cssi/SciSciGPT-SciSciNet huggingface dataset:
Cell signalling through thromboxane A2 receptors.

Abstract Thromboxane A 2 receptors (TPs) are widely distributed among different organ systems and have been localized on both cell membranes and intracellular structures. Following the initial cloning of this receptor class from human placenta, the deduced amino acid sequence predicted seven-transmembrane spanning regions, four extracellular domains and four intracellular domains, making TP a member of the seven-transmembrane G-protein-coupled receptor (GPCR) super family. A single gene on chromosome 19p13.3 leads to the expression of two separate TP isoforms: TPα which is broadly expressed in numerous tissues, and a splice variant termed TPβ which may have a more limited tissue distribution. Mutagenesis, photoaffinity labelling, and immunological studies have indicated that the ligand binding domains for this receptor may reside in both the transmembrane (TM) and extracellular regions of the receptor protein. In addition, separate studies have provided evidence that this receptor can couple to at least four separate G protein families. As a consequence, TP signalling has been shown to result in a broad range of cellular responses including phosphoinositide metabolism, calcium redistribution, cytoskeletal arrangement, integrin activation, kinase activation, and the subsequent nuclear signalling events involved in DNA synthesis, cell proliferation, cell survival and cell death. While activation of these different signalling cascades can all derive from TP stimulation, the relative signalling preference for a given cascade appears to be both tissue and cell specific. Finally, separate studies have indicated that TP signalling capacity can be both down-regulated by protein kinase activation and up-regulated by GPCR cross-signalling. Thus, the multitude of signalling events which derive from TP activation can themselves be modulated by endogenous cellular messengers.
On the Use of a Calibration Emitter for Source Localization in the Presence of Sensor Position Uncertainty

Sensor position uncertainty is known to degrade significantly the source localization accuracy. This paper investigates the use of a single calibration emitter, whose position is known to the sensor array, to reduce the loss in localization accuracy due to sensor position errors that are random. Using a Gaussian noise model, we first derive the Cramer-Rao lower bound (CRLB) for a time difference of arrival (TDOA)-based source location estimate with the use of a calibration source. The differential calibration technique that is commonly used in Global Positioning System through the use of a calibration source to mitigate the inaccuracy in satellite ephemeris data is analyzed. The analysis indicates that differential calibration in most cases cannot reach the CRLB accuracy. The paper then proceeds to propose an algebraic closed-form solution for the source location estimate using both TDOA measurements from the unknown and the calibration source. The proposed algorithm is shown analytically, under high signal-to-noise ratio (SNR) and small sensor position noise, or under moderate level of SNR and sensor position noise together with distant unknown and calibration sources, to reach the CRLB accuracy. Simulations are used to corroborate and support the theoretical development.
Laid to Order: Male Escorts Advertising on the Internet

This exploratory study was conducted to gain information on an emerging form of prostitution—online prostitution. Additionally, this study focused on male prostitution, as it is the type less likely to gain attention in prostitution research. This study used 83 websites that advertise male escorts to explore the type of information provided to potential customers. The results indicate that these male escorts provide a variety of information (e.g., prices, services). In addition, some differences were found between sites depending on the potential customer (e.g., male, female). The importance of sex research and implications for future research also are discussed.
Construction of a Chickpea Linkage Map and Its Comparison With Maps of Pea and Lentil

Journal of Heredity 199738:115-119; 0022-1503/97/J5.00 An integrated genetic linkage map of chickpea (Clcei) has been developed that consists of 9 morphological, 27 isozyme, 10 RFLP, and 45 RAPD markers covering 550 cM. The map was made from segregation data from populations of three interspecific crosses of cultivated chickpea (C. arietlnum, 2n = 16) and a closely related wild species (C. retlculatum, 2n = 16). The linkage map has 10 linkage groups representing the eight chromosomes of chickpea. Interspecific crosses were chosen for mapping because of the extremely low level of polymorphism found within the cultivated chickpea species. Several regions of the genome were found to be slightly skewed from the expected Mendellan ratios of alleles. The map was compared with published maps for pea (Plsum) and lentil (Lens). Five regions of the chickpea map have gene orders that are similar to those found in the pea genome. The degree of similarity is somewhat less than that found between pea and lentil, which is consistent with the evolutionary distances between these three genera. We have also observed that lentil genomlc DNA RFLP probes hybridize poorly to chickpea DNA, Indicating considerable divergence of these genomes at the sequence level.
Bayesian approach for flexible modeling of semicompeting risks data

Semicompeting risks data arise when two types of events, non-terminal and terminal, are observed. When the terminal event occurs first, it censors the non-terminal event, but not vice versa. To account for possible dependent censoring of the non-terminal event by the terminal event and to improve prediction of the terminal event using the non-terminal event information, it is crucial to model their association properly. Motivated by a breast cancer clinical trial data analysis, we extend the well-known illness-death models to allow flexible random effects to capture heterogeneous association structures in the data. Our extension also represents a generalization of the popular shared frailty models that usually assume that the non-terminal event does not affect the hazards of the terminal event beyond a frailty term. We propose a unified Bayesian modeling approach that can utilize existing software packages for both model fitting and individual-specific event prediction. The approach is demonstrated via both simulation studies and a breast cancer data set analysis.
A decade of theory of mind research on cayo santiago: Insights into rhesus macaque social cognition

Over the past several decades, researchers have become increasingly interested in understanding how primates understand the behavior of others. One open question concerns whether nonhuman primates think about others' behavior in psychological terms, that is, whether they have a theory of mind. Over the last ten years, experiments conducted on the free-ranging rhesus monkeys (Macaca mulatta) living on Cayo Santiago have provided important insights into this question. In this review, we highlight what we think are some of the most exciting results of this body of work. Specifically we describe experiments suggesting that rhesus monkeys may understand some psychological states, such as what others see, hear, and know, but that they fail to demonstrate an understanding of others' beliefs. Thus, while some aspects of theory of mind may be shared between humans and other primates, others capacities are likely to be uniquely human. We also discuss some of the broader debates surrounding comparative theory of mind research, as well as what we think may be productive lines for future research with the rhesus macaques of Cayo Santiago.
Monte Carlo and quasi-Monte Carlo methods

Monte Carlo is one of the most versatile and widely used numerical methods. Its convergence rate, O(N−1/2), is independent of dimension, which shows Monte Carlo to be very robust but also slow. This article presents an introduction to Monte Carlo methods for integration problems, including convergence theory, sampling methods and variance reduction techniques. Accelerated convergence for Monte Carlo quadrature is attained using quasi-random (also called low-discrepancy) sequences, which are a deterministic alternative to random or pseudo-random sequences. The points in a quasi-random sequence are correlated to provide greater uniformity. The resulting quadrature method, called quasi-Monte Carlo, has a convergence rate of approximately O((logN)kN−1). For quasi-Monte Carlo, both theoretical error estimates and practical limitations are presented. Although the emphasis in this article is on integration, Monte Carlo simulation of rarefied gas dynamics is also discussed. In the limit of small mean free path (that is, the fluid dynamic limit), Monte Carlo loses its effectiveness because the collisional distance is much less than the fluid dynamic length scale. Computational examples are presented throughout the text to illustrate the theory. A number of open problems are described.
Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4.

Myeloid-derived suppressor cells (MDSC) are potent inhibitors of anti-tumor immunity that facilitate tumor progression by blocking the activation of CD4+ and CD8+ T cells and by promoting a type 2 immune response through their production of IL-10 and down-regulation of macrophage production of IL-12. MDSC accumulate in many cancer patients and are a significant impediment to active cancer immunotherapies. Chronic inflammation has been shown recently to enhance the accumulation of MDSC and to increase their suppression of T cells. These findings led us to hypothesize that inflammation contributes to tumor progression through the induction of MDSC, which create a favorable environment for tumor growth. As chronic inflammation also drives type 2 immune responses, which favor tumor growth, we asked if inflammation mediates this effect through MDSC. We find that IL-1β-induced inflammation increased IL-10 production by MDSC and induces MDSC, which are more effective at down-regulating macrophage production of IL-12 as compared with MDSC isolated from less-inflammatory tumor microenvironments, thereby skewing tumor immunity toward a type 2 response. Inflammation heightens MDSC phenotype by signaling through the TLR4 pathway and involves up-regulation of CD14. Although this pathway is well-recognized in other myeloid cells, it has not been implicated previously in MDSC function. These studies demonstrate that MDSC are an intermediary through which inflammation promotes type 2 immune responses, and they identify the TLR4 pathway in MDSC as a potential target for down-regulating immune suppression and promoting anti-tumor immunity.
Identification of polymorphisms explaining a linkage signal: application to the GAW14 simulated data

We applied three approaches for the identification of polymorphisms explaining the linkage evidence to the Genetic Analysis Workshop 14 simulated data: 1) the genotype-IBD sharing test (GIST); 2) an approach suggested by Horikawa and colleagues; and 3) the homozygote sharing test (HST). These tests were compared with a family-based association test. Two linked regions with highest nonparametric linkage scores were selected to apply these methods. In the first region, Horikawa's method identified the most SNPs within the region containing the disease susceptibility locus, while HST performed best in the second region. However, Horikawa's method also had the most type I errors. These methods show potential as additional tools to complement family-based association tests for the identification of disease susceptibility variants.
In vivo organization of the FtsZ-ring by ZapA and ZapB revealed by quantitative super-resolution microscopy.

Summary In most bacterial cells, cell division is dependent on the polymerization of the FtsZ protein to form a ring- like structure (Z-ring) at the midcell. Despite its essential role, the molecular architecture of the Z-ring remains elusive. In this work we examine the roles of two FtsZ-associated proteins, ZapA and ZapB, in the assembly dynamics and structure of the Z-ring in Escherichia coli cells. In cells deleted of zapA or zapB, we observed abnormal septa and highly dynamic FtsZ structures. While details of these FtsZ structures are difficult to discern under conventional fluorescence microscopy, single-molecule-based super-resolution imaging method Photoactivated Localization Micros- copy (PALM) reveals that these FtsZ structures arise from disordered arrangements of FtsZ clusters. Quan- titative analysis finds these clusters are larger and comprise more molecules than a single FtsZ protofila- ment, and likely represent a distinct polymeric species that is inherent to the assembly pathway of the Z-ring. Furthermore, we find these clusters are not due to the loss of ZapB-MatP interaction in ΔzapA and ΔzapB cells. Our results suggest that the main function of ZapA and ZapB in vivo may not be to promote the association of individual protofilaments but to align FtsZ clusters that consist of multiple FtsZ protofilaments.
Competition: The Next Generation of Environmental Regulation?

A few months ago, Professor Wendy Wagner published an article in the Indiana Law Journal that advocated a “competition-based”approach to regulate toxic chemicals and other substances. In her proposed system, a company could obtain a certification from EPA that a product that it produces is environmentally superior to a competitor’s product, based on an adjudication between the companies. This would create an advantage for the company in the market, as the product could be labeled as superior to its competitor. Under Professor Wagner’s proposal, in light of the information disclosed in the adjudication, EPA could also ban the inferior product or impose other limits on it, in addition to certifying the superior product. While Professor Wagner’s proposal centers on toxic chemicals, she suggests that “competition-based” regulation could be applied on a broader scale. The attached article examines the advantages of Professor Wagner’s proposal and the challenges inherent in implementing it, and explores whether the proposal could be modified to minimize those challenges. Professor Wagner’s “competition-based” regulation proposal is a combination of command and control regulation and market-based alternatives, and could combine the strengths of both approaches. However, Professor Wagner’s proposal may be very difficult to implement because it requires EPA to make a decision to certify a product as “superior” based on a vague, largely undefined standard. For all of the reasons that EPA has had difficulty setting “harm-based” standards under other regulatory programs, it is likely to have difficulty making the determination of whether one product is “superior” to another with regard to its environmental and health impacts. In addition, the proposal provides EPA with broad discretion to resolve difficult policy decisions regarding “superiority” with limited public input and allows the agency to hide those policy decisions from public view. Further, Professor Wagner proposes that the agency make the “superiority” decisions through the formal rulemaking process, a process which has long been out of favor with agencies and Congress because it is expensive and time consuming. Formal rulemaking is also a poor vehicle for resolving the difficult questions of fact and policy that will be central to a determination that one product is environmentally superior to another. Finally, the cumbersome rulemaking process, combined with the vague standard for “superiority”, raises “environmental justice” concerns.
Hobbes, law, and public conscience

This paper brings forth the importance of public conscience in Hobbes’s account of politics and law. It connects this idea to the famous Martens Clause that played and continues to play a crucial role in international legal debates. The Martens Clause, part of the preliminary materials of the Hague Conventions, posits that humanity’s ‘public conscience’ should play a role in international legal norms concerning warfare when treaties or conventions do not provide guidance. The paper argues that Hobbes also appeals to public conscience in his construction of the relationship between law and politics. Rather than the private conscience that might challenge the sovereign, the public conscience is that which reflects moral principles such as equity which the paper argues is more important than justice in interpreting the law. The paper thus elucidates an important component of Hobbes’s theory and makes clear its relevance for international affairs.
Investigation of Structural Heterogeneity at the SPE Site Using Combined P‐Wave Travel Times and Rg Phase Velocities

We present analyses of the 2D seismic structure beneath Source Physics Experiments (SPE) geophone lines that extended radially at 100 m spacing from 100 to 2000 m from the source borehole. With seismic sources at only one end of the geophone lines, standard refraction profiling methods cannot resolve seismic velocity structures unambiguously. In previous work, we demonstrated overall agreement between body‐wave refraction modeling and Rg dispersion curves for the least complex of the five lines. A more detailed inspection supports a 2D reinterpretation of the structure. We obtained Rg phase velocity measurements in both the time and frequency domains, then used iterative adjustment of the initial 1D body‐wave model to predict Rg dispersion curves to fit the observed values. Our method applied to the most topographically severe of the geophone lines is supplemented with a 2D ray‐tracing approach, whose application to P ‐wave arrivals supports the Rg analysis. In addition, midline sources will allow us to refine our characterization in future work.
Beta-Gamma Directional Correlation in the Decay of Co 60 and Na 22

The differential and integral beta-gamma directional correlations in the decay of ${\mathrm{Co}}^{60}$ and ${\mathrm{Na}}^{22}$ have been measured with scintillation counters. Both beta transitions are allowed but have high $\mathrm{ft}$ values. Therefore, small anisotropies are not excluded. In the case of ${\mathrm{Co}}^{60}$ the anisotropy was found to be zero for all beta energies above 0.06 Mev; the integral anisotropy was measured to be $A=\ensuremath{-}0.0003\ifmmode\pm\else\textpm\fi{}0.0017$ (standard deviation). In the case of ${\mathrm{Na}}^{22}$ the results seem to indicate an energy dependence of the anisotropy; the value is uncertain because of coincidences between positrons and annihilation quanta.
Achy Breaky Heart: Palliative and Hospice Care in Advanced cardiac Disease (P13)

different mindset than traditional wound care yet is based on the same fundamental scientific principles. This workshop presents an approach to palliation in wound care that involves being able to properly assess a wound and determine if palliation is appropriate, developing a comprehensive strategy for palliation of various types of wounds, and managing symptoms of chronic wounds, especially pain and odor. The many benefits of an effective palliative wound program, including improved quality of life and achieving the goal of healing the whole person, will be addressed. The emphasis will be on palliative wound care helping to achieve hospice goals for the patient.
Marketing, Information, and Parental Choice: A Comparative Case Study of Third-Party, Federally Funded Out-of-School-Time Services

Information and promotional marketing play central but complex roles in market-based educational programs. This in-depth qualitative study examines these complexities using the case of Supplemental Educational Services, a parental choice program providing federally funded tutoring to low-income students in K–12 public schools. Examining the creation, dissemination, and use of information and promotional marketing is necessary in order to understand how aspects of market theory play out in reality. This kind of inquiry is especially important given that the theory of consumer action behind market-based programs is that parents1Throughout this paper, “parent” refers to parents and guardians. We use the term parent for simplicity, but the concept of parental choice, as well as the sample of participants in our study, includes nonparent guardians as well. will make the best decisions for their children's education, if they have sufficient information on which to base those decisions. Our data and analysis sug...
Subluxated cataract lens surgery using sutured segments or rings and implantation of toric intraocular lenses

Purpose To evaluate the intraoperative performance and postoperative outcomes of toric intraocular lens (IOL) with suture ring implantation in adult patients with subluxated lenses. Setting Department of Ophthalmology, Kaiser Permanente, Santa Clara, California, and the Eye Institute of Utah, Salt Lake City, Utah, USA. Design Retrospective case review. Methods Eyes with subluxated cataractous lenses and preoperative corneal astigmatism having toric IOL implantation with a sutured ring or segment were studied. Preoperative and postoperative analyses included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and cylindrical power postoperatively and 3, 6, and 12 months postoperatively. Results Twenty-one eyes of 15 patients were studied. The median follow-up was 14.6 months. The mean CDVA at the final follow-up (0.10 logMAR ± 0.15 [SD]) was significantly improved from the mean preoperative CDVA (0.73 ± 0.40 logMAR). Postoperative cylindrical power was significantly improved in all patients (mean reduction in astigmatism 2.37 ± 1.46 diopters). Patients who required postoperative enhancement had anterior laser capsulotomy for bilateral capsule phimosis (2 eyes), photorefractive keratectomy (1 eye), pupilloplasty (1 eye), and posterior laser capsulotomy (2 eyes). Conclusion Cataract removal and implantation of a toric IOL combined with a sutured ring or segment capsule stabilizing device was a safe and efficacious long-term solution for patients with subluxated cataract lenses and corneal astigmatism. Financial Disclosure Dr. Cionni has a financial interest in the modified capsular tension ring. Neither of the other authors has a financial or proprietary interest in any material or method mentioned.
Glass Formation in Systems Based on AgX (X=Cl, Br or I)

Glass formation in halide systems based on AgX (X=Cl, Br or I) has been investigated. Glasses were obtained for two- to four-component-systems containing 45-60mol% of AgX and other components such as KX, CsX, BaX2 and PbX2. The glass transition temperatures of AgCl-based and AgBr-based glasses were close to room temperature, while those of AgI-based glasses were about 50°C. Infrared absorption spectra of an AgI-based glass showed that the glass is rather moisture sensitive and that the cut-off wavelength is expected to be longer than 30μm. Characteristics of the glass-forming systems based on AgX and other monovalent metal halides which have been already reported, i.e., LiX and CuX, have been discussed also.
Regulators of Iron Absorption in the Small Intestine

The absorption of iron can not be explained solely by transferrin and iron. Therefore, a search was undertaken to discover other iron binding proteins in homogenates of rat duodenum. Using heat, ammonium sulfate precipitation, serial chromatography and immunologic methods, we have identified four iron binding substances which are both biologically and immunologically distinct from ferritin and transferrin. Two of these iron binding complexes are water soluble with molecular sizes of about 520,000 and 60,000 daltons respectively. One of the water insoluble proteins is soluble in triton X-100 and is probably a membrane protein with a molecular size of about 60,000 daltons. Insoluble mucin is believed to be the fourth newly identified iron binding complex.
Enhanced lithium niobate pyroelectric ionizer for chip-scale ion mobility-based gas sensing

We present a miniaturized lithium niobate (LiNbO 3 ) pyroelectric ionizer with enhanced ionization using copper electrodes attached to the LiNbO 3 crystal poled surfaces. The modified device shows a ∼2.4x improvement in ionization count, without any increase in the heating power applied to the crystal. The ionization events had peak and average ionization currents of 44.8 nA and 9.36 pA respectively. The ionizer includes an integrated temperature sensor for precise control of the thermal cycling of the crystal. The ion generation is done at atmospheric pressure, with low voltages, paving the way for the ionizer integration in a chip-scale compatible portable platform.
MINK1: The missing link between ROS and its inhibition of Th17 cells

In this issue of JEM, Fu et al. (https://doi.org/10.1084/jem.20161120) identified the kinase Mink1 as a novel negative regulator of Th17 cell generation. Mink1, activated by reactive oxygen species (ROS), prevents TGF-β activation of Smad2, therefore limiting Th17 cell differentiation.
Fluid-Structure Interaction Modeling in 3D Cerebral Arteries and Aneurysms

In recent years, there have been great interests in fluid-structure interaction (FSI) problems due to their relevance in biomedical applications. However, several difficulties have hindered the development of partitioned FSI algorithms in modeling cerebral arteries and aneurysms. For example, the relatively small values of the mass ratio between the arterial wall and the blood will cause instabilities in coupled solvers, the arterial wall responses are very complicated therefore difficult to be described by classical structural models, accurate simulations in patient-specific geometries require large CPU time, and so on. To resolve these difficulties, the investigation of proper models for the aneurysms and the design of efficient and stable numerical schemes of these models are considered in this chapter. To be specific, we first contribute on stabilizing the partitioned fluid-structure interaction procedure and resolving the added-mass effect, then develop and employ fractional PDEs to model the complex biomechanical viscoelastic properties of patient-specific aneurysms. To validate the optimal coefficient analysis, the FSI framework is applied to patient-specific aneurysms, hence demonstrating the general applicability of the proposed model and the developed methodology.
Social Justice Pedagogy: Simple Gestures of Humanity

Social justice is a distinct national agenda in teacher education reform. In the report of the AERA Panel on Research and Teacher Education, panel members Cochran-Smith and Fries (2005) conceptualize social justice educators to “be professional educators as well as activists who commit to diminishing the inequities of American Society” (p. 45). We agree with Cochran-Smith and Fries that the work of teacher education professors needs to be informed by this agenda; thus, this conceptualization is important to our commitment as social justice educators. We understand the what, the why, and the how political agendas and established institutional norms intersect pedagogical ethics for social justice, resulting in a systematic silencing or ignoring the challenges of rectifying social and educational inequities. We perceive the what in the policies and mandates embedded in the No Child Left Behind (NCLB) legislation because they demonstrate formulaic approaches to the achievement of academic progress. At the state level, an emphasis on prescriptive approaches leading to “fast track” teacher “licensure” requirements is another demonstration of the intersection between institutionalized political agendas and social justice pedagogy. In the face of these realities, social justice educators teach “against the grain” in order to provide equitable and accessible education for ALL students.
The effect of leukocyte elastase on tissue factor pathway inhibitor

Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type inhibitor that directly inhibits factor Xa and, in a factor Xa- dependent fashion, also inhibits the factor VIIa/tissue factor (TF) catalytic complex. The Kunitz-2 domain in TFPI is needed for the binding and inhibition of factor Xa, while the Kunitz-1 domain appears to be responsible for binding factor VIIa in a quaternary factor Xa- TFPI-factor VIIa/TF inhibitory complex. Human leukocyte elastase (HLE) proteolytically cleaves TFPI between threonine-87 and threonine-88 within the polypeptide that links the Kunitz-1 and Kunitz-2 domains in the TFPI molecule. HLE treatment not only affects the ability of TFPI to inhibit factor VIIa/TF, but also dramatically reduces its inhibition of factor Xa. Both purified HLE and stimulated neutrophils regenerate TF activity from a preformed factor Xa-TFPI-factor VIIa/TF inhibitory complex. Kinetic analysis suggests that HLE cleavage does not effect the affinity of the initial encounter interaction between factor Xa and TFPI, whereas it markedly reduces the affinity of the final factor Xa:TFPI complex with Ki (final) values for untreated and HLE-treated TFPI of 58 pmol/L and 4.4 nmol/L, respectively. Thus, an epitope in the amino-terminal region of TFPI or a conformation of the TFPI molecule that requires the presence of this region is needed in concert with the Kunitz-2 domain to produce optimal inhibition of factor Xa by TFPI.
The Tricyclic Antidepressants

Depression is a common, albeit probably underdiagnosed and undertreated, disorder of late adult life.1 This illness affects an estimated 7–11% of individuals over 65 years of age.2 When depression is properly diagnosed and treated, the prognosis for recovery is good, even in older patients. Pharmacotherapy remains the mainstay of treatment of affective illness in all age groups.
Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort

The successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan-Meier techniques. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval (P < 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 (P < 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; P < 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; P < 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a "real-life" MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. Cancer Immunol Res; 6(9); 1039-45. ©2018 AACR.
Definitions of Gender and Sex: The Subtleties of Meaning

Definitions of the word “gender” were collected from 137 participants, who also completed questionnaires designed to determine aspects of the usage of the words “gender” and “sex.” The majority of participants were European American (86.9%), followed by Latino/a (3.6%), Asian/Asian American (2.9%), African American (2.2%), Native American (1.5%), and West Indian (1.5%). Most participants (70.9%) had attended at least some college and occupations included students (43%), professionals (27.8%), health care workers (4.3%), technical workers (5%), sales and service workers (9.4%), maintenance workers (1.4%), and business owners (1.4%). Data were examined to see which common themes emerged from the free form “define gender” question, the amount of interchangeability of “sex” and “gender” in a sentence completion task, and the varieties of beliefs about the relation between the terms “gender” and “sex.” Results indicate a variety of understandings and beliefs about gender that range from the common response that “gender” is the same as ”sex” to some less common responses that associate gender with females or discrimination. Implications of the ambiguous meaning of “gender” are discussed with an emphasis on the responsibility of researchers to clarify their own understanding of the terms when they discuss gender or sex in their research and publications.
Capitalist origins of the English Revolution

At a recent American Sociological Association meeting, a prominent sociologist defended the sweep of the the neo-Marxist theory by stating: “Damn the facts. A good theory is hard to find.” I agree; a good theory is hard to find. But when the facts are this damning, perhaps it is time to look harder for another.
Morphologic Diversity of Martian Ripples: Implications for Large-Ripple Formation

Large ripples with meter‐scale wavelengths are ubiquitous across Mars. Curiosity's traverse of the Bagnold Dune Field revealed a morphologic diversity of large Martian ripples that helps constrain their formative mechanism. Large ripples develop in isolated fields and on dunes. They form transversely and obliquely to longitudinally to the net sand‐flux direction in unimodally and bimodally distributed very fine to very coarse sand. They have either straight or sinuous crestlines. Inactive ripples are covered with dust, whereas migrating ripples are dust free. Here we present a unifying view of ripples that form in near‐bed sediment‐transport conditions (encompassing fluid‐drag and coarse‐grained ripples) to explain the range of large‐Martian‐ripple morphologies and expand the use of bedforms as environmental indicators.
Complete Resection Is Essential in the Surgical Treatment of Gestational Trophoblastic Neoplasia.

Objective The aim of this study was to determine the utility of surgery in patients with gestational trophoblastic neoplasia (GTN). Materials and Methods We performed a retrospective institutional review board–approved analysis of all patients with GTN at a single institution from 1985 to 2015 and compared all patients who underwent surgery as definitive management for their disease to a matched cohort of those who did not. Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). Results Sixty-nine patients underwent a total of 94 surgeries as definitive treatment for GTN. Nineteen patients had multiple surgeries. Progression-free survival and OS were improved in patients with complete macroscopic surgical resection (n = 61) compared with patients with gross residual disease (n = 33) (median PFS 91.2 months vs 3.3 months, and median OS not reached at 108.8 months vs 66.3 months, respectively; P Conclusions Complete resection results in improved outcomes in patients who undergo surgery for GTN, whether emergent or planned, independent of disease site, and should be considered as an important component of treatment in some situations.
Hyperspectral data analysis of the world's leading agricultural crops (Conference Presentation)

This presentation summarizes the advances made in the last 50 years in understanding, modeling, and mapping terrestrial vegetation as reported in the new book on “Hyperspectral Remote Sensing of Vegetation” (Publisher:Taylor and Francis inc.) and well as some very recent research. The advent of spaceborne hyperspectral sensors or imaging spectroscopy (e.g., NASA’s Hyperion, ESA’s PROBA, and upcoming Italy’s ASI’s Prisma, Germany’s DLR’s EnMAP, Japanese HIUSI, NASA’s HyspIRI) as well as the advances made in processing when handling large volumes of hyperspectral data have generated tremendous interest in advancing the hyperspectral applications’ knowledge base to large areas. Advances made in using hyperspectral data, relative to broadband data, include: (a) significantly improved characterization and modeling of a wide array of biophysical and biochemical properties of vegetation, (b) ability to discriminate plant species and vegetation types with high degree of accuracy, (c) reducing uncertainties in determining net primary productivity or carbon assessments from terrestrial vegetation, (d) improved crop productivity and water productivity models, (e) ability to assess stress resulting from causes such as management practices, pests and disease, water deficit or water excess, and (f) establishing more sensitive wavebands and indices to study vegetation characteristics. The presentation will discuss topics such as: (1) hyperspectral sensors and their characteristics, (2) methods of overcoming the Hughes phenomenon, (3) characterizing biophysical and biochemical properties, (4) advances made in using hyperspectral data in modeling evapotranspiration or actual water use by plants, (5) study of phenology, light use efficiency, and gross primary productivity, (5) improved accuracies in species identification and land cover classifications, and (6) applications in precision farming.
TILOS local scale Technology Innovation enabling low carbon energy transition

Abstract Community renewable energy and citizens' energy needs are crucial issues on the global political agenda. The indispensable legislative and regulatory, while also the necessary technological, societal and behavioral developments in order to support the energy transition will require public understanding and ownership to deliver their full potential. The main discussion is how to enable low-carbon energy transitions based on renewable-energy technologies such as wind turbines, solar panels, biogas plants or geothermal plants. Digitalization of energy and distributed storage are shaping the future of electricity use. Micro Grids (MG) on the other hand represent the means by which the purpose will be achieved. In Tilos island Technology Innovation for the Local Scale Optimum Integration of Battery Energy Storage (TILOS) case, it has been identified that the Quadruple Helix's (QH) components are accelerating the transfer of research and innovation results to regional growth while stressing the replicating potentials. Taking into consideration all parameters involved, while learning from pioneers' evidence, low-carbon energy transition and energy supply for isolated areas can be achieved. Finally the energy ecosystem space metamorphosis creates the new emerging structures and norms.
Supersymmetry constraints on U-duality invariant deformations of $N \geq 5$ Supergravity

Candidate counterterms break E7 type U-duality symmetry of $N \geq 5$ supergravity theories in four dimensions \cite{Kallosh:2011dp}. A proposal was made in \cite{Bossard:2011ij} to restore it, starting with a double set of vector fields and argued that a supersymmetric extension of their proposal should exist. We show that the extra vectors, needed for the deformation, can not be auxiliary fields in an eventual off-shell formulation $N \geq 5$ supergravity, assuming that such a formulation exists. Furthermore we show that these extra vector fields can not be dynamical either since that changes the unitary supermultiplets underlying these theories and requires one to go beyond the standard framework of extended simple supergravities. To show this we list all relevant unitary conformal supermultiplets of $SU(2,2|N+n)$. We find that doubling of vectors consistent with linearized supersymmetry requires to change the number of scalars, violating the coset structure of the theory, and also to add a finite number of higher spin fields, which do not admit consistent couplings to theories with spins $\leq 2$. Thus, the proposed duality restoring deformation along the lines of \cite{Bossard:2011ij} can not be implemented within the standard framework of extended supergravity theories. We argue therefore that, in the absence of anomalies, E7 type duality together with supersymmetry, might protect $N \geq 5$ supergravity from UV divergences, in particular, $N=5$ supergravity at 4 loops in d=4.
Regulatory oversight and trade-offs in earnings management: evidence from pension accounting

I develop approaches that quantify the use of discretion for the three main assumptions used for the financial reporting of defined benefit pension obligations: the expected return, the discount rate, and the compensation rate. I then apply these approaches to two regulatory events that affected a different subset of these three assumptions. Across both settings, my analyses indicate that firms reduced discretion in response to regulatory scrutiny—but only in those assumptions targeted by the regulatory event. In contrast, I find that firms increased the use of discretion in the other assumptions, consistent with a substitution effect. I also find that the use of discretion in the discount rate and compensation rate are approximately two to three times more effective at changing reported earnings than the use of discretion in the expected return. Collectively, my analyses highlight the interdependence of the three main pension assumptions and the relative weakness of the expected return as an earnings management tool.
A historical examination of police firearms

This study provides a historical examination of firearms in policing to understand how weapons have evolved within the American field. A search was conducted of historical newspaper databases and a...
“Why Try? Comparing the Aims of Parties and Amici in U.S. Supreme Court Litigation”

Why do litigants and amici curiae appeal to the U.S. Supreme Court? The judicial politics literature tells us that litigants do so primarily to win the case while amici are more concerned with the ...
Characterization of glycan determinants that mediate recognition of the major Wuchereria bancrofti circulating antigen by diagnostic antibodies

The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this "AD12 epitope". It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but such antigens are not detected in the sera of individuals with most other filarial infections. We report here functional and biochemical analyses that shed light on the interaction between filarial glycoproteins and AD12 and/or Og4C3. Binding of these monoclonal antibodies to a mammalian glycan array suggests the reactive moiety has structural similarity to terminal β-d-glucuronic acid in a 1-3 linkage to other hexoses. However, sera collected from individuals with patent W. bancrofti infection had very low or undetectable serum antibodies to the GlcA-containing array glycans. Unlike other filarial glycoproteins, the Wb-CFA is relatively resistant to protease digestion by pronase and trypsin and completely resistant to the mucinase O-sialoglycoprotein endopeptidase (OSGE). The protease resistance of the Wb-CFA may contribute to its consistent detection in Wb-infected sera.
Radioactivity of Be 10

The formation of radioactive ${\mathrm{Be}}^{10}$ by the ($d,p$) reaction from beryllium has been observed. The assignment of the activity to beryllium is the result of very careful chemical separations. ${\mathrm{Be}}^{10}$ emits negative electrons with an upper limit of 560\ifmmode\pm\else\textpm\fi{}50 kev (end point in Al = 180\ifmmode\pm\else\textpm\fi{}20 mg/${\mathrm{cm}}^{2}$). The half-life is very long; data are given from which its value could be computed if the yield were known.
Targeting metastatic cancer.

Despite recent therapeutic advances in cancer treatment, metastasis remains the principal cause of cancer death. Recent work has uncovered the unique biology of metastasis-initiating cells that results in tumor growth in distant organs, evasion of immune surveillance and co-option of metastatic microenvironments. Here we review recent progress that is enabling therapeutic advances in treating both micro- and macrometastases. Such insights were gained from cancer sequencing, mechanistic studies and clinical trials, including of immunotherapy. These studies reveal both the origins and nature of metastases and identify new opportunities for developing more effective strategies to target metastatic relapse and improve patient outcomes. Increased understanding of the biology of metastases allows improved targeting and outcomes for patients with both micro- and macrometastases.
Fostering Production of Pharmaceutical Products in Developing Countries

Today, most of the pharmaceutical products consumed in developing countries are imported. For many years, some lawmakers, scholars, and activists have argued that firms located in each developing country should produce more of those products locally. This would benefit the residents of those countries both by creating high-paying skilled jobs and by addressing more quickly and reliably the residents’ changing health needs. Skeptics have responded that local production would be less efficient and would impair quality control. Three recent developments have strengthened substantially the case for augmenting local production of pharmaceutical products: the emergence of new infectious diseases that pose unprecedented threats to developing countries; the sudden surge in health-care nationalism, which has undermined the ability of developing countries to rely on imports of drugs and vaccines; and revelation of the prevalence in those countries of falsified and substandard drugs. After reviewing the tangled history of efforts to promote local production, this paper proposes five strategies that would help future initiatives of this sort succeed: (a) a nonobvious combination of substantive and procedural reforms that would ensure that local firms have legal authority to produce the drugs at issue; (b) using the regulatory and purchasing power of the governments of developing countries to catalyze collaborations between established pharmaceutical firms and local licensees; (c) accelerating technology transfer through an international apprenticeship system; (d) ensuring that local-production initiatives employ from the outset some new, robust quality-control technologies; and (e) capitalizing on the economic and political power of regional economic communities in Africa, Latin America, and Asia.