cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance

C219 Camptothecin (CPT) derivatives are effective anticancer drugs, especially against solid tumors. As camptothecins are chemically unstable and have clinical limitations, we have synthesized indenoisoquinolines as novel topoisomerase I (Top1) inhibitors. We presently report two indenoisoquinoline derivatives NSC 725776 and NSC 724998 that have been selected for therapeutic development. Both are potent Top1 inhibitors and induce Top1 cleavage at unique genomic positions compared to camptothecin. Consistent with Top1 poisoning, protein-linked DNA breaks were detected in cells treated with NSC 725776 and NSC 724998 at nanomolar concentrations. Those drug-induced protein-linked DNA breaks persisted longer after drug removal than those produced by CPT, topotecan or SN-38, the active metabolite of irinotecan. Studies in human cells in culture show that NSC 725776 and NSC 724998 exert antiproliferative activity at nanomolar concentrations. Furthermore, NSC 725776 and NSC 724998 demonstrate cross-resistance in cells deficient or silenced for Top1, which is consistent with their selective Top1 targeting. Whereas topotecan and SN-38 exhibit resistance in cells overexpressing ABCG2 (MXR/BCRP), NSC 724998 (and to a lesser extent NSC 725776) showed full activity in ABCG2-overexpressing cells, indicating that the new indenoisoquinolines can overcome resistance to camptothecins. Similar to other known Top1 inhibitors, NSC 725776 and NSC 724998 treated cells show an arrest of cell cycle progression in both S and G2/M and a dependence on functional p53 for their cytotoxicity. Dose dependent histone gamma-H2AX foci formation was readily observed in cells treated with NSC 725776 and NSC 724998. These gamma-H2AX foci were detectable at pharmacologically relevant doses for up to 24 hours and thus could be used as biomarkers for clinical trials (phase 0-I).
Revisiting Mediation in the Social and Behavioral Sciences

The process of mediation is of critical importance to the social and behavioral sciences and to evolutionary social psychology in particular. As with the concept of evolutionary adaptation, however, one can argue that causal mediation is in need of explicit theoretical justification and empirical support. Mainstream evolutionary social psychology proposes, for example, that organisms are “adaptation executers”, and not “fitness maximizers”. The execution of adaptations is triggered by fitness-relevant ecological contingencies at both ultimate and proximate levels of analysis. This logic is essentially equivalent to what methodologists refer to as the process of mediation; the adaptations to be executed (or not, depending upon the prevailing environmental circumstances) causally mediate the effects of the ecological contingencies upon the fitness outcomes. Thus, the process of mediation can be generally conceptualized as a causal chain of events leading to a given outcome or set of outcomes. If a predictor variable operates through an intervening variable to affect a criterion variable, then mediation is said to exist. Nevertheless, it does not appear that some psychologists (particularly evolutionary-social psychologists) are sufficiently well-versed in the fundamental logic and quantitative methodology of establishing causal mediation to support such claims. In the current paper, we set out to review the ways researchers support their use of mediation statements and also propose critical considerations on this front. We start with more conventional methods for testing mediation, discuss variants of the conventional approach, discuss the limitations of such methods as we see them, and end with our preferred mediation approach.
GaP-based MIS Capacitors Using a SiN Gate Dielectric

Gallium Phosphide (GaP) Metal-Insulator-Semiconductor (MIS) capacitors were fabricated with synthesized SiN as the gate dielectric. The interface property and the SiN bulk quality were studied with capacitance-voltage (C-V) measurements and current-voltage (I-V) measurements. The total interface state density of 3×1012 cm-2 and the fixed charge density in SiN of 7×1012cm-2 were estimated from the C-V measurements. The leakage current density was as low as 15nA/cm2 at an effective electric field of 3MV/cm. The effective electric field in SiN at breakdown was as high as 10MV/cm. Constant current stress measurements showed bulk trap density of 2×1011 cm-2 in SiN, which is much lower than that for CVD SiN or SiO2.
Analysis of an In-Service Examination for Core Pediatric Craniofacial Surgery Knowledge.

Objective Little is known about designing an effective residency curriculum for pediatric craniofacial surgery. This study elucidates the pediatric craniofacial curriculum of the Plastic Surgery In-Service Training Examination (PSITE) to facilitate knowledge acquisition during residency. Design Approximately, 6 consecutive PSITEs were reviewed for pediatric craniofacial questions (2010-2015). Subjects were categorized according to topics on the American Board of Plastic Surgery written board examination. Questions were categorized using an educational taxonomy model. Answer references were categorized by source and publication lag. Results Of 1174 PSITE questions, 147 tested pediatric craniofacial topics (12.5%). Questions appeared predominately in the Craniomaxillofacial section (83.0%, p Plastic and Reconstructive Surgery (34.5%) was the most cited journal (p Conclusions These data may assist in designating core knowledge competency in pediatric craniofacial surgery for plastic surgery residents. A further understanding of PSITE utility for core knowledge competency in pediatric craniofacial surgery would be the focus of future work.
Multigroup representations of slowing-down kernels in H$sub 2$O

Nonleakage probabilities calculated in multigroup transport and diffusion theory are compared with experimental data. The results are used as a criterion for choosing energy group structures as well as the actual number of groups. In addition, the importance of using the correct type of computer code for generating groups constants is shown. (auth)
Properties of planar electric metamaterials for novel terahertz applications

Planar electric metamaterials are experimentally studied in transmission and reflection utilizing terahertz time-domain spectroscopy. Electrically resonant behavior is observed and provides an estimate of the frequency-dependent transmissivity, reflectivity, and absorptivity of metamaterial composites. Numerical simulations are in good agreement with the measured results and provide additional information helpful in understanding their electromagnetic response. Our results and approach help define the boundaries of a metamaterials-based design paradigm and should prove beneficial in future terahertz applications, particularly with respect to novel filtering, modulation, and switching devices. In addition, this work clarifies some of the mechanisms that limit efficient metamaterials operation at higher-frequencies.
The Philosophy of Taxonomy

One of the tasks of modern philosophy-some philosophers say the only one-is to evaluate the methods and results of the sciences. In this restricted sense, the philosophy of taxonomy means the philosophical basis of taxonomy, or a critique of taxonomy, or a consideration of the validity of taxonomy. For, be it noted, validity and non-validity are attributes of a science as well as a nomenclature. The philosophy of science has been for decades an important and intensively cultivated field, and the special problems of various sciences, like the general subject, have been given careful and repeated study. But in that part of the literature that I have been able to read-there is more than anyone but a full-time philosopher could cover-I find no consideration of the philosophy of taxonomy. The conclusion is inescapable that taxonomists know a good deal more about philosophy than even the scientific philosophers know about the special problem of taxonomy. And yet there is a problem, and it deserves an answer. If the philosophers will not provide it, the taxonomists must try their hand at the job. As a matter of fact, entirely satisfactory and reliable work can be done in taxonomy, as in other sciences, without philosophy. But there are times when we need to know what we are doing and why; and then we are faced with the philosophical problem. The nudge toward philosophy may come from within, as it did to one of our ablest associates in this society, who one day looked around his office and his books and said, approximately, "This is a pretty funny job for an able-bodied man." Or it may be external, provided by someone like my former associate Professor Legree, who declared that taxonomy doesn't matter, ecology doesn't matter, physiology doesn't matter, but pathology is different: pathology is important. Or the need for a philosophy may come from the work itself, when we encounter such a general matter as the species problem. Sooner or later we ought to understand what we are doing; we ought to have a philosophy of taxonomy. I have spoken of the science of taxonomy, just as one might speak of the science of ecology, or of genetics, because the philosophical prob-
Career redux

How can one design a career when career as an institution is dead? Entrepreneurs have an answer.
Benign Leydig Cell Tumor of the Testis Associated with Human Papillomavirus Type 33 Presenting with the Sign of Leser-Trélat

AbstractWe present a case of a benign testicular Leydig cell tumor and eruptive seborrheic keratosis associated with human papillomavirus type 33 infection. To our knowledge this is the first occurrence of a Leydig cell tumor in a patient with tuberous sclerosis and the second documented case of eruptive seborrheic keratoses (sign of Leser-Trelat) associated with a benign neoplasm.
Effects of Patriotism and Celebrity Endorsement in Military Advertising

ABSTRACTThis study investigates the influence of patriotism and celebrity endorsement on advertising effectiveness. College students (N = 201) participated in a 2 × 2 (patriotism: high vs. low × congruence between a celebrity and the military: high vs. low) experiment. To manipulate the subjects' patriotism levels, two video clips were used and to induce congruence, two versions of U.S. Army advertisements were created. The results indicate that patriotism and congruence combined affect advertising effectiveness by increasing favorable attitudes toward military advertising, attitudes toward the military, and behavioral intentions to provide positive word of mouth (WOM) regarding the military.
Gene and Network Analysis of Common Variants Reveals Novel Associations in Multiple Complex Diseases.

Genome-wide association (GWA) studies typically lack power to detect genotypes significantly associated with complex diseases, where different causal mutations of small effect may be present across cases. A common, tractable approach for identifying genomic elements associated with complex traits is to evaluate combinations of variants in known pathways or gene sets with shared biological function. Such gene-set analyses require the computation of gene-level P-values or gene scores; these gene scores are also useful when generating hypotheses for experimental validation. However, commonly used methods for generating GWA gene scores are computationally inefficient, biased by gene length, imprecise, or have low true positive rate (TPR) at low false positive rates (FPR), leading to erroneous hypotheses for functional validation. Here we introduce a new method, PEGASUS, for analytically calculating gene scores. PEGASUS produces gene scores with as much as 10 orders of magnitude higher numerical precision than competing methods. In simulation, PEGASUS outperforms existing methods, achieving up to 30% higher TPR when the FPR is fixed at 1%. We use gene scores from PEGASUS as input to HotNet2 to identify networks of interacting genes associated with multiple complex diseases and traits; this is the first application of HotNet2 to common variation. In ulcerative colitis and waist–hip ratio, we discover networks that include genes previously associated with these phenotypes, as well as novel candidate genes. In contrast, existing methods fail to identify these networks. We also identify networks for attention-deficit/hyperactivity disorder, in which GWA studies have yet to identify any significant SNPs.
Abstract 4429: CCL20 regulation via TGFB /BMP signaling pathway in murine immortalized colonocytes and colonic epithelium

TGFβ and BMP signaling through receptor-mediated activation of SMAD proteins is crucial for normal homeostasis in intestinal epithelium. Alterations in this pathway contribute to the development of colorectal cancers. To understand the role of these pathways in homeostasis of the colon we conditionally deleted loxP-flanked alleles of Smad4 in adult mouse colon. We used Lrig1CreERT allele to achieve greater than 80% SMAD4 gene deletion and a CK19CreERT allele for mosaic deletion in colonic epithelium. Our data indicates that SMAD4 activity regulates multiple interactions between intestinal epithelium cells and surrounding stroma and that deletion of SMAD4 in adult mouse colonic epithelial cells alters expression of cytokines, increases immune cell infiltration and predisposes mice to tumorigenesis. Increases in the chemokine CCL20 have been reported in CRC tumors beginning at the adenoma stage and it may regulate both Tregs and Th-17 cells in an active immune response. Luminex cytokine/chemokine array analysis revealed increased levels of CCL20 protein in colonic mucosa and RNAseq data revealed that when SMAD4 is knocked out in the epithelium there is an upregulation of CCL20 and CCR6 (receptor) mRNA in the epithelium and stroma, respectively. To further explore the regulation of CCL20, we used immortalized mouse colonocytes (IMC cells) to further determine how the TGFβ and BMP signaling pathways may be involved in CCL20 expression. We found that CCL20 mRNA expression was suppressed by TGFβ1 and BMP2 and increased by inhibitors of these pathways. The inhibition of CCL20 by the TGFβ and BMP2 pathways occurs even in the presence of a known strong inducer of CCL20, such as TNFα. We have further observed in mice induced to undergo deletion of SMAD4 in the intestinal epithelium that treatment with DSS results in 100% of mice developing mucinous adenocarcinomas in the distal colon. We conclude that ligand-dependent Smad4-mediated signaling provides important negative homeostatic regulation of CCL20 expression in colonic epithelium. Loss of Smad4 results in increased CCL20 expression and we are currently testing the hypothesis that CCL20 overexpression contributes to the inflammation induced carcinogenesis in this mouse model. Citation Format: Tasia D. Brown, Anna Means, Tanner Freeman, Connie Weaver, Keith Wilson, R. Daniel Beauchamp. CCL20 regulation via TGFB /BMP signaling pathway in murine immortalized colonocytes and colonic epithelium. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4429.
Photoresponse measurement of carbon nanotube based infrared photodetector using digital microscope

The conventional infrared sensors suffer from trade off between sensitivity and cost. The bolometer infrared camera is low resolution and slow speed while the quantum photodetectors are bulky and expensive. In this paper, the novel low dimensional materials carbon nanotube based Schottky barrier structure non cryogenic IR detector was proposed to detect IR irradiance. In order to characterize the photodetector, a testing bench using digital microscope and precise linear stage was used to measure detector performance. The experimental results show the photodetector has negative direction response and positive direction response on right and left side respectively and the maximum photocurrent output depends on the IR irradiance gradient. The proposed measurement method will be applicable for 1D/2D nanoscale material based photodetector characterization.
Mechanistic Studies of the Photoinduced Quinone Trimethyl Lock Decaging Process.

Mechanistic studies of a general reaction that decages a wide range of substrates on exposure to visible light are described. The reaction involves a photochemically initiated reduction of a quinone mediated by an appended thioether. After reduction, a trimethyl lock system incorporated into the quinone leads to thermal decaging. The reaction could be viewed as an electron-transfer initiated reduction of the quinone or as a hydrogen abstraction—Norrish Type II—reaction. Product analysis, kinetic isotope effects, stereochemical labeling, radical clock, and transient absorption studies support the electron transfer mechanism. The differing reactivities of the singlet and triplet states are determined, and the ways in which this process deviates from typical quinone photochemistry are discussed. The mechanism suggests strategies for extending the reaction to longer wavelengths that would be of interest for applications in chemical biology and in a therapeutic setting.
Macro- and Microstructure of the Airways for Drug Delivery

Both anatomy and physiology of the airways are critical for understanding and predicting the dynamics of drug delivery systems that are inhaled. This theme that intimately links the biology of the airways to the response of pulmonary drug delivery systems is present throughout other following chapters in this book. Therefore, it is ideal to introduce these concepts in this chapter by first addressing the lung architecture on the macroscale and how it influences drug delivery. Then, we discuss the microscale interactions between the airway environment and drug delivery system. By discussing the anatomy and physiology at these scales in the direct context of pulmonary drug delivery, we believe this chapter is unique and, hopefully, useful for those seeking the controlled release in the respiratory tract.
W-band SiGe attenuators based on compact low-VSWR topologies

This paper presents two W-Band variable attenuators with low insertion loss and high attenuation range, designed and fabricated in a 0.12 μm SiGe BiCMOS process. The first attenuator is based on a double shunt reverse saturated HBTs topology with two additional impedance transforming sections introduced to maintain a low return loss over the entire W-band for all attenuation states. At 94 GHz, the insertion loss is 2.5 dB, and at the maximum attenuation state loss is 27.8 dB, while S11<-15 dB at 83–110 GHz. Measured input P1dB at 94 GHz is higher than 1 dBm. The second attenuator is based on reflection type topology, obtaining 3.6 dB IL and 22 dB maximum loss. The IC's consume up to 4 mW and occupy areas of 260×270 μm2 and 400×40 μm2, respectively (excluding pads).
Technology Assessment of Boiling Water Reactor Steam Supply Acoustic Performance and Wet Steam Sound Speed

Acoustic oscillations in nuclear steam supplies have caused structural vibration leading to plant modifications in both pressurized water reactor and boiling water reactor (BWR) systems. Power incr...
Does corporate lobbying activity provide useful information to credit markets

Abstract Although corporate lobbying can be motivated for numerous reasons, much of corporate lobbying is aimed to secure public subsidies for the firm's high-risk R&D investment, which aggravates the shareholder-creditor conflict. This paper examines how creditors respond to the firm's lobbying that pursues R&D subsidies. Using syndicated bank loan data, we show that R&D-targeted lobbying activity aggravates shareholder-debtholder conflicts and results in debt rationing, shorter debt maturity, and larger loan spreads. We find weak evidence that creditors also impose tighter covenants. We also show that these effects are generally increasing in the firm's R&D intensity. These results are robust to instrumental variable estimations that endogenizes the decision to lobby by instrumenting cost of lobbying with the number of Electoral College representation in the firm's headquarters state. Further analyses show that R&D-targeted lobbying activity is positively related to the value of equity, suggesting that costs of creditor-imposed restrictions do not dominate the benefits of R&D-targeted lobbying. Overall, our findings suggest that the firm's lobbying activity provides useful incremental information to creditors in resolving informational and adverse selection problems in lending transactions.
Wanting to like: Motivation influences behavioral and neural responses to social feedback

Human beings revel in social approval and social connection. For example, individuals want to be liked, and frequently surround themselves with people who provide such positive reinforcement. Past work highlights a common currency between social rewards like social approval, and non-social rewards like money. But social and motivational contexts can reshape reward experiences considerably. Here, we examine the boundary conditions that deem social approval subjectively valuable. Participants received feedback about their attractiveness from others. Neural activity in reward-related brain structures (e.g., ventral striatum) increased in response to positive feedback, but only when such feedback came from well-liked targets. These heightened reward responses predicted increases in subsequent attraction to well-liked targets. This work suggests that motivational contexts amplify or diminish the value of social approval in a target-specific manner. The value of social approval is thus defined by the extent to which these experiences bring us closer to people we like.
Early progressive mobilization of patients with left ventricular assist devices is safe and optimizes recovery before heart transplantation.

Background As early perioperative survival with left ventricular assist device support improves, additional emphasis must be placed on patient rehabilitation. Especially as mean left ventricular assist device support times exceed 100 days, it is essential for health professionals to mobilize patients to prevent the incidence of the deleterious effects of bedrest. The timing of optimal functional performance and the safety of rehabilitation has not been described. Methods We retrospectively studied patients surviving left ventricular assist device implantation (34 of 41 patients; 27 men, 7 women; age 51 +/- 11 years). Physical therapy consisted of progressive mobilization leading to treadmill exercise or cycling. All patients exercised in the "pump on full" mode with flows >or= 3.0 L/min. Results Twenty of thirty-four patients initiated ambulation at 7 to 10 days with independent ambulation by 14 days in 55% of the group. Treadmill exercise was tolerated by 82% of the patients, begun at postoperative day 21 by eighteen patients. The greatest improvement in exercise performance was seen by 6 to 8 weeks (20 to 30 minutes at 3.17 +/- 0.79 metabolic equivalents). Maximal functional capacity achieved was influenced by medical complications. A total of 1878 treatment sessions lasting 1390 hours was performed. Only four minor incidents occurred representing 2.9 incidents/1000 patient hours; all involved a transient decrease in pump flow. None of these events resulted in an increase in morbidity or mortality. Conclusions Progressive mobilization in patients with left ventricular assist device is safe. Patients return to independence in activities of daily living and tolerate prolonged workloads of up to 5 metabolic equivalents. There is rapid improvement in functional capacity until 6 weeks after operation. Delay in transplantation until this time may optimize postoperative recovery.
Raman and Infrared Microspectroscopy

A thorough description of the instrumental design of instruments combining vibrational spectroscopy with light microscopy (microspectrometers) is presented in this article. Focus is made particularly on Raman and infrared microspectrometry and practical examples are given.
Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis.

Background Despite the high prevalence of frailty among patients receiving hemodialysis, few preventable or treatable contributing causes have been identified. Hypogonadism is also common in this population and low serum testosterone concentrations share several clinical phenotypes with frailty. We hypothesized that low serum testosterone concentrations would be associated with frailty and several of its individual components. Methods We used data from 440 men from A Cohort Study To Investigate the Value of Exercise in ESRD/Analysis Designed to Investigate the Paradox of Obesity and Survival in ESRD, a longitudinal study that recruited participants from 14 dialysis centers in Atlanta, GA and the San Francisco, CA Bay Area from 2009 to 2011. We assessed frailty using the Fried Frailty Phenotype. We examined the association between free testosterone (as a continuous and dichotomous variable) and frailty, individual frailty components, sarcopenia, lower extremity function and muscle mass estimation by creatinine and body impedance spectroscopy over 12 months using generalized estimating equations. Results The mean age was 56.1 ± 14.2 years and 27% were white. A 50% lower concentration of free testosterone was associated with 1.40-fold higher odds of being frail [95% confidence interval (CI) 1.05-1.53] and 1.40-fold higher odds of becoming frail over 12 months (95% CI 1.07-1.73). This association was mainly due to an association with two components of frailty: grip strength and gait speed. In addition, 50% lower free testosterone concentration was associated with a 1.55-fold higher odds of having sarcopenia (95% CI 1.09-2.02) and 1.72-fold higher odds for developing sarcopenia (95% CI 1.13-2.33) as well as with lower muscle mass and a decrease in muscle mass over 12 months as estimated by serum creatinine and by bioelectrical impedance spectroscopy. Conclusion Serum free testosterone concentration was associated with frailty, physical function, sarcopenia and muscle mass as well as with changes in these outcomes over 12 months. Testosterone replacement may be a feasible therapeutic target toward prevention of frailty, although clinical trials are needed to test this possibility.
Propranolol as an effective therapy for infantile haemangioma of the urinary bladder

Infantile haemangiomas are one of the most common tumours in infancy, but typically present as cutaneous lesions; haemangiomas of the urinary bladder are incredibly rare. Although benign, these can sometimes ulcerate and bleed, causing haematuria in the case of bladder lesions. Propranolol is a well-documented medical therapy for cutaneous lesions, but surgical treatment dominates the literature on bladder haemangiomas. We present the case of a child with infantile haemangiomas of the urinary bladder, as well as internal and cutaneous lesions, treated with propranolol. At 6-week follow-up cystoscopy and MRI, there was a significant improvement in both bladder and internal lesions, respectively. Follow-up with dermatology 9 months after initiation of propranolol demonstrated excellent regression of the cutaneous lesions with a marked decrease in both size and prominence. This case demonstrates the potential role of propranolol in the treatment of bladder haemangiomas in lieu of more invasive surgical techniques.
Parental Perspectives on Roles in End-of-Life Decision Making in the Pediatric Intensive Care Unit: An Integrative Review.

Abstract Problem Little is known about how parents perceive their role or the role of health care providers (HCPs) during end-of-life decision making (EOL DM) in the context of the pediatric intensive care unit (PICU). Eligibility criteria The authors searched CINAHL, PubMed, Ovid Medline, Web of Science, Social Science Database, PsycINFO, and Google scholar for English language studies performed in the United States related to parental perception of parental or HCP roles in EOL DM in the PICU since 2008. Sample Eleven studies of parents and health care providers (HCPs) of critically ill children in the PICU and/or receiving inpatient pediatric palliative care, and bereaved parents of PICU patients. Results Most parents reported belief that EOL DM is within the domain of parental role, a minority felt it was a physician's responsibility. Parental EOL DM is rooted more firmly in emotion and perception and a desire to be a ‘good parent’ to a child at EOL in the way they see fit than HCP recommendations or ‘medical facts’. Parents need HCPs to treat them as allies, communicate well, and be trustworthy. Conclusions Role conflict may exist between parents and HCPs who are prioritizing different attributes of the parental role. The role of the nurse in support of parental role in the PICU is not well-elucidated in the extant literature. Implications Future research should focus on what parents need from HCPs, especially nurses, to support their parental role, and factors that facilitate the development of trust and good communication.
User Authentication from Web Browsing Behavior

Abstract : As anticipated in True Names by Vernor Vinge, identity has been recognized as our most valued possession in cyberspace. Attribution is a key concept in enabling trusted identities and deterring malicious activities. As more people use the Web to communicate, work, and otherwise have fun, is it possible to uniquely identify someone based on their Web browsing behavior or to differentiate between two persons based solely on their Web browsing histories? Based on a user study, this paper provides some insights into these questions. We describe characteristic features of Web browsing behavior and present our algorithm and analysis of an ensemble learning approach leveraging from those features for user authentication.
Effects of body condition score on direct and indirect measurements of insulin sensitivity in periparturient dairy cows

Reductions in insulin sensitivity in periparturient dairy cows develop as a means to support lactation; however, excessive mobilization of fatty acids (FA) increases the risk for peripartal metabolic disorders. Our objectives were to investigate the effect of prepartum body condition score (BCS) on systemic glucose and insulin tolerance, and to compare direct and indirect measurements of insulin sensitivity in peripartal lean and overweight dairy cows. Fourteen multiparous Holstein cows were allocated into two groups according to their BCS at day -28 prepartum: lean (n = 7; BCS ≤ 3.0) or overweight; (n = 7; BCS ≥ 4.0). Liver biopsies were performed on day -27, -14 and 4, relative to expected parturition. Intravenous insulin or glucose tolerances tests were performed following each liver biopsy. Relative to lean cows, overweight cows exhibited lower dry matter intake, lost more BCS and displayed increased plasma FA and β-hydroxybutyrate concentrations and elevated liver lipid content during peripartum. Glucose clearance rate was lower for all cows postpartum. Prepartum BCS had minimal effects on insulin and glucose tolerance; however, the ability of the cow to restore blood glucose levels following an insulin challenge was suppressed by increased BCS. Glucose-dependent parameters of insulin and glucose tolerance were not correlated with surrogate indices of insulin sensitivity. We conclude that prepartum BCS had minimal effect on systemic insulin sensitivity following parturition. The observed inconsistency between surrogate indices of insulin sensitivity and direct measurements of insulin and glucose tolerance adds support to growing concerns regarding their usefulness as tools to estimate systemic insulin action in periparturient cows.
Branching Fractions of the $X(3872)$

The recoil momentum spectrum from the decay $B^+ \to K^+ +\mathrm{anything}$ has recently been measured by the BaBar collaboration. The spectrum has a peak with invariant mass near the mass of the $X(3872)$ meson. The preliminary measurement by the BaBar collaboration implies that its branching fraction into $J/\psi\, \pi^+\pi^-$ is about 4\%. We emphasize that this is the branching fraction for the entire resonance feature from $B^+$-to-$K^+$ transitions, which includes a $D^{*0} \bar D^0$ and $D^0 \bar D^{*0}$ threshold enhancement as well as a possible bound state below the threshold or a virtual state. If the $X$ is a bound state of charm mesons, its branching fraction into $J/\psi\, \pi^+\pi^-$ should be considerably larger than that of the $X$ resonance feature. We use measurements of branching ratios of the $X$ to put an upper bound on this branching fraction of 33\%. We also constrain the parameters of the simplest plausible model for the line shapes of the $X$ using the precise measurement of the resonance energy of the $X$ and an estimate of the branching fraction into $D^0 \bar D^0 \pi^0$ and $D^0 \bar D^0\gamma$ from the $X$ resonance feature from $B^+$-to-$K^+$ transitions.
Resolution-invariant measurements of small objects in polychromatic CT data

Features such as particles, pores, or cracks are challenging to measure accurately in CT data when they are small relative to the data resolution, characterized as a point-spread function (PSF). These challenges are particularly acute when paired with segmentation, as the PSF distributes some of the signal from a voxel among neighboring ones; effectively dispersing some of the signal from a given object to a region outside of it. Any feature of interest with one or more dimensions on the order of the PSF will be impacted by this effect, and measurements based on global thresholds necessarily fail. Measurements of the same features should be consistent across different instruments and data resolutions. The PVB (partial volume and blurring) method successfully compensates by quantifying features that are small in all three dimensions based on their attenuation anomaly. By calibrating the CT number of the phase of interest (in this case, gold) it is possible to accurately measure particles down to <6 voxels in data acquired on two instruments, 14 years apart, despite severe artifacts. Altogether, the PVB method is accurate, reproducible, resolution-invariant, and objective; it is also notable for its favorable error structure. The principal challenge is the need for representative effective CT numbers, which reflect not only the features of interest themselves, but also the X-ray spectrum, the size, shape and composition of the enclosing sample, and processing details such as beam-hardening correction. Empirical calibration is the most effective approach.
The Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. As a tumor that predictably develops in patients with known underlying liver disease, mostly in cirrhosis, it is imperative that effective screening and surveillance strategies be implemented to identify the disease at a stage when it is curable. For early stage cirrhotic patients without prohibitive portal hypertension and with compensated liver function, surgical resection is the goal. Locoregional therapies include ablative, transarterial, and radiation-based therapies, which have a critical role in controlling the tumor, and may allow for unresectable patients with disease confined to the liver to be bridged or downstaged prior to curative-intent liver transplantation, unequivocally the gold-standard treatment for early stage patients with unresectable HCC. For locally advanced and metastatic HCC patients who are not candidates for locoregional or surgical therapy, the last few years have seen many successes with the approval of numerous targeted therapies and immunotherapies in both front line and second line. With an increasing characterization of the underlying genomic, transcriptomic, proteomic, and epigenetic aberrations that impact HCC tumor biology, there is renewed hope for the discovery of additional targeted therapies to treat tumor recurrence and allow for precision oncology approaches to patients with this deadly malignancy.
The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.
National Trends and Variation of Functional Status Deterioration in the Medically Critically Ill.

OBJECTIVES Physical and psychologic deficits after an ICU admission are associated with lower quality of life, higher mortality, and resource utilization. This study aimed to examine the prevalence and secular changes of functional status deterioration during hospitalization among nonsurgical critical illness survivors over the past decade. DESIGN We performed a retrospective longitudinal cohort analysis. SETTING Analysis performed using the Cerner Acute Physiology and Chronic Health Evaluation outcomes database which included manually abstracted data from 236 U.S. hospitals from 2008 to 2016. PATIENTS We included nonsurgical adult ICU patients who survived their hospitalization and had a functional status documented at ICU admission and hospital discharge. Physical functional status was categorized as fully independent, partially dependent, or fully dependent. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Functional status deterioration occurred in 38,116 patients (29.3%). During the past decade, functional status deterioration increased in each disease category, as well as overall (prevalence rate ratio, 1.15; 95% CI, 1.13-1.17; p < 0.001). Magnitude of functional status deterioration also increased over time (odds ratio, 1.03; 95% CI, 1.03-1.03; p < 0.001) with hematological, sepsis, neurologic, and pulmonary disease categories having the highest odds of severe functional status deterioration. CONCLUSIONS Following nonsurgical critical illness, the prevalence of functional status deterioration and magnitude increased in a nationally representative cohort, despite efforts to reduce ICU dysfunction over the past decade. Identifying the prevalence of functional status deterioration and primary etiologies associated with functional status deterioration will elucidate vital areas for further research and targeted interventions. Reducing ICU debilitation for key disease processes may improve ICU survivor mortality, enhance quality of life, and decrease healthcare utilization.
Black Birth Outcomes and Implications for Counseling

Black women experience disparate rates of adverse birth outcomes in the United States. Empirical evidence suggests that Black women’s distinct socio-cultural experiences yield complex clusters of s...
Epistemic engagement: examining personal epistemology and engagement preferences with climate change in Oregon

Engaging politically polarized publics surrounding climate science is a vital element in the effort to enact climate mitigation policy. Science communication experts have identified several models of public engagement with science, including the deficit, dialogue, participation, and lay expertise model. Existing research suggests that the deficit model in particular is a largely ineffective model of engagement for controversial science like climate change. There is very little research, however, regarding the engagement preferences of political groups, or how those preferences differ. This study assesses preferences for climate change engagement in the state of Oregon in the United States and examines the relationship between those preferences and epistemic beliefs about climate science. Overall, we find that liberals are significantly more likely than moderates or conservatives to view climate science as certain and simple and to rely on expert knowledge more than their own direct experience. By contrast, conservatives are significantly more likely than liberals or moderates to view climate science as uncertain and complex and to rely on their own direct experience over the knowledge of content experts. We also find that perceived certainty and simplicity are positive predictors of a preference for the deficit model of science communication. Implications for public engagement with climate change and suggestions for future research are discussed.
Anomalous Absorption in Fluctuating Valence Compounds

We have shown for the first time that fluctuating valence compounds have a characteristic broad absorption maximum in the far infrared. The absorptivity peak near 150 cm−1 in CePd 3 , absent in the isostructural compound YPd 3 , arises from fluctuations of the cerium ion valence between the 3+ and 4+ state.
Inducing homologous recombination deficiency using AVB500, a receptor tyrosine kinase AXL inhibitor in uterine serous cancer (USC)

Objectives: Homologous recombination deficiency (HRD) is more common in non-endometrioid TP53-mutant endometrial cancers. Given this, our objective was to assess whether two USC cell lines were homologous recombination proficient (HRP) and to determine whether HRD could be induced with inhibition of the GAS6/AXL pathway with AVB-500 in uterine serous cancer. Methods: Baseline homologous recombination (HR) status of uterine serous cancer cell lines, ARK1 and ARK4 was determined after inducing DNA damage with 10Gy of radiation treatment (RT). We then identified both gamma-H2AX, a marker of DNA damage, and RAD51 foci, a marker signifying intact DNA double strand break repair, by immunofluorescence (IF). RAD51 foci from both radiated and non-radiated cells were quantified in both cell lines. Cell lines were considered to be HRP if over 30% of the cells expressed RAD51 (>5 foci per cell) after a DNA damage event. IF was conducted using a Leica confocal microscope and foci were quantified using FociCounter. Results: Radiated cells expressed more gamma-H2AX foci in both ARK1 (11.0 vs 0.4, p Conclusions: Our objective was to assess HR status in ARK1 and ARK4 and if HRP, to test whether HRD could be induced with inhibition of the GAS6/AXL pathway with AVB-500. Pretreatment with AVB-500 led to a decrease in RAD51 foci, and in the ARK1 cell line induced HR deficiency. Additional therapeutic and mechanistic experiments are ongoing.
Synthesis and Characterization of a Low-Molecular-Weight Novolac Epoxy Derived from Lignin-Inspired Phenolics.

The need for renewable polymers capable of replacing their petrochemical counterparts continues to grow as sustainability concerns rise. Bisguaiacol (BG), a bioinspired alternative to bisphenol-A (BPA), has been synthesized using vanillyl alcohol and guaiacol via an electrophilic aromatic condensation. Purification provides both BG and an oligomeric coproduct with a consistent number average molecular weight and dispersity of ∼650 Da and ∼1.00, respectively. This coproduct has been well characterized as a low-molecular-weight novolac averaging five hydroxyls per molecule and was transformed into an epoxy resin suitable for use in thermosetting resins. The bioinspired thermoset produced in this work, consisting of the epoxidized coproduct and an amine curing agent (Epikure W), exhibited a glass transition temperature over 100 °C and glassy storage modulus value of ∼3 GPa at 25 °C. When compared to a commercial cresol novolac epoxy, the cured epoxidized coproduct resin shows comparable thermal and thermomechanical properties. When compared to a commercial BPA-based resin, the cured epoxidized coproduct resin shows improved mode 1 fracture values of 1.34 J m1/2 (K1C) and 448.16 J/m2 (G1C). By utilizing the coproduct strategically, the overall production of BG has the potential to become more economically feasible.
Host-Pathogen Interactions of Chlamydia trachomatis in Porcine Oviduct Epithelial Cells.

Chlamydia trachomatis (Ct) causes the most prevalent bacterial sexually transmitted disease leading to ectopic pregnancy and infertility. Swine not only have many similarities to humans, but they are also susceptible to Ct. Despite these benefits and the ease of access to primary tissue from this food animal, in vitro research in swine has been underutilized. This study will provide basic understanding of the Ct host–pathogen interactions in porcine oviduct epithelial cells (pOECs)—the counterparts of human Fallopian tube epithelial cells. Using NanoString technology, flow cytometry, and confocal and transmission-electron microscopy, we studied the Ct developmental cycle in pOECs, the cellular immune response, and the expression and location of the tight junction protein claudin-4. We show that Ct productively completes its developmental cycle in pOECs and induces an immune response to Ct similar to human cells: Ct mainly induced the upregulation of interferon regulated genes and T-cell attracting chemokines. Furthermore, Ct infection induced an accumulation of claudin-4 in the Ct inclusion with a coinciding reduction of membrane-bound claudin-4. Downstream effects of the reduced membrane-bound claudin-4 expression could potentially include a reduction in tight-junction expression, impaired epithelial barrier function as well as increased susceptibility to co-infections. Thereby, this study justifies the investigation of the effect of Ct on tight junctions and the mucosal epithelial barrier function. Taken together, this study demonstrates that primary pOECs represent an excellent in vitro model for research into Ct pathogenesis, cell biology and immunity.
The effect of superimposed low-frequency modulation on lubrication in machining

A study has been made of the effect of an externally imposed, low-frequency modulation on the action of lubricants in machining. It is shown that in conventional machining, lubricant action is essentially confined to the edges of the chip-tool contact, with little or no change in the friction condition over much of the rake face. However, the effectiveness of lubricant action is significantly enhanced when a controlled low-frequency modulation of sufficient amplitude is imposed in the direction of cutting. Measurements show that the friction coefficient on the rake face is reduced by a factor of two to three in the presence of such a modulation. The nature of metal transfer onto the rake face is also substantially changed by the modulation.
Role of Apical Ion Channels in Sour Taste Transduction

Sour taste perception depends primarily on the concentration of H+ in the taste stimulus. Acid stimuli elicit concentration-dependent action potentials in taste cells. Recent patch-clamp studies suggest that protons depolarize taste cells by direct interaction with apically located ion channels. In Necturus maculosus, the voltage-dependent K+ conductance is restricted to the apical membrane of taste cells. The current flows through a variety of K+ channels with unitary conductances ranging from 30 to 175 pS, all of which are blocked directly by citric acid applied to outside-out or perfused cell-attached patches. In contrast, hamster fungiform taste cells appear to utilize the amiloride-sensitive Na+ channel for acid transduction. Amiloride completely inhibits H+ currents elicited by acid stimuli in isolated taste cells, with an inhibition constant similar to that for amiloride-sensitive Na+ currents (Ki = 0.2 microM). Treatment of isolated taste cells with the bioactive peptide arginine-vasopressin results in similar increases in both the amiloride-sensitive Na+ and H+ currents; the effect is mimicked by 8-bromocyclic AMP. These results suggest that H+ can permeate amiloride-sensitive Na+ channels in hamster fungiform taste cells, contributing to the transduction of sour stimuli.