cssi/SciSciGPT-SciSciNet huggingface dataset:
Dual HER2 blockade: preclinical and clinical data

The estrogen receptor and human epidermal growth factor receptor (HER) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Not surprisingly, targeting these pathways provides the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment. By increasing the understanding of the molecular mechanisms of combined HER2-targeted therapies, we aim to be better able to select patients who would respond to these treatments and understand some of the mechanisms of resistance to HER2-targeted treatments. Recent studies have demonstrated an increased effectiveness of dual targeted HER2 therapies against HER2-amplified breast cancer as compared with single blockade. These studies have resulted in the recent US Food and Drug Administration approval of the combination of taxane chemotherapy with pertuzumab and trastuzumab in the first-line metastatic setting as well as an accelerated approval in the neoadjuvant setting. Another mechanism for overcoming resistance to HER2 targeted therapies is the antibody-drug conjugate trastuzumab-emtansine, which targets the HER2 receptor conjugated to the potent antimicrotubule agent mertansine, allowing for intracellular release of the cytotoxic drug. Studies evaluating the efficacy of dual blockade with antibody-drug conjugate are currently ongoing. This article reviews recent data on different combinations of anti-HER2 treatments as well as ongoing and future research in this area.
Payload length and rate adaptation for multimedia communications in wireless LANs

We provide a theoretical framework for cross-layer design in multimedia communications to optimize single-user throughput by selecting the transmitted bit rate and payload size as a function of channel conditions for both additive white Gaussian noise (AWGN) and Nakagami-m fading channels. Numerical results reveal that careful payload length adaptation significantly improves the throughput performance at low signal to noise ratios (SNRs), while at higher SNRs, rate adaptation with higher payload lengths provides better throughput performance. Since we are interested in multimedia applications, we do not allow retransmissions in order to minimize latency and to reduce congestion on the wireless link and we assume that packet loss concealment will be used to compensate for lost packets. We also investigate the throughput and packet error rate performance over multipath frequency selective fading channels for typical payload sizes used in voice and video applications. We explore the difference in link adaptation thresholds for these payload sizes using the Nafteli Chayat multipath fading channel model, and we present a link adaptation scheme to maximize the throughput subject to a packet error rate constraint.
Statistical Analysis of the Uncertainties in Cloud Optical Depth Retrievals Caused by Three-Dimensional Radiative Effects

Abstract This paper presents a simple yet general approach to estimate the uncertainties that arise in satellite retrievals of cloud optical depth when the retrievals use one-dimensional radiative transfer theory for heterogeneous clouds that have variations in all three dimensions. For the first time, preliminary error bounds are set to estimate the uncertainty of cloud optical depth retrievals. These estimates can help us better understand the nature of uncertainties that three-dimensional effects can introduce into retrievals of this important product of the Moderate Resolution Imaging Spectroradiometer instrument. The probability distribution of resulting retrieval errors is examined through theoretical simulations of shortwave cloud reflection for a set of cloud fields that represent the variability of stratocumulus clouds. The results are used to illustrate how retrieval uncertainties change with observable and known parameters, such as solar elevation or cloud brightness. Furthermore, the results i...
Rabbit arthritis induced by cell-free extracts of erysipelothrix.

Abstract A cell-free crude extract of Erysipelothrix rhusiopathiae injected intravenously in rabbits induced pathological lesions of the synovial tissue similar to the lesions seen in rheumatoid arthritis. Fluorescence techniques utilizing tagged specific antiserum and fluorescent-tagged antigen injected into nonsensitized rabbits demonstrated the localization of antigen exclusively in the synovium. Localized concentration of fluorescence was demonstrated as early as 1 hr after injection, before histological changes were apparent. After 48 hr, the fluorescence was concentrated in focal areas and early pathological changes characterized as “mesenchymal activation” were observed. A consideration of the significant role of exogenous antigen in the sensitivity arthritides is discussed.
Comparison of deceptive and truthful travel reviews

As the use of online reviews grows, so does the risk of providers trying to influence review postings through the submission of false reviews. It is difficult for users of online review platforms to detect deception as important cues are missing in online environments. Automatic screening technologies promise a reduction in the risk but need to be informed by research as to how to classify reviews as suspicious. Using findings from deception theory, a study was conducted to compare the language structure of deceptive and truthful hotel reviews. The results show that deceptive and truthful reviews are different in terms of lexical complexity, the use of first person pronouns, the inclusion of brand names, and their sentiment. However, the results suggest that it might be difficult to distinguish between deceptive and truthful reviews based on structural properties.
Reliability and validity of the Yale-Brown Obsessive-Compulsive Scale

The reliability and validity of the Yale-Brown Obsessive-Compulsive Scale were examined according to a multi-trait multi-method approach in a sample of 54 outpatients with obsessive-compulsive disorder (OCD). Internal consistency was acceptable but was improved by deletion of items concerning resistance to obsessions and compulsions. Inter-rater reliability was excellent, but test-retest reliability over an average interval of 48.5 days was lower than desirable. The YBOCS demonstrated good convergent validity with most other measures of OCD, but divergent validity vis a vis depression was poor. Analyses of new items assessing avoidance and the duration of obsession-free and compulsion-free intervals indicated that only the avoidance rating added meaningfully to the full scale score. In future research the authors recommend deletion of the resistance items and inclusion of the avoidance item to yield a revised 9-item YBOCS total score.
Genes and Pain

The Genetics of Pain is an extensive review of the relationship between genetics and pain by a distinguished group of authors and edited by a leader in this field, Jeffrey Mogil, PhD. The premise for this volume is that the explosion in basic science knowledge regarding pain mechanisms has not yet successfully translated to the clinic. Thanks in part to the sequencing of the human genome and the development of powerful new methods, genetic techniques are now readily applied to problems of pain and hold promise for identifying new molecular targets from which more efficacious and safer analgesics can be developed. This important volume provides a description of genetic techniques and reviews new knowledge that has resulted from research on the genetic contributions to pain in animal models and humans. Also covered is the contribution of
The E2F functional analogue SBF recruits the Rpd3(L) HDAC, via Whi5 and Stb1, and the FACT chromatin reorganizer, to yeast G1 cyclin promoters

Regulation of the CLN1 and CLN2 G1 cyclin genes controls cell cycle progression. The SBF activator binds to these promoters but is kept inactive by the Whi5 and Stb1 inhibitors. The Cdc28 cyclin-dependent kinase phosphorylates Whi5, ending the inhibition. Our chromatin immunoprecipitation (ChIP) experiments show that SBF, Whi5 and Stb1 recruit both Cdc28 and the Rpd3(L) histone deacetylase to CLN promoters, extending the analogy with mammalian G1 cyclin promoters in which Rb recruits histone deacetylases. Finally, we show that the SBF subunit Swi6 recruits the FACT chromatin reorganizer to SBF- and MBF-regulated genes. Mutations affecting FACT reduce the transient nucleosome eviction seen at these promoters during a normal cell cycle and also reduce expression. Temperature-sensitive mutations affecting FACT and Cdc28 can be suppressed by disruption of STB1 and WHI5, suggesting that one critical function of FACT and Cdc28 is overcoming chromatin repression at G1 cyclin promoters. Thus, SBF recruits complexes to promoters that either enhance (FACT) or repress (Rpd3L) accessibility to chromatin, and also recruits the kinase that activates START.
The acquisition of /r/ and /l/ by Japanese learners of English: Evidence that speech production can precede speech perception

This study examines the relationship between the production and perception of English /r/ and /l/ by native Japanese adults learning English in the United States. For some subjects, production of the contrast was more accurate than their perception of it, replicating and extending a previous finding reported by Goto (1971) in Japan. The difficulty in perception of the liquid contrast varied with its position in the word. Prevocalic /r/ and /l/ in consonant clusters yielded the greatest perceptual errors, while word-final liquids were accurately perceived. This pattern of errors is not predictable on the basis of contrastive phonological analysis, but might be the result of acoustic-phonetic factors. Implications for second language pedagogy are discussed.
Splitting the Gene: DNA Patents and the Genetic Code

This Article addresses the intersection of DNA and the patent system. An inquiry into DNA as patentable subject matter must consider the static and dynamic properties of the gene, the unit of DNA which is the focus of most patenting efforts and most controversy. The Article sets forth a theory of the gene for patent law that encompasses its dual identities of chemical and template, in effect, a splitting of the gene. The gene is both the static chemical compound and the dynamic template executed through the genetic code. While this definition can be accommodated as a statement of scientific reality, it has a particular impact on the legitimacy of the gene as a unit of intellectual property. The duality of DNA requires a bifurcated legal analysis that draws on both product-based and process-based doctrines of eligibility developed in patentable subject matter jurisprudence to derive analytic principles suitable for the complexity of the DNA molecule. This Article undertakes that analysis with reference to the patent jurisprudence for products of nature, laws of nature, natural phenomena, and computer algorithms. A public domain is explicitly recognized in patent law by judicial exclusion of the laws of nature, natural phenomena, and abstract ideas from patent protection. The scrutiny of DNA from the perspective of its duality suggests that, although DNA can be characterized as a chemical compound for potential eligibility into the private domain of patents, its identity as a template executed through the genetic code reveals attributes with public domain requirements. By scientific and historical criteria, the genetic code can be characterized as a law of nature and as an essential component of the public domain in molecular biology. The Article concludes that the patenting of genes results in constructive preemption of the genetic code, a result that is contrary to the Supreme Court's dictate that the laws of nature are not patentable. This outcome undermines the legitimacy of genes as patentable subject matter.
Choice-based Pricing for User-Provided Connectivity?

User-provided connectivity (UPC) leverages the network connectivity of its users to build a service offering that goes beyond their individual connectivity option, i.e., allows them to roam. Because the service's overall value typically grows as a function of its coverage, it is important to devise pricing policies that make it attractive to all users, even those who derive little value from roaming. This paper builds on earlier work that explored the value of a UPC service, and proposes a new pricing policy, the Price choice policy, that seeks to realize an effective compromise between pricing complexity and the policy's ability to maximize system value and extract profit. The paper illustrates the benefits of the proposed policy by demonstrating why and how it outperforms several previously proposed policies.
A pragmatic randomized trial comparing tablet computer informed consent to traditional paper-based methods for an osteoporosis study.

Abstract Objective Methods to improve informed consent efficiency and effectiveness are needed for pragmatic clinical trials. We compared informed consent using a tablet computer to a paper approach to assess comprehension and satisfaction of patients and clinic staff for a future osteoporosis clinical trial. Methods Nine community-based practices identified and recruited patients to compare the informed consent processes (tablet vs. paper) in a mock osteoporosis clinical trial. The tablet informed consent included an animation summarizing the trial, complete informed consent document, and questions to assess and reinforce comprehension of the study. Participants were women age ≥55 years with ≥1 year of alendronate use. We surveyed participants to assess comprehension and satisfaction and office staff for satisfaction and perceived time demands. Results The nine practices enrolled 33 participants. There was not a significant difference in comprehension between the tablet vs. paper informed consent [mean (SD) tablet: 12.2 (1.0) vs. paper: 11.4 (1.7)]. Office staff preferred the tablet to the paper informed consent for identifying potential study participants (two-sided t-test p = 0.02) despite an increased perceived time spent to complete the tablet process [tablet: 28.3 min (SD 16.3) vs. paper: 19.0 min (SD 6.9); p = 0.08]. Conclusions Although, there were no significant differences in participant satisfaction and comprehension with the tablet informed consent compared to a paper informed consent, patients and office staff trended towards greater satisfaction with the tablet informed consent. Larger studies are needed to further evaluate the utility of electronic informed consent in pragmatic clinical trials.
Abstract 353: Hdac Class I Inhibition Diminished Cd90+ Cardiac Fibroblast Activation Via Gsk3b/β-catenin Pathway.

Myofibroblast activation is one of the major mechanisms of scar formation and interstitial myocardial fibrosis after myocardial infarction (MI) and subsequent heart failure. Elucidating the mechanisms of myofibroblast activation will provide a strategy to treat heart failure. Histone Deacetylases (HDAC) were reported to regulate myofibroblast differentiation and extracellular matrix deposition in lung, kidney and liver fibrosis. Furthermore, HDAC inhibitors were shown to retard myocardial remodeling, interstitial fibrosis and improve cardiac function after MI. However, the mechanisms are unclear. Here we examined whether HDAC1/2 are up-regulated after MI, identify which myocardial cell type is predominately expressing HDAC, and examine the effects of HDAC inhibition on myocardial fibrosis. MI was created in rats by ligation of the left coronary artery. We found that, in sham rats, HDACs were uniformly expressed in both right and left ventriculars. On the other hand, we observed up-regulation of both HDAC1 and 2 in the infarcted LV following MI. In addition, HDAC1 and 2 were co-localized with cardiac fibroblast markers CD90, Vimentin, and αSMA in the infarcted area. Treatment of CD90+ cells isolated from both CHF and sham atrial culture with pan HDAC inhibitor (100 nM, or 300 nM) TSA diminished cardiac fibroblasts activation as indicated by the decrease in αSMA and the increase in E-cadherin gene expressions. Similarly, treatment of CD90 cells with a specific HDAC class I inhibitor (2 μM, Mocetinostat) upregulated E-cadherin and diminished the markers of fibrosis (αSMA, MMP-2, and Collagen III).The decrease in fibroblast activation by HDAC inhibition was associated with increase in p-Gsk3β/Gsk3β ratio and β-catenin protein content. In addition, Mocetinostat treatment of CD90+ cells up-regulated cleaved-Caspase3, an indicator of apoptosis. Taken together, diminishing cardiac fibroblast activation using HDAC class I inhibitor appears to be dependent on Gsk3β/β-catenin pathway.
MsaB Activates Capsule Production At the Transcription Level In Staphylococcus aureus

Staphylococcus aureus produces several virulence factors that allow it to cause a variety of infections. One of the major virulence factors is the capsule, which contributes to the survival of the pathogen within the host as a way to escape phagocytosis. The production of the capsular polysaccharide is encoded in a 16 gene operon, which is regulated in response to several environmental stimuli including nutrient availability. For instance, the capsule is produced in the late- and post-exponential growth phases, but not in the early- or mid-exponential growth phase. Several regulators are involved in capsule production, but the regulation of the cap operon is still poorly understood. In this study, we show that MsaB activates the cap operon by binding directly to a 10 bp repeat in the promoter region. We show that despite the fact that MsaB is expressed throughout four growth phases, it only activates capsule production in the late- and post-exponential growth phases. Furthermore, we find that MsaB does not bind to its target site in the early and mid-exponential growth phases. This correlates with decreased nutrient availability and capsule production. These data suggest either that MsaB binding ability changes in response to nutrients or that other cap operon regulators interfere with the binding of MsaB to its target site. This study increases our understanding of the regulation of capsule production and the mechanism of action of MsaB.
Isolation of Herpesviruses from Trigeminal Ganglia of Man, Monkeys, and Cats

Herpes simplex virus was isolated from the trigeminal ganglia of four out of 10 autopsied patients with no clinical evidence of herpes; the ganglia had been removed within 10 hr of death. The isolates appeared to be similar to type 1 virus from the points of view of antigenicity and cytopathic effect. As was the case when herpesviruses were isolated from the central nervous system of experimentally infected rabbits, relatively few of the tissue cultures inoculated with the ganglion cells yielded virus. A herpesvirus was isolated from the trigeminal ganglia of one of 10 squirrel monkeys, at least seven of which had antibody to this virus. No herpesvirus could be isolated from the trigeminal ganglia or the first three pair of sacral ganglia of 20 cats, at least half of which had been naturally infected with the herpesvirus of cats (feline rhinotracheitis virus), as indicated by neutralizing antibody in the sera of the cats. The persistence of varicella-zoster virus in the posterior sensory ganglia has long been suspected because of the inflammatory reaction of such ganglia during zoster and because of the frequent involvement of the same ganglion in individuals developing shingles on two separate occasions [1]. The trigeminal ganglia have been suggested as the site of persistence of herpes simplex virus, a hypothesis supported to some extent by the frequent appearance of herpes lesions on the denervated area of the face within a short time of surgical section of the trigeminal nerve root [2], and by the recent recovery of herpes simplex virus from the trigeminal ganglia of autopsied patients [3, 4]. The ability of herpes simplex viruses types 1 and 2 to persist in the central nervous system (CNS) or in the associated dorsal ganglia, including the trigeminal ganglia, of experimentally infected rabbits is well established [5-7]. In fact, several of the herpesviruses seem to show an affinity for the sensory
Phoma Conidiogena on Box

A distinctive leaf tip blight of two bushes of Buxus sempervirens var. angustifolia Linn. was noted in the late summer of 1930 in The New York Botanical Garden boxwood collection. The leaves of the current year's growth, as well as older ones, were affected. The necrotic area was always at the extreme tip of the leaf and contrasted markedly with the healthy portion because of its ashy gray color and very thin texture. It was separated from the green portion of the leaf by a very narrow dark band made up of alternating gray, black and brown lines (plate 4, a). Small dark brown to black ostiolate pycnidia were scattered irregularly on both surfaces of the dead area (plate 4, b, c). In October of the same year the trouble was observed in an? other planting considerably removed from the first. The only variety affected was again Buxus sempervirens var. angustifolia. Spores from these plants were still viable in February, 1931, after having weathered winter conditions. The bushes on which the fungus was first seen again furnished abundant material in the spring of 1931, but only on old leaves. Not until September was the new growth found affected. The fungus is not confined to the leaves, but was also found in defoliated dying twigs. Fruit bodies were not observed in these instances, but the fungus was isolated from internal tissue.
Stem cells for all ages, yet hostage to aging.

In a tour de force, Rusty Gage and colleagues (1) showed that aging transcriptional changes in fibroblasts (FB) were reversed in induced pluripotent stem cells (iPSCs) derived from donors across the lifespan. Subsequently, when iPSCs were induced to form neurons by direct induction (iNS), the aging transcriptional signature was also absent. In contrast, when aging FBs were directly programmed to iNS by a similar protocol, they maintained an aging transcriptional signature. Remarkably, much of this signature was not the original signature of the FBs but a new age-associated signature more closely allied to neural related gene action. Thus, FB-derived iNS retained an “aging state” on direct cell programming, but not a hard wired, age-related transcriptional signature.
Validity and repeatability of goniometry in normal horses

Purpose: To assess validity and inter- and intra-tester reliability of equine goniometry and to establish values for carpal, metacarpophalangeal, tarsal, and metatarsophalangeal flexion and extension in horses. Subjects: Seventeen healthy equine subjects of varied breeds were used. Methods: Three investigators blindly and independently measured in triplicate the extension and flexion of carpal, metacarpophalangeal, tarsal, and metatarsophalangeal joints of 17 horses after sedation. Radiographs of these joints in flexion and extension were acquired while under sedation. Goniometric and radiographic measurements were compared statistically and were correlated. A Bland-Altman plot was constructed. Inter- and intra-tester repeatability of goniometry were evaluated by calculating intraclass correlation coefficients (ICC). Mean flexion and extension of carpal, metacarpophalangeal, tarsal, and metatarsophalangeal joints were calculated. Results: Goniometric and radiographic measurements did not differ statistically and were significantly correlated (correlation coefficients ranged from 0.59 - 0.89). The mean difference between goniometric and radiographic measurements was 0.4°. Triplicate measurements collected by the three raters did not differ significantly within raters (ICC ranging from 0.950 - 0.995) and between raters (ICC ranging from 0.942 - 0.989). Conclusion: Goniometry is a valid and repeatable tool for evaluation of the range of motion of carpal, metacarpophalangeal, tarsal, and metatarsophalangeal joints in standing, sedated healthy horses.
The Faerie Queene at Finnegans Wake

In James Joyce's Finnegans Wake, HCE and some of his tavern customers listen to a radio show about a Norwegian Captain, who tries, through his agent the Ship's Husband, to have a tailored suit made...
Inhibition of K(V) and K(Ca) channels antagonizes NO-induced relaxation in pulmonary artery.

Endogenous nitric oxide (NO) may contribute to the maintenance of normal pulmonary vasomotor tone, and inhaled NO is used to treat patients with pulmonary hypertension. Because pulmonary vascular tone is regulated by intracellular free Ca 2+ concentration and membrane potential, which are controlled by the K + channel activity in pulmonary artery (PA) smooth muscle cells, we sought to determine whether K + channels are involved in NO-induced relaxation and, if so, which types of K + channels are responsible. Authentic NO (∼0.3 μM) and sodium nitroprusside (SNP, 10 μM) both produced significant relaxation in isolated PA rings precontracted by increasing extracellular K + concentration. Further elevation of the K + concentration from 20 to 60 mM resulted in a significant increase in contraction but caused a marked decline in SNP-and NO-mediated PA relaxation. The dependence of SNP- and NO-induced relaxation on transmembrane K + gradient suggests that K + efflux through K + channels is involved in these effects. Furthermore, 4-aminopyridine (4-AP, 5-10 mM), which blocks voltage-gated K + channels (Kv), and charybdotoxin (200 nM), which blocks Ca 2+ -activated K + channels (K Ca ), both significantly inhibited NO- and SNP-induced PA relaxation. The ATP-sensitive K + channel blocker glibenclamide, however, had no effect on the relaxation response. The blocking of guanylate cyclase diminished, but did not abolish, the NO-induced relaxation, whereas 4-AP further decreased the NO-induced relaxant response in the presence of the guanylate cyclase inhibitor LY-83583. These data suggest that activation of both Kv channels and K Ca channels by guanosine 3',5'-cyclic monophosphate-dependent and -independent pathways is a mechanism, at least in part, by which NO induces PA relaxation.
Nonfatal Outcomes in the Primary Prevention of Atherosclerotic Cardiovascular Disease Is All-Cause Mortality Really All That Matters?

There is considerable debate in the literature regarding appropriate end points for studies of primary prevention of atherosclerotic cardiovascular disease (ASCVD), most notably with regard to statin therapy for hypercholesterolemia. Some authors have argued that large clinical trials of primary prevention interventions must demonstrate an overall mortality benefit1,2 or a combined overall mortality and serious morbidity benefit.3 Others feel that such a high bar would lead to the erroneous dismissal of several beneficial strategies that can substantially decrease incident ASCVD.2,4 Although several meta-analyses have now shown a modest mortality benefit of statins in primary prevention,5–8 the debate will undoubtedly be rekindled with the recent revision of the American College of Cardiology Foundation/American Heart Association (ACC/AHA) guidelines for the treatment of hypercholesterolemia.9 In this article, we advocate for the importance of nonfatal cardiovascular outcomes (nonfatal myocardial infarction [MI], nonfatal stroke, and peripheral arterial disease) in the assessment of ASCVD primary prevention strategies, illustrate this principle already in use in the management of hypertension, and advocate for the relevance of both nonfatal and fatal ASCVD events in the treatment of hypercholesterolemia in the primary prevention setting. The definition of benefit in the primary prevention of clinical ASCVD has recently been debated. Some authors suggest that an improvement in total mortality, of which cardiac death is only one part, is the only relevant benefit.1,2 Prasad and Vandross1 refer to examples of medications that improve surrogate end points but subsequently fail to improve overall survival, such as fibrates and niacin in certain patient populations. Importantly, no distinction is made between clinical, nonmortality end points (eg, nonfatal MI and stroke) and surrogate markers of clinical ASCVD risk (eg, low-density lipoprotein-cholesterol). This line of reasoning suggests that nonmortality end points are …
Deciphering Fedspeak: The Information Content of FOMC Meetings

We present a new approach to quantify the economic and policy content of Federal Reserve communications by dissecting the Federal Open Market Committee (FOMC) meeting minutes into distinct economic topics, and simultaneously extract the tone and uncertainty level of each topic. We use market reaction to objectively assess the relative informativeness of each topic, and we nd signicant
Comment on “The Relationship Between Friction and Film Thickness in EHD Point Contacts in the Presence of Longitudinal Roughness” by Guegan, Kadiric, Gabelli, & Spikes

Guegan and coworkers have addressed the important problem of friction of elastohydrodynamic contacts in the mixed regime. Any attempt at understanding friction in the mixed regime must address the friction in the full-film regime. To analyze fiction for the full film, they used a common, but unsupported, assumption that the friction curve is a rheological flow curve. The inconsistency can be demonstrated by integration over the contact with the assumed Eyring equation employing the known pressure dependence of the viscosity and also by a full numerical simulation which yields the same sinh friction curve without using the Eyring assumption.
Chapter 12 A Method for the Mass Culturing of Large Free-Living Amebas

Publisher Summary This chapter presents a method for mass culturing of large free-living amebas. The cultures are grown in Pyrex glass-baking dishes with inside dimensions of 33 × 21 × 4.5 cm; on the bottom of each dish is a plastic platform (30 × 20 cm) on small plastic feet of 2–3 mm high. This platform provides an added surface area on which the amebas can grow. Each dish normally contains ameba medium to a depth of 1–2 cm. The ameba medium is made up of 50 mg CaHPO4, 60 mg KC1, 40 mg MgSO4, and 1 liter glass-distilled H2O. Each culture dish normally contains 0.5–1.5 × 106 amebas. All estimations of ameba number are based on the finding that 4–5 × 105 living amebas pack into a volume of 1 ml when centrifuged for 1 minute at 200 g. The method described yields 20–25 × 106 amebas (or 40–50 ml packed cells) per week. Given sufficient resources, the system can be scaled up to provide considerably greater yields if desired.
Food Swamps Predict Obesity Rates Better Than Food Deserts in the United States

This paper investigates the effect of food environments, characterized as food swamps, on adult obesity rates. Food swamps have been described as areas with a high-density of establishments selling high-calorie fast food and junk food, relative to healthier food options. This study examines multiple ways of categorizing food environments as food swamps and food deserts, including alternate versions of the Retail Food Environment Index. We merged food outlet, sociodemographic and obesity data from the United States Department of Agriculture (USDA) Food Environment Atlas, the American Community Survey, and a commercial street reference dataset. We employed an instrumental variables (IV) strategy to correct for the endogeneity of food environments (i.e., that individuals self-select into neighborhoods and may consider food availability in their decision). Our results suggest that the presence of a food swamp is a stronger predictor of obesity rates than the absence of full-service grocery stores. We found, even after controlling for food desert effects, food swamps have a positive, statistically significant effect on adult obesity rates. All three food swamp measures indicated the same positive association, but reflected different magnitudes of the food swamp effect on rates of adult obesity (p values ranged from 0.00 to 0.16). Our adjustment for reverse causality, using an IV approach, revealed a stronger effect of food swamps than would have been obtained by naive ordinary least squares (OLS) estimates. The food swamp effect was stronger in counties with greater income inequality (p < 0.05) and where residents are less mobile (p < 0.01). Based on these findings, local government policies such as zoning laws simultaneously restricting access to unhealthy food outlets and incentivizing healthy food retailers to locate in underserved neighborhoods warrant consideration as strategies to increase health equity.
Parent-reported behavioral and emotional responses of children to disaster and parental psychopathology.

Child disaster mental health research has been largely limited by investigation of one disaster at a time and inconsistent methods across different studies. This study assessed 160 survivors of 3 d...
The Future of Public Opinion and Presidential Candidate Spouses

This chapter summarizes the comprehensive set of findings on US public opinion toward presidential candidate spouses in the context of the central theoretical frameworks advanced in the book: new traditionalism, the conditional nature of incumbency advantage, symbolic representation, partisanship and polarization, and the interdependent nature of public attitudes toward candidate spouses and the candidates themselves. It explores the implications of these empirical and theoretical findings for public opinion toward the current first lady Melania Trump as well as for how presidential candidate spouses will be viewed by the American public in future elections. The concluding chapter looks beyond the results of the 2016 presidential election by taking into consideration broader social and political trends and what they may mean for how the public views presidential candidate spouses. The chapter also offers suggestions for future scholarly research on the spouses of presidential campaigns.
Slow and steady wins the race? Future climate and land use change leaves the imperiled Blanding's turtle (Emydoidea blandingii) behind

Abstract Climate change is accompanied by shifts in species distributions, as portions of current ranges become less suitable. Maintaining or improving landscape connectivity to facilitate species movements is a primary approach to mitigate the effects of climate change on biodiversity. However, it is not clear how ongoing changes in land use and climate may affect the existing connectivity of landscapes. We evaluated shifts in habitat suitability and connectivity for the imperiled Blanding's turtle (Emydoidea blandingii) in Wisconsin using species distribution modeling in combination with different future scenarios of both land use change and climate change for the 2050s. We found that climate change had significant effects on both habitat suitability and connectivity, however, there was little difference in the magnitude of effects among different economic scenarios. Under both our low- and high-CO2 emissions scenarios, suitable habitat for the Blanding's turtle shifted northward. In the high-emissions scenario, almost no suitable habitat remained for Blanding's turtle in Wisconsin by the 2050s and there was up to a 100,000-fold increase in landscape resistance to turtle movement, suggesting the landscape essentially becomes impassable. Habitat loss and landscape resistance were exponentially greater in southern versus northern Wisconsin, indicating a strong trailing edge effect. Thus, populations at the southern edge of the range are likely to “fall behind” shifts in suitable habitat faster than northern populations. Given its limited dispersal capability, loss of suitable habitat may occur at a rate far faster than the Blanding's turtle can adjust to changing conditions via shifts in range.
The disconsolation of philosophy: May Sinclair, modernism, and disability

This article presents a new comparison of modernist literature and early twentieth-century philosophy as historically contemporaneous and mutually citational practices. Both offer a critique of the...
Leadership and team-based care.

When health professionals work collaboratively, scope of practice becomes more about defining roles and responsibilities among team members than about maintaining separate territories.
Determination of Calcium by Inductively Coupled Plasma-Atomic Emission Spectrometry, and Lead by Graphite Furnace Atomic Absorption Spectrometry, in Calcium Supplements after Microwave Dissolution or Dry-Ash Digestion: Method Trial

A 3-laboratory method trial was conducted to evaluate 2 sample digestion procedures and instrumental determination parameters for analysis of calcium and lead in Ca supplements. Calcium supplements were treated by dry-ash digestion or microwave dissolution prior to spectrometric analysis. In each case, Pb was determined by graphite furnace atomic absorption spectrometry and Ca by inductively coupled plasma-atomic emission spectrometry. Blind duplicates of 6 Ca supplement samples were analyzed after each sample treatment procedure. Matrix pairs contained dissimilar Pb levels to cover the analyte range encountered during method development. Calcium content of the Ca supplement samples also reflected the range seen during method development. Stock solutions of Ca and Pb were supplied to collaborators for preparation of quantitation standards to remove a variable external to the method. National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1486, bone meal, was included to assess method accuracy and recovery at NIST certificate Ca and Pb levels for this material (26.58 +/- 0.24% Ca and 1.335 +/- 0.014 micrograms Pb/g). Analyses of the NIST SRM yielded 25.9 +/- 1.1 and 27.2 +/- 2.3% Ca and 1.53 +/- 0.19 and 1.26 +/- 0.19 micrograms Pb/g for dry-ash and microwave procedures, respectively. Statistical analyses of data indicated acceptable repeatability and reproducibility for determination of Pb and Ca in various Ca supplements. With either sample preparation technique, the method is appropriate for determining Pb or Ca in Ca supplements.
THE SHAPES OF PLANETARY NEBULAE

In about 5 billion years our sun will mount a spectacu ar show of violent seismic activity that will eject nearly all of its gaseous layers into space. The event will take place on the eve of its decline, a last gasp before death. Dust and gas cast off by the dying star will be reshaped by a million-mile-per-hour wind and heated by a searing radiation from a hot white remnant lying at its center. Any survivor in the solar system will see the glowing gas as a colorful specter 500 times larger than Pluto's or? bit?a planetary nebula. Our sun's destiny is not unique; nearly 99 percent of all stars will share a similar finale. (Many of the rest will end their lives in a supernova explo? sion, a spectacular event in its own right.) Previous generations of stars have already met such a fate. Their ejected nebulae can be seen in modest telescopes, scattered here and there among the stars in our galaxy. By some estimates there may be more than 100,000 planetary nebulae in the Milky Way galaxy. More than 1,000 of these have been catalogued. The typical planetary nebula has a Hfetime of no more than 30,000 years or so?a brief moment in the 10-billion
Recent Results on Infrared Molecular Line Broadening and Shift Parameters

Infrared instruments designed to monitor atmospheric pollutants from space use observed radiances in specific spectral regions for retrievals of global distributions and atmospheric concentration profiles of the gases of interest, including CO, CH4, O3, HCN, NO2 and H2O. However, particularly for the troposphere, errors in the spectral line broadening and shift parameters and in the line shape models used in the “forward calculation” can contribute significantly to the total errors in retrievals of atmospheric gas concentration profiles. Line parameters in the HITRAN database for many of the gases mentioned above were significantly updated in the 2000 and 2004 editions. Nevertheless, uncertainties remain in some spectral regions, particularly in the understanding of line shapes, line mixing, and the temperature dependences of line broadening and shift parameters. The recent updates of broadening and shift parameters in the spectroscopic databases are reviewed, and new laboratory results are discussed.
College Students: The Rationale for Peer-to-Peer Video File Sharing

Peer-to-Peer networking is not a new concept within the academic world. Universities have been utilizing the Peer-to-Peer architecture for decades. Before the advent of the world-wide-web in the 1990s, the original ARPANET connected UCLA, Stanford Research Institute, UC Santa Barbara, and the University of Utah and allowed direct information sharing between researchers.1 Programs such as Bitnet allowed electronic communications between academics worldwide much earlier than e-mail and Instant Messenger. College campuses have also provided a robust breeding ground for content file sharing. Napster, one of the most popular Peer-to-Peer programs used to share music files was developed by Shawn Fanning while a freshman at Northeastern University and was introduced in May 1999. By end of that year, Napster’s membership had risen to millions – thanks to word of mouth advertisement at colleges and universities worldwide.
Proximity to unconventional shale gas infrastructure alters breeding bird abundance and distribution

Unconventional shale gas development is a rapidly expanding driver of forest loss and fragmentation in the central Appalachian region. We evaluated the relationship between breeding passerine abundances and distance from shale gas development at a long-term (2008–2017) study site in northern West Virginia, USA. We examined responses of 27 species within 3 habitat guilds: forest interior, early successional, and synanthropic. More than half of the species evaluated showed sensitivity to distance from unconventional shale gas infrastructure (e.g., well pads, access roads, pipelines). Five forest interior species occurred in greater abundances farther from shale gas development, whereas 3 forest interior gap specialists increased in abundance closer to shale gas. Early successional and synanthropic species, including the nest-parasitic Brown-headed Cowbird (Molothrus ater), generally occurred in greater abundances closer to shale gas infrastructure. We used interpolated distributions of 4 focal species to assess their spatial response to unconventional shale gas development over time. Our results indicate that breeding passerine distributions and community composition are changing with forest disturbance driven by unconventional shale gas energy development.
Abstract LB-274: Identification and characterization of LY3410738, a novel covalent inhibitor of cancer-associated mutant Isocitrate Dehydrogenase 1 (IDH1)

Somatic gain-of-function mutations in IDH1 have been identified in multiple tumor types including AML, glioma, cholangiocarcinoma and chondrosarcoma. The neo-enzymatic activity of mutant IDH1 results in accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), leading to a hyper-methylation phenotype, a block in cell differentiation, and tumor growth. Using a structure-based drug design approach, we have developed a highly potent covalent inhibitor of mutant IDH1. LY3410738 modifies a single cysteine (Cys269) in the allosteric binding pocket and rapidly inactivates the enzyme with a KI/Kinact = 84,257 M-1sec-1. The compound selectively inhibits the 2-HG in IDH1 mutant tumor cells without depleting the levels of a-ketoglutarate. Using patient-derived primary AML cells, we demonstrated that LY3410738 was more potent than AG120 in reversing the block in differentiation associated with IDH1 mutant activity. In vivo, LY3410738 displayed prolonged pharmacodynamic activity, depleting 2-HG levels in tumors at low circulating exposures and for an extended time after clearance of compound. Importantly, LY3410738 has the ability to cross the blood-brain barrier and can achieve concentrations in the brain that exceed those needed to engage the target. Consistent with this, LY3410738 effectively inhibits 2HG in orthotopic glioma models. Using patient-derived IDH1 mutant orthotopic AML models, we demonstrated that LY3410738 effectively inhibited 2-HG, induced differentiation, and cleared AML from mice. Collectively, LY3410738 represents the first covalent brain-penetrant mutant IDH1 inhibitor with potential for Best-in-Class activity. Citation Format: Nathan Brooks, Robin DeWalt, Serge Boulet, ZhaoHai Lu, Lisa Kays, Rachel cavitt, Sandra Gomez, John Strelow, Paul Milligan, Kenneth Roth, Renato Bauer, Stephen Antonysamy, Patric Hahn, Zoran Rankovic, Denis McCann, Gary Mo, Ramon Tiu, Timothy Burkholder, Sandaruwan Geeganage, Raymond Gilmour. Identification and characterization of LY3410738, a novel covalent inhibitor of cancer-associated mutant Isocitrate Dehydrogenase 1 (IDH1) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-274.
The Presentation of Donor Conception in Young Adult Fiction

Using a thematic analysis, this study examines the presentation of donor conception in 30 books of fiction written for young adults. Most of the donor-conceived characters in these books live in si...
Uncertainty Relations and Fluctuation Theorems for Bayes Nets.

Recent research has considered the stochastic thermodynamics of multiple interacting systems, representing the overall system as a Bayes net. I derive fluctuation theorems governing the entropy production (EP) of arbitrary sets of the systems in such a Bayes net. I also derive ``conditional'' fluctuation theorems, governing the distribution of EP in one set of systems conditioned on the EP of a different set of systems. I then derive thermodynamic uncertainty relations relating the EP of the overall system to the precisions of probability currents within the individual systems.
The Potential of Utilizing Mobile Cloud Computing in Mobile Devices

Nowadays, the rapid development and renaissance in mobile devices produces a fast-growing market. Also, the remarkable progress made in the mobile applications allows the mobile users to accomplish most of their electronic business through their mobile devices. However, there are some limitations in the mobile environment, which reduce the maximum benefits of using mobile devices. Therefore, mobile cloud computing was introduced as a potential enhancement for mobile services. It integrates the cloud computing into the mobile environment in order to overcome the limitations of mobile devices. This paper provides an overview about the advantages and challenges of mobile cloud computing. Also, it discusses some of the security risks are challenges.