cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular Mechanism of Biased Ligand Conformational Changes in CC Chemokine Receptor 7

Biased ligand binding to G protein-coupled receptors enables functional selectivity of intracellular effectors to mediate cellular function. Despite the significant advances made in characterizing the conformational states (transmembrane helical arrangements) capable of discriminating between G protein and arrestin binding, the role of the ligand in stabilizing such conformations remains unclear. To address this issue, we simulate microsecond dynamics of CC chemokine receptor 7 (CCR7) bound to its native biased ligands, CCL19 and CCL21, and detect a series of molecular switches that are mediated by various ligand-induced allosteric events. These molecular switches involve three tyrosine residues (Y1123.32, Y2556.51, and Y2887.39), three phenylalanine residues (F1163.36, F2085.47, and F2486.44), and a polar interaction between Q2526.48 and R2947.45 in the transmembrane domain of CCR7. Conformational changes within these switches, particularly hydrogen bond formation between Y1123.32 and Y2556.51, lead to g...
Common electrocardiogram variations pre- and post-marathon.

Key Clinical Message Electrocardiographic changes can be present in marathon runners. These findings may be misinterpreted as malignant by healthcare providers. For example, incomplete right bundle branch block, early ventricular repolarization, and left ventricular hypertrophy by voltage criteria alone are quite common in athletes, yet considered benign.
Retrospective longitudinal observation of caries around restorations by quantitative light-induced fluorescence

Caries lesions that develop around restorations (CARS) are the main reason for restoration replacement. The aim of this study was to assess whether surfaces that developed CARS and progressed to cavitation have a different fluorescent profile than surfaces that have restorations and no associated lesions. Quantitative light-induced fluorescence (QLF) images of occlusal, buccal, or lingual surfaces of permanent molars from 569 consented children followed up for 48 months as part of a longitudinal study (Ferreira Zandona et al, 2010, 2013) with an amalgam restoration and no associated caries lesion at baseline as determined by visual examination using the International Caries Detection and Assessment System (ICDAS) were selected. Surfaces (n = 22) that progressed to cavitation (ICDAS ≥5) at follow-up and randomly selected surfaces (n = 22) with no change at follow-up were analyzed for QLF parameters: area (A [mm2]), fluorescence loss (∇F [%]), and ∇Q [% × mm2]. Single, calibrated, and masked examiner (CPP) analyzed the images. Means and slopes between progressed and nonprogressed surfaces were compared using linear mixed effects models. ∇F, ∇Q, and ∇A increased significantly (P ≤ 0.0001) at a faster rate for surfaces that developed CARS and progressed to cavitation compared to restorations with no associated lesions. Surfaces with amalgam restorations that developed associated caries and progressed to cavitation have a different fluorescent profile than surfaces that have amalgam restorations and no associated lesions. Within the limitations of this study, QLF could assess the development of CARS in vivo. Analyses of amalgam restorations with associated lesions that do not progress to cavitation are warranted.
Imaging Transcription Dynamics in Single Cancer Cells

Over 50% of cancer patients harbor a mutation in the tumor suppressor protein p53. In healthy cells during stress, p53 recognizes specific genomic response elements (REs) to induce expression of stress response genes involved in cell cycle arrest, apoptosis and DNA damage. To maintain genomic stability, expression of these tumor suppression genes must be rapidly turned on and off. It is currently poorly understood how p53 spatiotemporally regulates expression of target genes in the complex milleu of the nucleus and how this process goes awry in cancer cells.To better mechanistically decipher changes in stress response gene expression in cancer cells, we established a single molecule imaging system that allows us simultaneously to track p53 and RNA Polymerase II binding along with transcription dynamics in single live cells. Single particle tracking studies indicate a dynamic interaction between p53 and chromatin that varies in distinct sub-nuclear compartments. Live cell monitoring of gene expression from a p53 target gene reveals dynamic bursts of transcription in discrete sub-nuclear regions. Modulation of wild-type p53 levels leads to changes in the transcription burst frequency and intensity. Introduction of cancer associated mutant p53 into cells leads to changes in both p53 sub-nuclear localization and transcription bursting dynamics. Future studies will focus on how chromatin structure dynamically regulates sub-nuclear localization and expression of p53 targets genes. This work is supported in parts via the 4D Nucleome consortia NIH grant 1U01EB021236-01.
FLT3 Mutant Activation Is Still Dependent on FLT3 Ligand.

Abstract FLT3 is a member of the class III receptor tyrosine kinase family and is primarily expressed on hematopoietic stem/progenitor cells. FLT3 ligand (FL) interacts with wild-type FLT3 (wtFLT3) receptors leading to the activation of FLT3 signaling. Constitutive activation of wt FLT3 through autocrine activation by FL is also observed in a number of cell lines and primary AML samples. Incubation of leukemic blasts expressing FLT3 with FL results in enhanced proliferation and decreased spontaneous apoptosis in many cases of acute leukemia. Somatic mutations of FLT3 involving internal tandem duplication (ITD) of the juxtamembrane domain or point mutations in the tyrosine kinase domain (TKD) have been identified in approximately 17–34% and 7–9% of acute myeloid leukemia (AML) patients, respectively. The ITD and TKD mutations appear to activate the tyrosine kinase domain of FLT3 in a FL-independent manner. However, these data were all obtained in human and murine cell lines that express FL. Thus, it is not clear whether FL also plays a role in the activation of FLT3 mutants. In order to determine whether or not FLT3 mutants are completely or somewhat dependent on FL, a FL deficient murine embryo fibroblast cell line (MEF) was derived from FL deficient (FL−/−) mice by SV40 large T antigen transformation. This eliminates the possibility of autocrine stimulation of transfected FLT3 receptor by FL. Expression of FLT3/ITD and FLT3/TKD mutations in FL−/−MEF cells resulted in some constitutive phosphorylation of FLT3 receptor. However, a more than 4 fold increase of FLT3 activation was induced by addition of FL. Retroviral introduction of FL in FL−/− MEF cells expressing FLT3 mutants led to more than 3 fold and 2 fold increase of tyrosine phosphorylation of FLT3 and AKT, respectively. In addition, FL expression resulted in a 3 fold increase of phosphorylation of STAT5 in FL−/−MEF cells expressing FLT3/ITD. In these FL expressing cells, addition of exogenous FL showed no further stimulation of FLT3, AKT and STAT5. These data strongly suggest that the level of FLT3 activation mediated by FLT3 mutants is still largely dependent on FL.
Cooperative Pathways to Acute Myeloid Leukemia Include the Combining of Transcription Factor Alterations: PML-RARα Cooperates with SOX4.

One paradigm for transformation of normal myeloid cells into acute myeloid leukemia (AML) is the combining of transcription factor alteration with activation of signaling pathways, including cytokine receptor activation. To identify possible alternative pathways to leukemogenesis we crossed MRP8-PML/RARA transgenic mice with BXH-2 mice, which harbor an endogenous retrovirus that causes AML. Approximately half of the leukemias that arose in this cross showed features of acute promyelocytic leukemia (APL). We identified 22 insertions sites in 8 APL-like leukemias. Of these, 7 represented common insertion sites in the Mouse Retroviral Tagged Cancer Gene Database (RTCGD, http://rtcgd.ncifcrf.gov/mm4/index.html). We introduced into a retroviral vector cDNAs encoding 6 genes located at retroviral insertion sites identified in PML/RARA leukemias ( Sox4 , Meis1 , Lck , Sfpi1 , Nfil3 , Cblb ). PML/RARA transgenic bone marrow was transduced with these retroviruses and the marrow was used to reconstitute lethally irradiated recipient animals. Recipients of PML/RARα transgenic marrow transduced with a SOX4 retrovirus developed APL-like leukemias in 3 months. SOX4 is an HMG box transcription factor that exhibits sequence specific DNA binding and transactivation. It is the most common insertion site in RTCGD, and has been found to be overexpressed in small cell lung cancer and medulloblastoma, as well as other tumors. In light of other data indicating that combining transcription factor abnormalities can rapidly induce leukemia (e.g. Hoxa9 + Meis1), our finding that SOX4 + PML/RARα is potently leukemogenic supports the hypothesis that such cooperativity represents another important paradigm in myeloid leukemogenesis.
Geriatric Cardio-oncology

As cancer therapies improve and the population as a whole ages, the number of elderly patients with cancer rises. Aging cancer patients are particularly vulnerable to cardiotoxicity from cancer treatment. Cardiotoxicity results from several factors in older patients: age-related factors, direct cardiac injury related to certain chemotherapy drugs (anthracyclines, trastuzumab, tyrosine kinase inhibitors, platinums, etc.), and changes in functional status as a result of cancer or cancer treatments. Use of comprehensive geriatric assessments in the care of elderly patients receiving cancer therapy is recommended as a strategy to improve outcomes. Aggressive screening of risk factors, early detection of cardiovascular injury, and close collaboration between oncologists and cardiologists are critical for optimizing cardiovascular health and cancer outcomes in older patients.
Protection and temperature-dependent switching characterization of latest generation 10 kV SiC MOSFETs

Silicon Carbine (SiC) based power semiconductor devices have increased voltage blocking capability, in the meantime, satisfactory switching performance as compared to conventional Silicon (Si) devices. This paper focuses on the latest generation 10 kV / 20 A SiC MOSFETs and investigates their protection schemes and temperature-dependent switching characteristics. A high voltage double pulse test platform is constructed including solid state circuit breaker, gate drive and hot plate under device under test (DPT) for temperature-dependent characterization. A behavioral model is established to analytically investigate switching performance of 10 kV SiC MOSFETs, and the temperature-dependent factors are studied in detail. The experimental results under various load currents and gate resistances from 25 C to 125 C at 7 kV dc-link voltage are presented.
Synthesis and Structure of 3,3-Dimethylindoline Squaraine Rotaxanes.

Squaraine rotaxanes are mechanically interlocked molecules comprised of a dumbbell shaped squaraine dye inside a tetralactam macrocycle. Previous squaraine rotaxanes have employed planar squaraine dyes with 4-aminophenyl, 2-aminothiophene, or N-amino units appended to the central C4O2 core. Here we describe two rotaxanes that encapsulate a 3,3-dimethylindoline squaraine inside a tetralactam with anthracene sidewalls. The rotaxanes were prepared by a templated clipping reaction and an X-ray crystal structure shows that the squaraine gem-dimethyl groups force a relatively wide separation between the macrocycle anthracene sidewalls. The decreased interaction between the encapsulated squaraine and the anthracene sidewalls leads to a smaller red shift of the squaraine absorption and emission bands. Solution-state studies show that the gem-dimethyl groups in 3,3-dimethylindoline squaraine dyes are large enough to prevent macrocycle threading or rotaxane unthreading. One of the new rotaxanes emits an orange ligh...
Anatipopecten and the Rotularia Vernon/ Zone (Late Eocene) in Peninsular Florida

One of the best guide fossils found in the Late Eocene Rotularia vernoni Zone (Asterocyclina-Spirulaea vernoni Zone of Puri, 1957) in peninsular Florida is a species of Anatipopecten (Plate I). The ribs of this pectinid are so different from other pectens found in the Ocala Group that even a fragment can be easily recognized as Anatipopecten. This distinctive pectinid is common but not abundant in the Rotularia vernoni Zone of the Crystal River Formation; yet, it remains relatively poorly known.
Thermal Convection Loop Tests of Nb-1% Zr Alloy in Lithium at 1200 and 1300°C

This paper describes the effect of temperature on the mass transfer of niobium alloys in lithium as determined in thermal convection loop tests to 1300°C. All loops were operated for 3000 h in an u...
Twenty-First-Century Imperatives

The twenty-first century is an era of of disruptive innovation and ever-increasing complexity that is being fueled by hyper-connectivity and convergence among technologies and disciplines. According to the 2014 National Academy of Science (NAS) report on convergence, The key message of convergence, however, is that merging ideas, approaches, and technology from widely diverse fields of knowledge at a high level of integration is one crucial strategy for solving complex problems and addressing complex intellectual questions underlying emerging disciplines. This chapter discusses twenty-first century trends, the promise and challenges of hyperconnectivity and the Internet of Things, and the problems posed by ever-growing system complexity.
Economic Aspects of Groundwater Development and Use

Abstract The choice of an optimal structure for a groundwater extraction system depends upon a large number of variables which are site specific, including such things as labor and capital costs, soil and slope conditions of lands to be irrigated, and the relative scarcity of water. These considerations notwithstanding, useful insights into the cost structure of groundwater use can be obtained by examining such costs within the context of conditions in the Southwestern United States, with emphasis given to relative costs and the tradeoffs between components of the groundwater extraction system. This is the end sought in this paper. Major components of the groundwater extraction system which are examined in this paper include water distribution systems, pumps, and alternative fuel types. Fixed and variable costs are described for each system, and conditions under which alternative extraction systems might be preferable are discussed. The primary trade-offs considered in these discussions are those between labor and capital intensive systems, and those between alternative distribution systems.
Wrongs, Crimes, and Criminalization

I will focus on Tadros’s general views about criminalization and how he contends philosophers should not think about it. Misguided approaches, according to Tadros, include attempts to identify principles that constrain the scope of the criminal law, as well as efforts to establish that given considerations constitute reasons for or against the use of the penal sanction. In what follows, I begin with a few general remarks about the connections between Tadros’s treatment of criminal justice and the real world. Next, I try to salvage the viability of the two approaches to criminalization he rejects. Finally, I turn a skeptical eye to what I take to be the most radical thesis in Wrongs and Crimes: the state should occasionally criminalize conduct that is not wrongful.
A Strategic Approach to Target Capital Investment on Facility Assets: Literature Review

ABSTRACT Analysis of a strategic planning framework, proposed by Edward Zielinski, focused on reducing operational costs in Facility Management (FM) through using long-term best practices in capita...
NORMAL VIBRATIONS OF AROMATIC RINGS

Summary * A restudy of the vibrations of benzene and such related nitrogenous aromatics as symmetrical tri-azine, pyridine, and the di-azines and tetrazines has been carried out. The basic new assumption is the formulation of the potential energy in the Urey-Bradley form; this is found to describe these molecules satisfactorily, and to lead to revisions and improvements in the vibrational assignments including that of benzene.
BAG2: A process-portable framework for generator-based AMS circuit design

We present BAG2, a framework for the development of process-portable Analog and Mixed Signal (AMS) circuit generators. Such generators are parametrized design procedures that produce schematics, layouts, and verification testbenches for a circuit given input specifications. This paper expands on previous work by introducing a universal AMS circuit verification framework into BAG2, as well as two new layout engines, XBase and Laygo, that enable development of process-portable layout generators. We have developed various complex circuit generators as driving examples, including a time-interleaved SAR ADC and a SerDes transceiver frontend. Instances of these designs have been produced in a TSMC 16nm FFC process; we however verify our claims of process portability by presenting circuits generated (using a single methodology code-base and only primitives adapted to the specific process) in various technology nodes, including TSMC 28nm, TSMC 16nm, GLOBALFOUNDRIES 45nm RF-SOI, ST 28nm FD-SOI, and GLOBALFOUNDRIES 22nm FDX.
Rings of Continuous Functions from an Algebraic Point of View

When George Martinez invited me, close to a year ago to give a talk on rings of continuous functions at a conference on ordered algebraic systems in an exotic location, I felt honored and elated. The accompanying feeling of euphoria stayed with me until I started to think seriously about what I could say to an audience containing people thoroughly familiar with the Gillman-Jerison text [GJ1] and many of the ensuing developments since 1960 — a lot of them due to mathematicians to whom I would be talking. I began to wonder if I would be doing the equivalent of carrying coals to Curacao in August.
The tech writing game

Here's all the information the aspiring technical writer needs -- from how and where to train, to landing and holding a job, to perfecting one's skills and mastering the tools of the trade.
Automatic Domain Adaptation for Parsing

Current statistical parsers tend to perform well only on their training domain and nearby genres. While strong performance on a few related domains is sufficient for many situations, it is advantageous for parsers to be able to generalize to a wide variety of domains. When parsing document collections involving heterogeneous domains (e.g. the web), the optimal parsing model for each document is typically not obvious. We study this problem as a new task --- multiple source parser adaptation. Our system trains on corpora from many different domains. It learns not only statistics of those domains but quantitative measures of domain differences and how those differences affect parsing accuracy. Given a specific target text, the resulting system proposes linear combinations of parsing models trained on the source corpora. Tested across six domains, our system outperforms all non-oracle baselines including the best domain-independent parsing model. Thus, we are able to demonstrate the value of customizing parsing models to specific domains.
Effects of cinnamon extract on glycogen synthase kinase 3 phosphorylation of tau

Recently correlations have been suggested between abnormal glucose metabolism and the development of Alzheimer’s disease. These suggested links stem from the similar portions of the insulin signali...
Quantitative Susceptibility Mapping of Magnetic Quadrupole Moments

We modeled the magnetic field up to the quadrupole term to investigate not only the average susceptibility (dipole), but also the susceptibility distribution (quadrupole) contribution. Expanding the magnetic field up to the order provides the quadrupole ( : monopole, : dipole). Numerical simulations were performed to investigate the quadrupole contribution with subvoxel nonuniformity. Conventional dipole and our dipole + quadrupole models were compared in the simulation, the phantom and human brain. Furthermore, the quadrupole field was compared with the anisotropic susceptibility field in the dipole tensor model. In a nonuniformity case, numerical simulations showed a nonnegligible quadrupole field contribution. Our study showed a difference between the two methods in the susceptibility map at the edges; both the phantom and human studies showed sharper structural edges with the dipole + quadrupole model. Quadrupole moments showed contrast mainly at the structural boundaries. The quadrupole moment field contribution was smaller but nonnegligible compared to the anisotropic susceptibility contribution. Nonuniform and uniform source distributions can be separately considered by quadrupole expansion, which were mixed together in the dipole model. In the presence of nonuniformity, the susceptibility maps may be different between the two models. For a comprehensive field model, the quadrupole might need to be considered along with susceptibility anisotropy and microstructure effects.
Safety and Risk Assessment

A comprehensive and patient-centered safety and risk assessment for an older adult may not only provide immediately actionable clinical information but also insight into potential future risk and opportunities for prevention. Domains explored in this chapter include home safety, high-risk behaviors, and elder mistreatment—three topics that can profoundly affect medical and social outcomes. First, home safety assessments provide clinicians with a valuable window into the patient’s environment and functional status. Next, personal risk behaviors of substance use and sexual health are examined because older adults are not immune to the increasing misuse of prescription medications, to the dangers of alcohol and illicit substances, or to the rising rates of sexually transmitted infections. Lastly, elder mistreatment is reviewed, inclusive of physical and sexual abuse, emotional and psychological abuse, financial exploitation, and the frequently under-recognized phenomenon of elder neglect.
An Examination of Undergraduate Conductor Practice Behavior

The purpose of this study was to examine undergraduate conductors’ personal approaches to conducting practice, practice time allocation, and beliefs about their conducting abilities. Participants (...
The Politics of Translating Sound Motifs in African Fiction

Starting with the premise that aesthetic choices reveal the ideological stances of translators, the author of this research monograph examines works of fiction by postcolonial African authors writing in English or French, the genesis and reception of their works, and the translation of each one into French or English. Texts include those by Nuruddin Farah from Somalia, Abdourahman Ali Waberi from Djibouti, Jean-Marie Adiaffi from Cote d’Ivoire, Ayi Kwei Armah from Ghana, Chenjerai Hove from Zimbabwe, and Assia Djebar from Algeria, and their translations by Jacqueline Bardolph, Jeanne Garane, Brigitte Katiyo, Jean-Pierre Richard, Josette and Robert Mane, and Dorothy Blair. The author highlights the aural poetics of these works, explores the sound motifs underlying their literary power, and shows how each is articulated with the writer’s literary heritage. She then embarks on a close examination of each translator’s background, followed by a rich analysis of their treatments of sound. The translators’ strategies for addressing sound motifs are contextualized in the larger framework of postcolonial literatures and changing reading materialities.
Decentralized Multi-setting Adaptive Distribution Protection Scheme for Directional Overcurrent Relays

Widespread integration of distributed energy resources (DERs) in the power distribution system has left the conventional protection schemes ineffective in adequately identifying and isolating a fault. Hence, modern protection schemes should be able to adapt to these variations and modify the protective device's settings to ensure effective protection coordination. Although prior works have addressed this issue using extensive communication-based methods (centralized or peer-to-peer), the actual implementation of these methods is economically less viable shortly considering the present infrastructure. However, with the advent of modern digital relays, protection schemes can be made adaptive yet keeping them decentralized and hence, easily implementable and deployable. The work proposed in this paper aspires to achieve this goal by utilizing the commonly used protective devices such as directional overcurrent relays in the power distribution systems by storing versatile setting groups enabling better observability of the relays towards fault identification and isolation in the absence of extensive communication links.
Interactions between Oligoethylene Glycol-Capped AuNPs and Attached Peptides Control Peptide Structure.

Peptide-functionalized nanoparticles (NPs) often rely on a well-defined peptide structure to function. Here, we report the attachment of model peptides to the ligand shell of AuNPs passivated with oligoethylene glycol (OEG). Specifically, peptides containing the repeating (LLKK)n motif plus either one or two reactive functional groups were covalently linked to OEG-capped, ∼5 nm AuNPs via the Cu+-catalyzed azide-alkyne cycloaddition reaction. This work builds on a previous study from our group in which an (LLKK)n peptide having two reactive functional groups was considered. Peptide attachment was confirmed by FTIR spectroscopy. Amino acid analysis was used to determine that 3-4 peptides were immobilized per AuNP. Circular dichroism spectroscopy revealed a structural change from random coil in solution to α-helical upon attachment to OEG-capped AuNPs. The key result of this study is that the nature of the capping layer on the AuNP surface influences peptide structure to a significant degree. Other important findings resulting from this work are that the AuNP-peptide conjugates reported here are water soluble and that the long axis of the helical peptides is oriented tangent to the AuNP surface. The latter point is important for applications involving biorecognition.
Preliminary evidence that oxytocin does not improve mentalizing in women with schizophrenia.

Abstract Introduction Mentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. Methods We tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. Results In contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. Conclusion These findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.
Association of medicaid expansion of the Affordable Care Act with the stage at diagnosis and treatment of papillary thyroid cancer: A difference-in-differences analysis.

Abstract Background The Affordable Care Act’s (ACA) Medicaid expansion has increased insurance coverage and improved various cancer outcomes. Its impact in papillary thyroid cancer (PTC) remains unclear. Methods Non-elderly patients (40-64 years-old) with PTC living in low-income areas either in a 2014 expansion, or a non-expansion state were identified from the National Cancer Database between 2010 and 2016. Insurance coverage, stage at diagnosis, and RAI administration were analyzed using a difference-in-differences analysis. Results 10,644 patients were included. Compared with non-expansion states, the percentage of uninsured patients (adjusted-DD -2.6% [95%-CI -4.3to-0.8%],p = 0.004) and patients with private insurance decreased, and those with Medicaid coverage increased (adjusted-DD 9.7% [95%-CI 6.9–12.5%],p Conclusions Medicaid expansion has resulted in a smaller uninsured population in PTC patients, but without earlier disease presentation nor change in RAI treatment.
Discount Rate Uncertainty and Capital Investment

Firms obtain noisy estimates of investors' required rates of return (discount rates) using market-based information. Discounted-cash-flow (DCF) methods, as commonly taught in MBA courses, lead to upward-biased estimates of project values in the presence of such noise, even when cash flow and discount rate estimates are unbiased, due to Jensen's inequality. We show that this bias affects corporate investment decisions and firm financial performance, and we test additional predictions derived from the DCF model in the presence of noisy discount rates. Our evidence implies that a one-standard-deviation increase in discount rate uncertainty is associated with increased firm investment of 6.8%, while profitability decreases by 4.1%.
Disparities in NCCN Guideline Compliant Care for Resectable Cholangiocarcinoma at Minority-Serving Versus Non-Minority-Serving Hospitals

Racial/ethnic disparities in cancer outcomes may relate to variations in receipt of National Comprehensive Cancer Network (NCCN) guideline compliant care. Patients undergoing resection of cholangiocarcinoma (CCA) between 2004 and 2015 were identified using the National Cancer Database (NCDB). Institutions treating Black and Hispanic patients within the top decile were categorized as minority-serving hospitals (MSH). Factors associated with receipt of NCCN-compliant care, and the impact of NCCN compliance on overall survival (OS), were evaluated. Among 16,108 patients who underwent resection of CCA, the majority of patients were treated at non-MSH (n = 14,779, 91.8%), while a smaller subset underwent resection of CCA at MSH (n = 1329, 8.2%). Patients treated at MSH facilities tended to be younger (MSH: 65 years versus non-MSH: 67 years), Black or Hispanic (MSH: 59.9% versus non-MSH: 13.4%), and uninsured (MSH: 11.6% versus non-MSH: 2.2%). While overall compliance with NCCN care was 73.0% (n = 11,762), guideline-compliant care was less common at MSH (MSH: 68.8% versus non-MSH: 73.4%; p < 0.001). On multivariable analyses, the odds of receiving non-NCCN compliant care remained lower at MSH (OR 0.76, 95% CI 0.65–0.88). While white patients had similar odds of NCCN-compliant care with minority patients when treated at MSH (OR 0.98, 95% CI 0.75–1.28), minority patients had lower odds of receiving guideline-compliant care when treated at non-MSH (OR 0.85, 95% CI 0.75–0.96). Failure to comply with NCCN guidelines was associated with worse long-term outcomes (HR 1.60, 95% CI 1.52–1.69). Patients treated at MSH had decreased odds to receive NCCN-compliant care following resection of CCA. Failure to comply with guideline-based cancer care was associated with worse long-term outcomes.
The Naked Truth from the Single Stock Futures Market

In this paper, we use a novel high-frequency data set, provided by the OneChicago single stock futures exchange, to study the impact of short sale restrictions on asset prices. Contrary to Battalio and Scultz (2006), we find many violations to the put call parity relation and to the cost of carry model even when using perfectly synchronous futures and stock prices. Most of these violations occur in a direction consistent with stocks being short-sale constrained. Examining the future put call parity relation that involves no equity, we find that futures and options are fairly priced, relative to each other. Constructing an implied intra-day measure of stock's short-sale rebate rate from stock and futures prices, we show that, contrary to many critics' claims, the SEC's ban of naked short selling on 19 financial stocks in July 2008 was highly effective in raising the overall cost of shorting. After remaining at the zero level for a week, on the first day the ban was effective, the average implied short sale rebate rate on the 19 financial firms instantly dropped to -4% p.a. and eventually -8% p.a. within a couple of days.
Cost Utility of Lifelong Immunoglobulin Replacement Therapy vs Hematopoietic Stem Cell Transplant to Treat Agammaglobulinemia

Importance Lifelong immunoglobulin replacement therapy (IRT) is standard-of-care treatment for congenital agammaglobulinemia but accrues high annual costs ($30 000-$90 000 per year) and decrements to quality of life over patients' life spans. Hematopoietic stem cell transplant (HSCT) offers an alternative 1-time therapy, but has high morbidity and mortality. Objective To evaluate the cost utility of IRT vs matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT to treat patients with agammaglobulinemia in the US. Design, setting, and participants This economic evaluation used Markov analysis to model the base-case scenario of a patient aged 12 months with congenital agammaglobulinemia receiving lifelong IRT vs MSD or MUD HSCT. Costs, probabilities, and quality-of-life measures were derived from the literature. Microsimulations estimated premature deaths for each strategy in a virtual cohort. One-way sensitivity and probabilistic sensitivity analyses evaluated uncertainty around parameter estimates performed from a societal perspective over a 100-year time horizon. The threshold for cost-effective care was set at $100 000 per quality-adjusted life-year (QALY). This study was conducted from 2020 across a 100-year time horizon. Exposures Immunoglobulin replacement therapy vs MSD or MUD HSCT for treatment of congenital agammaglobulinemia. Main outcomes and measures The primary outcomes were incremental cost-effectiveness ratio (ICER) expressed in 2020 US dollars per QALY gained and premature deaths associated with each strategy. Results In this economic evaluation of patients with congenital agammaglobulinemia, lifelong IRT cost more than HSCT ($1 512 946 compared with $563 776 [MSD] and $637 036 [MUD]) and generated similar QALYs (20.61 vs 17.25 [MSD] and 17.18 [MUD]). Choosing IRT over MSD or MUD HSCT yielded ICERs of $282 166 per QALY gained over MSD and $255 633 per QALY gained over MUD HSCT, exceeding the US willingness-to-pay threshold of $100 000/QALY. However, IRT prevented at least 2488 premature deaths per 10 000 microsimulations compared with HSCT. When annual IRT price was reduced from $60 145 to below $29 469, IRT became the cost-effective strategy. Findings remained robust in sensitivity and probabilistic sensitivity analyses. Conclusions and relevance In the US, IRT is more expensive than HSCT for agammaglobulinemia treatment. The findings of this study suggest that IRT prevents more premature deaths but does not substantially increase quality of life relative to HSCT. Reducing US IRT cost by 51% to a value similar to IRT prices in countries implementing value-based pricing may render it the more cost-effective strategy.
Overcoming Radioresistance of Lung Cancer Stem Cells

Every year lung cancer claims more lives than any other cancer type. Poor outcomes in this disease are linked to the development of resistance to existing treatments, including radiotherapy. Radioresistance in lung cancer may be driven by a population of cancer cells with properties in common with normal stem cells, including limitless self-renewing potential. These “cancer stem cells” are capable of reconstituting tumors following treatment and of seeding metastatic sites. In this chapter, we review the evidence implicating cancer stem cells in the radioresistance of cancers of the lung and other tissues. Strategies for interfering with mechanisms of radioresistance within cancer stem cells are discussed. Therapeutic modifications that augment the effects of radiotherapy on CSCs are likely to improve outcomes for lung cancer patients.
A nutrient-sensing pathway regulates leptin gene expression in muscle and fat

Leptin, the protein encoded by the obese (ob) gene, is synthesized and released in response to increased energy storage in adipose tissue. However, it is still not known how incoming energy is sensed and transduced into increased expression of the ob gene. The hexosamine biosynthetic pathway is a cellular 'sensor' of energy availability and mediates the effects of glucose on the expression of several gene products. Here we provide evidence for rapid activation of ob gene expression in skeletal muscle by glucosamine. Increased tissue concentrations of the end product of the hexosamine biosynthetic pathway, UDP-N-acetylglucosamine (UDP-GlcNAc), result in rapid and marked increases in leptin messenger RNA and protein levels (although these levels were much lower than those in fat). Plasma leptin levels and leptin mRNA and protein levels in adipose tissue also increase. Most important, stimulation of leptin synthesis is reproduced by either hyperglycaemia or hyperlipidaemia, which also increase tissue levels of UDP-N-acetylglucosamine in conscious rodents. Finally, incubation of 3T3-L1 pre-adipocytes and L6 myocytes with glucosamine rapidly induces ob gene expression. Our findings are the first evidence of inducible leptin expression in skeletal muscle and unveil an important biochemical link between increased availability of nutrients and leptin expression.
Constrained Crystal Structure Refinement

In the previous chapters we have had a very general discussion of the mathematics of fitting a “model” to a set of data, but there has been very little discussion of the nature of the appropriate model, except for the implicit one that the first partial derivatives of the predicting function with respect to all parameters must exist. We shall now turn to the specific question of the determination of the parameters of a crystal structure by fitting diffraction data to a mathematical model of the structure.
A Review of “Sacred Strategies: Transforming Synagogues From Functional to Visionary”

As a scholar who mentors doctoral students doing congregational studies and as a religious educator, I was excited to find a new book that has studied Jewish congregations. As a religious educator ...
Optical communication over the turbulent atmospheric channel using spatial diversity

Optical communication through clear atmosphere provides a means for high data rate communication (Gbps) over relatively short distances (/spl sim/km). However, turbulence in the atmosphere leads to fades of varying depths, some of which may lead to heavy loss of data. We consider spatial diversity at both the transmitter and receiver as a means to mitigate the short-term loss of signal strength. Using direct detection receivers and binary pulse position modulation as an example, we derive the outage probability of spatial diversity systems that use equal gain combining and optimal combining. The power gain of using these spatial diversity systems is found to be substantial. Hence, we feel diversity systems should be used as the key technique for clear atmospheric optical channels.
CONSIDERACIONES DIAGNÓSTICAS Y TERAPÉUTICAS PARA INFECCIONES UTERINAS EN VACAS LECHERAS

From an animal health-well being, welfare, and performance perspective, the postpartum period is comprised of an early window where acute health and cow survival is an issue with the development of septic metritis. Subsequently, sustained presence of endometritis is likely to be contributing to sub-fertility in lactating dairy cows with an overall herd pregnancy rate of approximately 16%. The challenge is to integrate on commercial dairies preventive medicine programs with reproductive management to improve herd fertility. Cows affected by periparturient disorders such as hypocalcemia, dystocia, and retained fetal membranes are more likely to contract uterine infections than cows that calve normally are. Thus, appropriate management of the transition period is critical in the prevention of uterine infections at the herd level. In addition, a postpartum program to monitor health to provide treatment to cows in the early stages of disease should be implemented.
Quadratic FIR-filter design as a generalized eigenproblem

This work suggests optimizing quadratic performance measures on (possibly multi-rate) DSP systems in order to design one or more embedded FIR filters, which might be real or complex and with or without linear-phase, N-th band, or other structure. The outlined approach replaces the eigenproblem of the eigenfilter design method with a generalized eigenproblem. A general capability results for minimizing an arbitrary nonnegative-definite (purely) quadratic system-performance measure subject to a single arbitrary equality constraint on a second such quadratic. Using this one constraint to fix the impulse-response energy in nonembedded single-filter design results in the ordinary eigenfilter method. A simple example and a geometric interpretation show that alternate equality constraints can profoundly affect the solution. Finally a multirate matched-filtering-system example design impossible with the ordinary eigenfilter method hints at the flexibility of the approach.
Dissolved-air foam separation to clarify turbid waters

Abstract An experimental investigation is presented of the foam separation of turbidity constituents, primarily clays, from natural waters at approximately neutral pH. A cationic surfactant, cetyldimethylbenzylammonium chloride, is used as the collector-frother. A continuous flow clarification unit has been designed and utilized, relying on the precipitation of dissolved-air bubbles (with the air dissolved at 40–80 psig) from suspension to provide the interfacial area for particle attachment and flotation. Data from 91 experiments is correlated on the basis of an empirical model. The effluent turbidity (particle concentration in terms of optical density) and effluent surfactant concentration are related to the five independent variables by stepwise, linear multiple regression analysis. A second order model relates the effluent turbidity to the feed rate, feed turbidity, feed surfactant concentration, the recirculation rate, and the liquid column height, with an accuracy of 20 per cent. Scale-up considerations are included, and an operating-cost estimate is given for a 1000 gal day −1 clarification unit.
Influence of freshwater macrophytes on the littoral ecosystem structure and function of a young Colorado reservoir

Abstract The presence of rooted macrophytes, mostly the milfoil Myriophyllum sibiricum, was manipulated in enclosures in the littoral zone of a Colorado reservoir. The presence of macrophytes significantly increased the abundance of major invertebrate taxa by 70–1725% and increased the emission of methane 127%. The increase in abundance of most invertebrates was probably due to the habitat and surfaces provided by milfoil as stable isotope analyses indicated that milfoil was an insignificant carbon source for all of the invertebrate taxa, except for the milfoil midge Cricotopus myriophylli. Cricotopus is known to specialize on milfoil (other members of the genus specialize on Hydrilla or are generalists), had an isotopic signature that indicated a diet of milfoil, and was about 15 times more abundant when milfoil was present than when it was absent. Milfoil had no detectable effect on the total particulate phosphorus (TPP), soluble reactive phosphorus (SRP), total dissolved phosphorus (TDP), dissolved organic phosphorus (DOP), and Chl a of water within the enclosures. However, enclosures containing milfoil had higher concentrations of SRP in the pore water of surface sediments than enclosures that had milfoil removed. SRP in pore water dropped below 2 μg/L at >2 cm sediment depth and DOP increased progressively from nearly zero at the surface to about 150 μg/L at 15 cm depth, regardless of vegetation. Thus, milfoil had significant effects on many, but not all, measures of littoral ecosystem structure and function that were monitored.
Wages for Wives: Renegotiating Gender and Production Relations in Contract Farming in the Dominican Republic

Abstract This study analyzes the intersection of gender and production relations in small-scale contracting in nontraditional agriculture. The case of the processing tomato industry in the Dominican Republic exemplifies patterns found throughout the region. Building on a critique of unitary household models, I analyze the gendered relations mobilizing resources for contract farming. As appears common, contracting has heightened demand for women's farm labor. Contracting has simultaneously provided women with openings for contesting the appropriation of their unpaid labor and many women are claiming payment for work in contract farming. This case demonstrates the importance of gender issues in informing contract farming debates and policy interventions.
Epistemological beliefs across faculty experts and student non‐experts

The epistemological beliefs of non‐experts or novices have been studied with some frequency, while the beliefs of experts as a comparison group have received little attention in research literature. The purpose of the current study was to examine whether the conceptual framework of epistemological beliefs may be considered statistically similar or invariant across a sample of experts and non‐experts within a university context. To achieve the purpose of this study, multi‐group structural equation models were examined. Results suggest support for the five‐dimension structure of epistemological beliefs across both experts and non‐experts and indicate experts as having statistically significantly higher overall epistemological beliefs as measured within this university context.
Repetition blindness and bilingual memory: token individuation for translation equivalents.

The repetition blindness effect (RB) occurs when individuals are unable to recall a repeated word relative to a nonrepeated word in a sentence or string of words presented in a rapid serial visual presentation task. This effect was explored across languages (English and Spanish) in an attempt to provide evidence for RB at a conceptual level using noncognate translation equivalents (e.g., nephew-sobrino). In the first experiment, RB was found when a word was repeated in an English sentence but not when the two repetitions were in different languages. In the second experiment, RB was found for identical repetitions in Spanish and in English using word lists. However, the cross-language condition produced significant facilitation in recall, suggesting that although conceptual processing had taken place, semantic overlap was not sufficient to produce RB. The results confirm Kanwisher's (1987) token individuation hypothesis in the case of translation equivalents.