but was made applicable to it.
Development of a Monomeric Inhibitory RNA Aptamer Specific for FGFR3 that Acts as an Activator When Dimerized.

There have been limited options for people who suffer from fibroblast growth factor receptor (FGFR) signaling disorders. In this study, we developed RNA aptamers specific for FGFR3 as potential therapeutic agents. Using a structured aptamer library, we performed ten rounds of SELEX (systematic evolution of ligands by exponential enrichment) against mouse FGFR3c protein. Using an engineered BaF3 cell line, one aptamer clone from round 6 of the selection inhibited FGF-dependent cell growth with a concentration at which 50% of growth is observed (IC50) of ∼260 nM and bound both mouse and human FGFR3 but not FGFR1 or FGFR2. This inhibitor of FGFR3 signaling (iR3), when dimerized using a template-driven approach, resulted in a functional activator of FGFR3 (aR3). We validated the activity and specificity of iR3 and aR3 on engineered BaF3 cell lines, mouse and human FGFR protein, and primary cultures of neuroepithelial precursor cells.
The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein.

The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein is a multifunctional RNA binding protein implicated in a wide range of biological functions. Mechanisms and putative hnRNP A1-RNA interactions have been inferred primarily from the crystal structure of its UP1 domain bound to ssDNA. RNA stem loops represent an important class of known hnRNP A1 targets, yet little is known about the structural basis of hnRNP A1-RNA recognition. Here, we report the first high-resolution structure (1.92A) of UP1 bound to a 5'-AGU-3' trinucleotide that resembles sequence elements of several native hnRNP A1-RNA stem loop targets. UP1 interacts specifically with the AG dinucleotide sequence via a "nucleobase pocket" formed by the β-sheet surface of RRM1 and the inter-RRM linker; RRM2 does not contact the RNA. The inter-RRM linker forms the lid of the nucleobase pocket and we show using structure-guided mutagenesis that the conserved salt-bridge interactions (R75:D155 and R88:D157) on the α-helical side of the RNA binding surface stabilize the linker in a geometry poised to bind RNA. We further investigated the structural basis of UP1 binding HIViSL3(ESS3) by determining a structural model of the complex scored by small-angle X-ray scattering. UP1 docks on the apical loop of SL3(ESS3) using its RRM1 domain and inter-RRM linker only. The biophysical implications of the structural model were tested by measuring kinetic binding parameters, where mutations introduced within the apical loop reduce binding affinities by slowing down the rate of complex formation. Collectively, the data presented here provide the first insights into hnRNP A1-RNA interactions.
Application of volumetric absorptive microsampling (VAMS) to measure multidimensional anti-influenza IgG antibodies by the mPlex-Flu assay.

Introduction: Recently, volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 µL) on a volumetric swab, and long-term sample storage. The mPlex-Flu assay is a novel, high-throughput assay that simultaneously measures the concentration of antibodies against the hemagglutinin (HA) proteins from multiple influenza virus strains with ≤5 µL of serum. Here we describe combining these two methods to measure multidimensional anti-influenza IgG activity in whole blood samples collected by a finger stick and VAMS, with correction for serum volume based on simultaneous hemoglobin measurement. Methods: We compared capillary blood samples obtained from a finger stick using a VAMS device with serum samples collected by traditional phlebotomy from 20 subjects, with the influenza antibody profiles measured by the mPlex-Flu assay. Results: We found that results with the two sampling methods were highly correlated within subjects and across all influenza strains (mean R2 = 0.9470). Adjustment for serum volume, based on hemaglobin measurement, was used to estimate serum volume of samples and improved the accuracy. IgG measurements were stable over 3 weeks when VAMS samples were stored at room temperature or transported using a variety of shipping methods. Additionally, when volunteers performed finger-stick VAMS at-home by themselves, the comparison results of anti-HA antibody concentrations were highly consistent with sampling performed by study personnel on-site (R2 = 0.9496). Conclusions: This novel approach can provide a simple, accurate, and low-cost means for monitoring the IgG anti-influenza HA antibody responses in large population studies and clinical trials.
Factors Leading to Success for Entrepreneurs in the Chinese Online C2C Market

The purpose of the present study was to gain a deeper understanding of the Chinese online C2C market by exploring the roles of personal motivations, resources, and Chinese institutional environment (e.g., norms, culture) factors in business operations and success from the seller’s perspectives. In particular, the present study investigated online entrepreneurs’ means of identifying and acquiring different resources,the operational strategies they employed, and other factors they perceived to impact their business success. The findings of this study suggest that these entrepreneurs may benefit from positioning themselves in a carefully identified product category or apply novel operational strategies based on their possessed resources to achieve success. Specifically, proactive cultivation and leveraging of their external “guanxi” and implementation of technology may significantly enhance the effectiveness and efficiency of such efforts.
Federated Learning with Autotuned Communication-Efficient Secure Aggregation

Federated Learning enables mobile devices to collaboratively learn a shared inference model while keeping all the training data on a user’s device, decoupling the ability to do machine learning from the need to store the data in the cloud. Existing work on federated learning with limited communication demonstrates how random rotation can enable users’ model updates to be quantized much more efficiently, reducing the communication cost between users and the server. Meanwhile, secure aggregation enables the server to learn an aggregate of at least a threshold number of device’s model contributions without observing any individual device’s contribution in unaggregated form. In this paper, we highlight some of the challenges of setting the parameters for secure aggregation to achieve communication efficiency, especially in the context of the aggressively quantized inputs enabled by random rotation. We then develop a recipe for auto-tuning communication-efficient secure aggregation, based on specific properties of random rotation and secure aggregation – namely, the predictable distribution of vector entries post-rotation and the modular wrapping inherent in secure aggregation. We present both theoretical results and initial experiments.
Liquid biopsy of the immune environment: Evaluation of peripheral blood mononuclear cells (PBMCs) with CyTOF and response to trastuzumab (T)-based neoadjuvant chemotherapy (NAC) in HER2+ breast cancer (BC).

592Background: Immune responses in the tumor microenvironment have prognostic and predictive value in BC. However, the potential of immune responses observed in peripheral blood as biomarkers in BC...
Zanubrutinib (BGB-3111), a Second-Generation Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase and Its Utility in Treating Chronic Lymphocytic Leukemia

The understanding of the B cell receptor (BCR) pathway and its contribution to chronic lymphocytic leukemia (CLL) pathogenesis have led to the development of targeted BCR inhibitors which have transformed the treatment paradigm of CLL. Ibrutinib is a first-in-class oral Bruton's tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naive and relapsed/refractory setting as compared to traditional chemoimmunotherapy. Despite its clinical efficacy, many patients discontinue treatment due to adverse events, which are thought to be mediated through off-target kinase inhibition. Zanubrutinib is a second-generation non-covalent BTK inhibitor with higher potency, allowing for inhibition of BTK with fewer off target effects. Early phase clinical trials have demonstrated excellent efficacy and a well-tolerated safety profile. Long-term follow-up is needed, but zanubrutinib holds promise to be an effective therapy for CLL with a manageable side effect profile and will be an exciting addition to our treatment paradigm.
Systemic Lupus Erythematosus

Systemic lupus erythematosus typically manifests with fatigue, rash and joint pain in young women. However, this autoimmune disorder can affect any organ system and can cause severe disease leading to renal failure, stroke and death. Because systemic lupus erythematosus can present with many different organ system manifestations the clinician should consider connective tissue disease in the differential diagnosis.
Timing of diffusion weighted imaging lesions in spontaneous intracerebral hemorrhage

Abstract Introduction Diffusion weighted imaging (DWI) lesions are common after spontaneous intracerebral hemorrhage (sICH). However, their timing relative to a patient's admission to the hospital is unknown. The purpose of this study is to estimate the timing of new DWI lesions after admission for acute sICH. Material and methods Select patients enrolled in a single center prospective study examining the prevalence DWI lesions in acute primary sICH received two MRI scans of the brain after admission. The presence of a new DWI lesion between MRI scans was defined as a new DWI event. A lognormal parametric model was used to estimate the median time (50% percentile) to develop a new DWI lesion. Results Among the 121 participants enrolled in the study, 63 (52%) had two brain MRIs. The median time from admission to 1st MRI was 1 day (IQR 1.2, range 0.1–8.4). The median time between the 2 MRI scans was 2.1 (IQR 2.9, range 0.02–17.4) days. 30.2% (n = 19) of participants developed a new DWI lesion between MRI scans. The estimated median time from 1st MRI to new DWI event was 6.3 days (95% CI, 4.1 to 9.6). Discussion and conclusion Accounting for time from admission to 1st MRI, we found that 50% of new DWI lesions occurred by 7.3 days after sICH admission. Pathophysiologic changes in sICH during this time frame need to be studied in order to elucidate a mechanism for DWI lesions.
Continuing Medical Education Questions: October 2021.

Article Title: A comprehensive literature review and expert consensus statement on therapeutic drug 2 monitoring of biologics in inflammatory bowel disease.
The National Council for Community and Education Partnerships Presentation

This slide presentation reviews the importance of Science, Technology, Engineering and Math (STEM) education for the future of the country and for NASA.
A Computational Study of Axial Compressor Rotor Casing Treatments and Stator Land Seals

A COMPUTATIONAL STUDY OF AXIAL COMPRESSOR ROTOR CASING TREATMENTS AND STATOR LAND SEALS By Charles C. Cates, M.S.M.E. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Mechanical Engineering at Virginia Commonwealth University. Virginia Commonwealth University, 2006 Major Director: James T. McLeskey, Jr., Ph.D. Department of Mechanical Engineering As fuel prices soar ever higher, aircraft manufacturers and their airline customers demand that the next generation of engines used on their aircraft push the limits of efficiency and capability. This study consists of a computational examination of two currently accepted methods of axial compressor performance improvement in terms of surge margin and efficiency, rotor casing treatments and stator land seals. ADPAC and Fluent CFD solvers were used in the analysis of circumferential groove casing treatments and two types of stator seals, one typical of a fiont stage stator and one typical of a rear stage stator. The computational solutions and visualizations allowed for greater understanding of the complex flows inherent in each of these features. It was found that rotor tip vortex control plays a large part in the surge margin gains from a circumferential groove casing treatment. The efficiency gains of knife seals were dependent primarily on the gap size of the seals.
Cosmos 1129: spaceflight and bone changes.

Male Wistar rats were placed in orbit for an 18.5 day period aboard the Soviet Cosmos 1129 biological satellite. The skeletal changes which occurred during spaceflight were determined to be a reduced rate of periosteal bone formation in the tibial and humeral diaphyses, and a decreased trabecular bone volume and an increased fat content of the bone marrow in the proximal tibial metaphysis.
Nanomanufacturing-related programs at NSF

The National Science Foundation is meeting the challenge of transitioning lab-scale nanoscience and technology to commercial-scale through several nanomanufacturing-related research programs. The goal of the core Nanomanufacturing (NM) and the inter-disciplinary Scalable Nanomanufacturing (SNM) programs is to meet the barriers to manufacturability at the nano-scale by developing the fundamental principles for the manufacture of nanomaterials, nanostructures, nanodevices, and engineered nanosystems. These programs address issues such as scalability, reliability, quality, performance, yield, metrics, and cost, among others. The NM and SNM programs seek nano-scale manufacturing ideas that are transformative, that will be widely applicable and that will have far-reaching technological and societal impacts. It is envisioned that the results from these basic research programs will provide the knowledge base for larger programs such as the manufacturing Nanotechnology Science and Engineering Centers (NSECs) and the Nanosystems Engineering Research Centers (NERCs). Besides brief descriptions of these different programs, this paper will include discussions on novel
Ninety-five percent duodenectomy: an experimental study

Subtotal excision of the duodenum with perservation of the pancreas and bile and pancreatic ducts was achieved in five dogs without complications. Reconstruction was performed by direct anastomosis of the jejunum to the duodenal strip remaining attached to the head of the pancreas. Radiologic, metabolic, and histologic parameters 4 months postoperatively documented the success of this procedure. We suggest that this technique may be used to further investigate the role of the duodenum in digestive physiologic functions and may have clinical applications for benign diseases of the duodenum.
Preslip and cascade processes initiating laboratory stick slip

Recent modeling studies have explored whether earthquakes begin with a large aseismic nucleation process or initiate dynamically from the rapid growth of a smaller instability in a “cascade-up” process. To explore such a case in the laboratory, we study the initiation of dynamic rupture (stick slip) of a smooth saw-cut fault in a 76 mm diameter cylindrical granite laboratory sample at 40–120 MPa confining pressure. We use a high dynamic range recording system to directly compare the seismic waves radiated during the stick-slip event to those radiated from tiny (M −6) discrete seismic events, commonly known as acoustic emissions (AEs), that occur in the seconds prior to each large stick slip. The seismic moments, focal mechanisms, locations, and timing of the AEs all contribute to our understanding of their mechanics and provide us with information about the stick-slip nucleation process. In a sequence of 10 stick slips, the first few microseconds of the signals recorded from stick-slip instabilities are nearly indistinguishable from those of premonitory AEs. In this sense, it appears that each stick slip begins as an AE event that rapidly (~20 µs) grows about 2 orders of magnitude in linear dimension and ruptures the entire 150 mm length of the simulated fault. We also measure accelerating fault slip in the final seconds before stick slip. We estimate that this slip is at least 98% aseismic and that it both weakens the fault and produces AEs that will eventually cascade-up to initiate the larger dynamic rupture.
A type system for data-centric synchronization

Data-centric synchronization groups fields of objects into atomic sets to indicate theymust be updated atomically. Each atomic set has associated units of work, code fragments that preserve the consistency of that atomic set.We present a type system for data-centric synchronization that enables separate compilation and supports atomic sets that span multiple objects, thus allowing recursive data structures to be updated atomically. The type system supports full encapsulation for more efficient code generation. We evaluate our proposal using AJ, which extends the Java programming language with data-centric synchronization. We report on the implementation of a compiler and on refactoring classes from standard libraries and a multi-threaded benchmark to use atomic sets. Our results suggest that data-centric synchronization enjoys low annotation overhead while preventing high-level data races.
Applying a Formula for Generator Redispatch to Damp Interarea Oscillations Using Synchrophasors

If an interarea oscillatory mode has insufficient damping, generator redispatch can be used to improve its damping. We explain and apply a new analytic formula for the modal sensitivity to rank the best pairs of generators to redispatch. The formula requires some dynamic power system data and we show how to obtain that data from synchrophasor measurements. The application of the formula to damp interarea modes is explained and illustrated with interarea modes of the New England 10-generator power system.