cssi/SciSciGPT-SciSciNet huggingface dataset:
Parallel Evolution of Copy-Number Variation across Continents in Drosophila Melanogaster

Genetic differentiation across populations that is maintained in the presence of gene flow is a hallmark of spatially varying selection. In Drosophila melanogaster, the latitudinal clines across the eastern coasts of Australia and North America appear to be examples of this type of selection, with recent studies showing that a substantial portion of the D. melanogaster genome exhibits allele frequency differentiation with respect to latitude on both continents. As of yet there has been no genome-wide examination of differentiated copy-number variants (CNVs) in these geographic regions, despite their potential importance for phenotypic variation in Drosophila and other taxa. Here, we present an analysis of geographic variation in CNVs in D. melanogaster. We also present the first genomic analysis of geographic variation for copy-number variation in the sister species, D. simulans, in order to investigate patterns of parallel evolution in these close relatives. In D. melanogaster we find hundreds of CNVs, many of which show parallel patterns of geographic variation on both continents, lending support to the idea that they are influenced by spatially varying selection. These findings support the idea that polymorphic CNVs contribute to local adaptation in D. melanogaster In contrast, we find very few CNVs in D. simulans that are geographically differentiated in parallel on both continents, consistent with earlier work suggesting that clinal patterns are weaker in this species.
The diagnosis of jaundice

Abstract Although much study from a clinical and laboratory standpoint has been devoted recently to jaundice and hepatic diseases, the differential diagnosis is and should continue to be based essentially on clinical data. The presence or absence of pain and its character when present is the most important single fact in such differentiation. Laboratory procedures have given new impetus to study of these cases, have changed methods of practice to some extent, and have introduced new conceptions of the mechanism of jaundice. Thus, duodenal drainage to determine the amount of bile entering the intestine is used more frequently because they give more definite information than examination of the feces and urine. The reaction of the serum to the van den Bergh test, and the height and contour of the curve of bilirubin give a much more accurate idea of the type of the icterus, its severity, and its fluctuations than does observation of the color of the skin or examination of the urine and feces. We feel that the van den Bergh test is one of the most useful of the various tests that have been advocated in the study of jaundice. The coagulation time of the blood is also a valuable procedure, but must also be coupled with clinical observation of the patient. The conception has developed that all jaundice is not obstructive in cause, but that jaundice may also be of hepatic or hemolytic origin. Although the majority of cases are probably distinctly of one type, yet in practice cases are seen in which the icterus originates in more than one way. Thus, the cases of hemolytic jaundice may have an associated hepatic or obstructive element or the cases of obstructive jaundice may have an associated hepatic element. At present there is not any specific test for distinguishing between hepatic jaundice and obstructive jaundice if the obstruction is partial. The need for such a test is especially great when obstruction has developed without the accompaniment of pain. The mechanism of the icterus in hepatic jaundice is not understood. The classification of the group is unsatisfactory. Although some forms of jaundice, such as that due to chloroform, have largely disappeared, other forms have appeared since the introduction of the arsphenamine and cinchophen drugs. Precautions in the use of these drugs are constantly necessary.
The Religion of Democracy in Early Twentieth-Century America

When President Woodrow Wilson asked for a declaration of war against Germany on 2 April 1917, he uttered his famous warning to Congress that "the world must be made safe for democracy."1 Two years later, when the secretary of the North ern Baptist Convention, Frederick Alfred Agar, published his book, Democracy and the Church, he cited the less famous but in some circles apparently commonplace corollary that "democracy must be made safe for the world."2 The safeness, as well as the meaning and future, of democracy had come into question between the Wilson and Agar statements specifically because of the Bolshevik Revolution in Russia and its claim to represent the new forces of economic democracy. Even within its more traditional political sphere, however, democracy had been under scrutiny for almost a generation, and especially since the nation's military suppression of the democratic spirit in the Philippines following the Spanish-American War.3 Some American religion ists responded to the fate of the Filipino insurrection by rethink ing Christianity's doctrines of the brotherhood of all persons and the Fatherhood of God. The result was a variety of the "religion of democracy" that was a prophetic faith in the spiritual oneness of Christianity and democracy, based on the democratic theology of Christianity and concerned primarily with the survival of Christianity in troubled modern democracies.4
A Model of Order-Selectivity Based on Dynamic Changes in the Balance of Excitation and Inhibition produced by Short-term synaptic Plasticity

Determining the order of sensory events separated by a few hundred milliseconds is critical to many forms of sensory processing, including vocalization and speech discrimination. Although many expe...
Exploring the Arctic’s “other economies”: knowledge, creativity and the new frontier

AbstractThe stylised notion of the Arctic’s economy as solely based on three “pillars”: resources, public and traditional sectors, is no longer nuanced enough to accommodate the growing role of Arctic’s “other” (non-pillar) economies prompted by the worldwide shift to tertiary and quaternary sectors. The goal of this paper is to introduce and showcase the Arctic’s “other economies” and offer a patchwork of cases that illuminate various aspects of “other” economies. These studies include an investigation of the Arctic’s knowledge economy at the circumpolar and regional scales, a study of cultural economy and an inquiry into the relationships between “other” and “pillar” Arctic sectors. The paper concludes that although the volume of knowledge production in the Arctic is still comparatively small and economic engagement of local creativity is relatively weak, Arctic economic systems are evolving to increasingly incorporate these sectors. The Arctic knowledge economy is characterised by the key role of indiv...
A Simple Method for Estimation of Dielectric Constants and Polarizabilities of Nonpolar and Slightly Polar Hydrocarbons

Many of the liquids that are used as electrical insulators are nonpolar or slightly polar petroleum-derived hydrocarbons, such as the ones used for cable and/or transformer oils. In this work, semi-empirical expressions with no adjustable parameters for the dielectric constant and the polarizability of nonpolar and slightly polar hydrocarbons and their mixtures are proposed and validated. The expressions that were derived using the Vargas–Chapman One-Third rule require the mass density and the molecular weight of the substance of interest. The equations were successfully tested for various hydrocarbons and polymers with dipole moments <0.23 and densities from 500 to 1200 kg $$\cdot $$ $$\hbox {m}^{-3}$$ . The predictions are in good agreement with the experimental data in a wide range of temperatures and pressures. The proposed expressions eliminate the need of extensive experimental data and require less input parameters compared to existing correlations.
Ocean Current Energy Conversion

Ocean currents in tidal flows and at the western boundaries of the ocean basins, as well as currents in rivers, can have as much potential for power production as the wind. With increased interest in sources of renewable energy, realizing this potential has undergone a renaissance in recent years. This chapter provides an introduction to ocean current energy conversion by emphasizing the contrasts between winds and currents and discussing some of the unique challenges associated with this untapped renewable energy source.
No Laughing Matter: Women's Verbal and Nonverbal Reactions to Sexist Humor

Publisher Summary Humor may not always be a means of evoking amusement and it is a known fact that hostility that cannot be expressed directly can be safely and subtly expressed by humor. As seen in studies performed by Cantor and Zillman, women are often the center of disparaging jokes, and this is classified as sexist humor. At times, sexist jokes meaning no harm can also be perceived as a means of transmitting discriminatory behavior. This chapter illustrates the responses of women to this kind of sexist humor. Sexism is now being newly looked upon and analyzed, as the current gender attitudes are seen to be more complex in nature when compared to previous results evaluated with the help of uni-dimensional measures. Ambivalent Sexism Inventory (ASI), devised by Glick and Fiske, analyzes both hostile and benevolent sexism, and help in understanding the reception of sexist jokes by women. Verbal and nonverbal responses of women to sexist humor have been further studied with the help of facial action coding system (FAC). At times, sexist humor can cause serious damage and it is important to know the responses and reactions of women to this behavior.
Exercise training for older adults with limitations in physical function

This study aimed to evaluate the effects of an 8-week supervised exercise program on physiological measurements during treadmill walking, muscle strength, functional performance, and health status in older adults limited in physical function. Twenty-four participants were randomly assigned to an exercise group (EG, N = 13) or a control group (CG, N = 11), and were evaluated before and after the exercise program (EG) or 8-week period (CG). Evaluations included a progressive treadmill lest, strength testing, the Physical Performance Test (PPT), and the SF-36 Health Survey. The exercise program consisted of 3 sessions per week of brisk walking and strengthening exercises. The EG demonstrated increases in cardiorespiratory fitness and increases in treadmill walking time. The EG also demonstrated increases in force production in 3 of the 6 muscle groups that were tested. Both the EG and CG demonstrated improvements in PPT scores and in 2 health concepts on the SF-36 Health Survey.
Civil-Military Relations in Communist Systems: Western Models Revisited

Civil-military relations in Communist systems are crucial for our understanding of the military’s role and function in such political environments. Examining military establishments in democratic polities, while paying little attention to the existing political structure might well be a fruitful undertaking. The organizational structures and basic functions of Communist armed forces, however, cannot be understood without analyzing their relationships to their respective polities. Although all military establishments have inherently strong ties to their polities, these links are far stronger and more varied in Communist systems.
Influence of strain on the electronic properties of epitaxial V2O3 thin films

Abstract Thin films of V2O3 with thickness of 20–450 nm were grown on (0001) oriented sapphire substrates by reactive electron-beam evaporation. Low-energy electron diffraction, X-ray diffraction and atomic force microscopy studies show highly oriented grains with a lateral size of 50 to 800 nm, dependent on substrate temperature and deposition rate. The films were characterized by transmission measurements in the optical and infrared region, electrical resistance and Hall effect measurements. A variation of the growth parameters yields three different “types” of V2O3 films characterized by (i) a metal–insulator transition similar to bulk material (type 1), (ii) an insulator–metal followed by a metal–insulator transition (type 2) below room temperature and (iii) an insulator–insulator transition (type 3). The different types of V2O3 films mimic the behavior of chromium doped V2O3 with increasing Cr concentration. The c lattice parameter correlates with the electronic properties of the respective films, suggesting that this effect might be explained by a varying degree of strain in the films. © 1997 Elsevier Science S.A.
Surveying Issues That Arise in Women's Prisons: A Content Critique of Orange Is the New Black

The character Piper Chapman is presented in the Netflix original series, Orange Is the New Black (OITNB). Piper's story opens the door to the female correctional facility. With the mass incarceration of non-violent, drug offending females comes the need for gender-specific assessment, programming, and reentry efforts. It is the goal of this essay to briefly review several issues observed in OITNB (gender, victimization, sexuality, mental health/addiction, and race) and to raise awareness on additional issues related to women and crime. The essay will also provide a discussion on female relationships to include both outside loved ones as well as newfound friends within the facility and the accompanied policy implications. Research supports the idea that contact with prosocial loved ones reduces distress and recidivism. Policy implications suggest a need for more open visitation, assistance with welfare agencies, collaboration for reentry, and overall gender-specific programming needs for female offenders.
September 11 and American Law

Fads and fashions affect theories of American law of course, but September 11 resulted in an eclipse of dominant ways of 'doing' law - and of the powers of courts and the Congress - an eclipse of uncertain length as of this writing. I document the eclipse of a neconservative law and economics and (chiefly as Laura Kalman uses the term) a legal liberalism. Tacitly adopting an 'alien' jurisprudence from Machiavelli, Carl Schmitt, and Hans Vaihinger, the Executive Branch SEEMS bent on using a "War on Terror" to transform our vulnerable society and economy (a civil libertarian and modestly welfare state) into a "warfare state," especially through expansions in the governance by special interests that is opposed by economists and legal liberals alike. Contrary to the views of some legal academics, American life and law are clearly at a turning point. I close by offering some solutions to the problems I raise.
Striving beyond Epistemic Authority: Results Dissemination in Smallholder Irrigation Farming Research

Epistemic authority is the institutional measure of trustworthiness and reliability of our work. Can we really claim, though, that our research is reliable if we do not create spaces for sharing potential societal benefits with the communities we investigate and with which we work? Against this backdrop, I aim to examine the practice of results dissemination and its potential benefits for researched communities. This reflection is produced through the analysis of a ten-day itinerant dissemination workshop that took place in January 2015 between Kenya and Tanzania. Results were presented to local participants through booklets in English, Swahili, and Marakwet. Although societal impact is a long-term process, I discuss some benefits that emerged during the ten-day workshop: seeds exchange, learning of agricultural practices, debating women's exclusion from irrigation, the use of the booklet with results in school, and the transliteration of the spoken language of Marakwet. By giving researchers and particip...
Analyzing the metabolic capabilities of a Vibrio parahaemolyticus strain that causes Early Mortality Syndrome in shrimp

Abstract Shrimp disease results in significant annual economic loss to the global aquaculture industry. Since 2009, the primary causative agent of shrimp disease has been Vibrio parahaemolyticus (VP) strains that cause Early Mortality Syndrome (EMS) or acute hepatopancreatic necrosis disease (AHPND). EMS strains have acquired a plasmid via horizontal gene transfer that encodes an insect toxin, which is responsible for the rapid death of infected shrimp. Based on previous experiments, it was hypothesized that an EMS strain of VP has unique growth properties compared to other VP strains, which may give it an interspecific competitive advantage in the environment. Accordingly, three strains of VP underwent testing; EMS 13-028/A3 that causes EMS disease in shrimp, RIMD2210633 that is a human clinical isolate, and LM5312 that is an environmental isolate. The ability of these three different strains of VP to grow on 71 different carbon sources/substrates was measured using Biolog GEN III MicroPlates. The EMS strain was able to utilize a variety of nutrient sources (23 out of 71) more efficiently than the other two strains as ascertained by significantly greater growth. A comparative bioinformatics analysis of the EMS genome identified a unique set of genes associated with fucose metabolism. This study demonstrates that Biolog plates can be used to ascertain distinctive metabolic properties of pathogenic bacterial strains such as VP EMS that may help guide development of new disease mitigation strategies for production of shrimp in aquaculture environments.
The second epidemiologic transition on the brink: What we can learn from the island of Newfoundland during the early 20th century.

Objectives We aim to understand how the second epidemiologic transition unfolded on the island of Newfoundland during the early 20th century. The focus is on changes in predominant causes of mortality throughout this period, urban and rural differences, and comparisons with other Western nations. We explore factors driving these patterns including the economy, nutrition, sanitation, and access to healthcare and discuss their relevance to understanding epidemiologic transitions in other developing regions. Methods We examined official provincial death records (n = 65,394) and census materials from 1900 to 1939 for three rural districts (Burgeo-La Poile, Bonavista, and Twillingate) and the large city of St. John's. Life expectancies, infant mortality rates, survival curves, and proportionate mortality from communicable and non-communicable diseases (NCDs) were calculated. RESULTS In all districts, old age mortality increased while infant and childhood mortality decreased, with corresponding increases in life expectancy. Proportionate mortality from communicable causes decreased while deaths from NCDs increased. These changes occurred earlier in urban St. John's than in outlying districts, suggesting rural–urban differences played a significant role in Newfoundland's second epidemiologic transition. However, the transition was significantly delayed relative to other Western nations. CONCLUSIONS We suggest that observed mortality patterns were the result of complex interactions between the poor economy, malnutrition, high prevalence of tuberculosis, and limited health and social services. These factors contribute to the delayed onset of the second epidemiologic transition in Newfoundland relative to other Western nations and the earlier onset in St. John's than in rural areas.
Cutaneous Microbial Community Variation across Populations of Eastern Hellbenders (Cryptobranchus alleganiensis alleganiensis).

Multicellular hosts maintain complex associations with microbial communities. While microbial communities often serve important functional roles for their hosts, our understanding of the local and regional processes that structure these communities remains limited. Metacommunity analyses provide a promising tool for investigating mechanisms shaping microbiome heterogeneity, which is essential for predicting functional variation between hosts. Using a metacommunity framework, we examined heterogeneity in the skin microbiome of the eastern hellbender (Cryptobranchus alleganiensis alleganiensis). Hellbenders are broadly distributed throughout river systems in the eastern United States, but are present in specific environment locations throughout their range. The large range of the species and history of population fragmentation suggest that local and regional processes contribute to the distribution of cutaneous symbiont diversity. Therefore, we characterized the skin and environmental bacterial communities at eight rivers throughout the range of the species. We observed variation among hellbender populations in skin microbial community diversity and proportion of shared operational taxonomic units (OTUs) between animal and river water communities. Among populations sampled, we noted significant clumped OTU turnover (i.e., Clementsian structure) resulting in unique cutaneous communities. In addition, we observed a significant positive correlation between skin community divergence and hellbender population genetic divergence. Host-population skin community dissimilarity did not correlate strongly with distance between sampling locations, indicating a weak spatial effect on the distribution of symbionts. These results suggest that species sorting mechanisms (i.e., local processes) structure local skin microbial communities in hellbenders. The variation in skin community composition observed among host populations foreshadows a similar pattern in important functional characteristics (e.g, resistance to dysbiosis). Future work should focus on investigating forces shaping microbiome structure in eastern hellbenders, examining functional variation among populations, and evaluating effectiveness of microbiome management recommendations.
Applications of Inferred Origins, Destinations, and Interchanges in Bus Service Planning

A growing number of researchers and transit agencies are using fare card and vehicle location data to infer passengers’ origins, destinations, and transfers. A number of researchers have suggested that these new data sets provide valuable information for transit network design, but few concrete applications have been developed to address bus network design and service planning problems. This paper proposes new service planning procedures to aggregate these automated data to examine travel patterns to specific locations of interest to propose needed improvements. The data from existing passengers’ trips are then analyzed to assess the benefits of the proposed service changes. In particular, the number of existing passengers who would likely experience shorter travel times with the service changes is calculated according to the geometry of how a proposed new or extended route intersects with the existing transit network. The results of this analysis provide planners with better information than is currently...
Bulk permittivity of a composite with coated spheroidal filler particles

The bulk complex permittivity of a composite material is calculated analytically. The filler particles are spheroidal and may be coated with a surface layer whose intrinsic material properties differ from those of the core. Making the assumption that the filler particles are arranged on a simple-cubic lattice, interactions between the particles are accounted for by treating each particle mathematically as a multipole source. The coefficients of the multipole expansion, suitably-truncated, are determined by solving a matrix equation obtained by matching with the general solution of Laplace's equation in the interstitial domain, expressed in terms of an expansion in spheroidal harmonics. Matching is carried out at the surface of a representative particle according to electromagnetic continuity conditions. Example calculations demonstrate the effect of varying filler volume fraction, intrinsic material properties, layer thickness, particle shape and frequency. Results are shown to agree with independent work, where available.
Geomorphologist's Guide to Participating in River Rehabilitation

There is a strong scientific consensus that river corridors are badly damaged by societal impacts, costing the United States alone more than $76 billion yr-1 and harming many species beyond assignment of any dollar value. In response to this problem, society has called upon governments, scientists, and private consultants to rehabilitate rivers. A scientific consensus has emerged that process-based rehabilitation within a watershed-scale context is highly important for a successful outcome. Unfortunately, the science underlying linked abiotic-biotic processes in rivers is still rudimentary, relative to the complexity of the ecosystem to design and build process-based solutions with the same success evident in the practice of medicine or the manufacture of buildings and other civil structures. Many existing practices have been vetted and found by scientific experts to be largely ineffective. Multiple paradigms for rehabilitation based on different combinations of scientific complexity, universality, and comprehensivity are diverging and splintering the technical community. Lacking a consensus among academic scientists and private practitioners, it is too soon to establish professional standards or regulatory requirements. Within this context, geomorphologists have a key role in getting involved in all phases of river rehabilitation and bringing their perspective and capabilities to bear on the grand challenge of preventing environmental collapse. © 2013 Elsevier Inc. All rights reserved.
The Role of Diluent in Oily Waste Water Treatment in Bed Coalescers

Abstract Periodic or continuous kerosene injection into an oily waste water stream has been shown to cause liberation of a coalescer bed from accumulated oil and suspended matter. Thus the lifetime of the bed was extended several times with respect to an unregenerated one, without a decrease of coalescence efficiency.
Characterizing colonic detections in CT colonography using curvature-based feature descriptor and bag-of-words model

We present a method based on the content-based image retrieval (CBIR) paradigm to enhance the performance of computer aided detection (CAD) in computed tomographic colonography (CTC). The method explores curvature-based feature descriptors in conjunction with bag-of-words (BoW) models to characterize colonic detections. The diffusion distance is adopted to improve feature matching and clustering. Word selection is also applied to remove non-informative words. A representative database is constructed to categorize different types of detections. Query detections are compared with the database for classification. We evaluated the performance of the system by using digital phantoms of common structures in the colon as well as real CAD detections. The results demonstrated the potential of our technique for distinguishing common structures within the colon as well as for classifying true and false-positive CAD detections.
The ‘Virtuous Circle’ Argument, Political Judgement, and Citizens’ Political Resistance

Empirical scholars describe a ‘virtuous circle’ (VC) wherein effective governance, empirical legitimacy, and citizens’ obedience are mutually reinforcing. This essay offers a normative perspective ...
Predictive model algorithms identifying early and advanced stage ER+/HER2− breast cancer in claims data

Purpose Claims databases offer large populations for research, but lack clinical details. We aimed to develop predictive models to identify estrogen receptor positive (ER+) and human epidermal growth factor negative (HER2-) early breast cancer (ESBC) and advanced stage breast cancer (ASBC) in a claims database. Methods Female breast cancer cases in Anthem's Cancer Care Quality Program served as the gold standard validation sample. Predictive models were developed from clinical knowledge and empirically from claims data using logistic and lasso regression. Model performance was assessed by classification rates and c-statistics. Models were applied to the HealthCore Integrated Research Database (claims) to identify cohorts of women with ER+/HER2- ESBC and ASBC. Results The validation sample included 3184 women with ER+/HER2- ESBC and 1436 with ER+/HER2- ASBC. Predictive models for ER+/HER2- ESBC and ASBC included 25 and 20 factors, respectively. Models had robust discrimination in identifying cases (c-stat = 0.92 for ESBC and 0.95 for ASBC). Compared with a traditional a priori algorithm developed with clinical insight alone, the ER+/HER2- ASBC-predictive model had better positive predictive value (PPV) (0.91, 95% CI, 0.90-0.93, vs 0.69, 95% CI, 0.66-0.73) and sensitivity (0.54 vs 0.35). Models were applied to the claims database to identify cohorts of 33 001 and 3198 women with ER+/HER2- ESBC and ASBC. Conclusion We conducted a validation study and developed predictive models to identify in a claims database cohorts of women with ER+/HER2- ESBC and ASBC. The models identified large cohorts in the claims data that can be used to characterize indications in the evaluation of targeted therapies.
Poliovirus vaccine formulations

Most of the early trials of Sabin-derived, live attenuated oral poliovirus vaccine (OPV) involved sequential administration of a single dose of each poliovirus type in monovalent form. Replication of each Sabin strain in the gastrointestinal tract was usually demonstrated in 90–100% of seronegative subjects at dosage levels of ≥ 105 TCID50. However, when the same dosage of each Sabin type were mixed together and administered as a trivalent preparation (TOPV), intestinal excretion and subsequent antibody production were consistently lower for types 1 (50%–70%) and 3 (55%–75%), with no apparent effect on type 2 (96%–100%). In an effect to compensate for these deficiencies, which were largely attributed to interference from type 2, “balanced” formulations were developed and tested in Canada in the early 1960s in which higher relative potencies of types 1 (106 TCID50) and 3 (105.5 [300000] TCID50) were associated with coresponding increases in seroconversion rates. Limited studies in developing countries have revealed similar findings, although antibody responses to types 1 and 3 after three doses of the currently recommended formulation of TOPV have often remained suboptional. In view of the limited resources currently available for the poliomyelitis eradication initiative and the need to maximize the efficiency of vaccine delivery by achieving higher rates of seroconversion early in life, the development of more immunogenic formulations of TOPV remains a high priority.
Resveratrol (RES) and its antagonist, sirtinol suppress human cytomegalovirus (hCMV) replication and hCMV induced transcription of proinflammatory cytokines and chemokines in THP-1 derived macrophages

Background Mounting evidence suggests significant contribution of chronic hCMV infection to T-cell immunosenenscence and chronic inflammation in old adults. THP-1, a human monocytic cell line and its derived macrophages serve as a useful cell culture model to study hCMV infection and its biology. Novel anti-CMV agents are needed as current anti-CMV treatment is limited in efficacy with significant side effects. We and others observed that Resveratrol (RES) and sirtinol, suppressed CMV replication in human fibroblasts. Here we report their inhibition on hCMV replication and hCMV induced expression of IL-6, IP-10, MCP-1 and TNF-a in THP-1 derived macrophages. Methods THP-1 cells were differentiated into macrophages after incubation with PMA (50 ng/ml) in RPMI 1640 with 10%FBS for 24 hrs. RES or sirtinol was added 2 h followed by hCMV (Towne strain) inoculation at multiplicity of infection of MOI 2 for 24 hrs. Cells were then cultured in hCMV-free medium for indicated times. qPCR and RT-PCR were performed to evaluate hCMV replication and transcription of IL-6, IP-10, MCP-1 and TNF-a, respectively. Results Both RES and sirtinol suppressed hCMV replication. They also suppressed hCMV induced transcription of proinflammatory mediators except for TNF-a. Conclusions and discussion These findings indicate potent inhibition of hCMV infection and hCMV induced transcription of proinflammatory mediators by RES and sirtinol in THP-1 derived macrophages. While being non-permissive, monocytes are important reservoir for chronic or latent CMV infection. Further investigation into the role and mechanisms of RES, sirtinol and other agents in control of chronic CMV infection and its adverse impact is indicated.
DLL3: an emerging target in small cell lung cancer

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with extensive-stage disease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors but minimally expressed in normal tissues. It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the antibody-drug conjugate rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the chimeric antigen receptor T cell therapy AMG 119.
m6A-binding YTHDF proteins promote stress granule formation by modulating phase separation of stress granule proteins

Abstract Diverse RNAs and RNA-binding proteins form phase-separated, membraneless granules in cells under stress conditions. However, the role of the prevalent mRNA methylation, m6A, and its binding proteins in stress granule (SG) assembly remain unclear. Here, we show that m6A-modified mRNAs are enriched in SGs, and that m6A-binding YTHDF proteins are critical for SG formation. Depletion of YTHDF1/3 inhibits SG formation and recruitment of m6A-modified mRNAs to SGs. Both the N-terminal intrinsically disordered region and the C-terminal m6A-binding YTH domain of YTHDF proteins are crucial for SG formation. Super-resolution imaging further reveals that YTHDF proteins are in a super-saturated state, forming clusters that reside in the periphery of and at the junctions between SG core clusters, and promote SG phase separation by reducing the activation energy barrier and critical size for condensate formation. Our results reveal a new function and mechanistic insights of the m6A-binding YTHDF proteins in regulating phase separation.
North Carolina community pharmacists' attitudes about suicide and willingness to conduct suicidal ideation assessment: A cross-sectional survey study.

Abstract Background Suicide is a major and growing public health problem. Pharmacists are one of the most accessible members of the health care team. Due to their unique place in the health care system, pharmacists may be an ideal resource for monitoring patients at risk of suicide. The objectives of this study were to: (1) investigate community pharmacists’ attitudes toward suicide; (2) identify pharmacist-reported barriers to suicidal ideation assessment; and (3) evaluate facilitators and barriers to pharmacists conducting suicidal ideation assessment. Methods An anonymous questionnaire was distributed to North Carolina (NC) community pharmacists. Measures included contact with suicide, perceived role in suicidal ideation assessment, Attitudes Towards Suicide (ATTS), and barriers in suicidal ideation assessment. Multivariable logistic regression was used to analyze the data. Results There were usable and complete data for 225 participants (3.52% response rate). The median ATTS score was 70 (IQR = 7). Community pharmacists were significantly more likely to perform a suicidal ideation assessment at least sometimes when (s)he reported a lower number of barriers (OR = 0.70, 99.5% CI = 0.51–0.98) and when (s)he agreed or strongly agreed that they knew how to help someone who was suicidal (OR = 6.63, 99.5% CI = 1.74, 25.23). The most common barrier to suicidal ideation assessment was lack of education in mental health screening (n = 176). Conclusions Suicide prevention education programs for pharmacists may need to address reducing barriers, increasing knowledge about suicide, and improving self-efficacy. Targeting these areas may lead more pharmacists conducting these assessments.
Itinerario de José María Arguedas. Migración, peregrinaje y lenguaje en El zorro de arriba y el zorro de abajo

Este articulo explora la novela de Arguedas desde dos aspectos que se interconectan. El primero es la representacion de un mundo sujeto a una aceleracion en su dinamica social y economica, donde los elementos mas visibles son la migracion y la instauracion de un capitalismo primario. Este mundo tiene su concrecion geografica e historica en el puerto peruano de Chimbote que, en su repentina prosperidad, atrae a miles de inmigrantes y se convierte en una suerte de laboratorio humano. El segundo aspecto es el de la autorrepresentacion del escritor en su relacion con los otros, en el proceso de escritura y en su progreso hacia el suicidio. En este escenario emerge un dialogismo cultural solidario; tal dialogismo es posibilitado por una creciente creatividad cultural que transforma los espacios y los agentes que intervienen en el, y por un lenguaje sagrado y sincretico que recupera para lo humano un espacio revertido (el del mercado), otorga a la palabra un don reparador e implica el reconocimiento del valor del otro.
Black-Box Strategies and Equilibrium for Games with Cumulative Prospect Theoretic Players.

The betweenness property of preference relations states that a probability mixture of two lotteries should lie between them in preference. It is a weakened form of the independence property and hence satisfied in expected utility theory (EUT). Experimental violations of betweenness are well-documented and several preference theories, notably cumulative prospect theory (CPT), do not satisfy betweenness. We prove that CPT preferences satisfy betweenness if and only if they conform with EUT preferences. In game theory, lack of betweenness in the players' preference relations makes it essential to distinguish between the two interpretations of a mixed action by a player - conscious randomizations by the player and the uncertainty in the beliefs of the opponents. We elaborate on this distinction and study its implication for the definition of Nash equilibrium. This results in four different notions of equilibrium, with pure and mixed action Nash equilibrium being two of them. We dub the other two pure and mixed black-box strategy Nash equilibrium respectively. We resolve the issue of existence of such equilibria and examine how these different notions of equilibrium compare with each other.
Chapter 7 – Zebrafish

The zebrafish shares basic nervous system organization with other vertebrates; many neural circuits and cell types relevant to human disease are conserved in the zebrafish central nervous system. In addition, many genes implicated in human neurological disorders have highly conserved orthologues in the zebrafish genome, suggesting that the biochemical events underlying pathogenesis could be recapitulated in the zebrafish nervous system. Zebrafish have been used to study vertebrate development for many years, and the recent generation of zebrafish models of human neurological disease has exploited many of the resulting methods for genetic manipulation, gene expression analysis, and imaging. Potentially, zebrafish models could be exploited for studies that could not be carried out practicably in other vertebrates. Larval zebrafish can be housed in 96-well plates, where they can be exposed to small molecule libraries for drug discovery. Furthermore, genetic screens can be used to isolate phenotypic modifiers. Finally, zebrafish are amenable to in vivo imaging modalities, genetic and environmental manipulations, electrophysiological recordings, and neurobehavioral studies, potentially allowing key mechanistic insights to be gained rapidly by traditional hypothesis-driven experiments. This chapter discusses the relevance of the zebrafish model to human motor disorders and reviews the major techniques for genetic manipulation, chemical exposures, and neurobehavioral evaluation used to generate and analyze zebrafish models of movement disorders.
Contextual Influences on Managers’ Restorative vs. Punitive Responses to Workplace Wrongdoing

A growing stream of management literature examines how reparative or restorative responses can be integrated with traditional punishment in responding to employee wrongdoing (e.g., Goodstein & Aqui...
Disorders of Bilirubin Metabolism

Bilirubin, a by-product of hemoglobin degradation, can accumulate in the body due to a number of different conditions including genetic disorders. The degree and type of hyperbilirubinemia differ depending on the genetic mutation. This chapter will discuss the normal process of bilirubin metabolism as well as the various disorders of bilirubin metabolism that cause hyperbilirubinemia in children.
The significant interaction between age and diabetes mellitus for colorectal cancer: Evidence from NHANES data 1999-2016

Abstract Background Diabetes mellitus has been associated with elevated risk of colorectal cancer (CRC), although interaction between age and DM is unclear. We examined the relationship among DM, CRC and age. Methods 22,580 subjects aged ≥18 years were identified from the National Health and Nutrition Examination Survey (NHANES) database collected between 1999–2016. To account for the complex, stratified, multistage probability sampling design in NHANES, SASv9.4 Procedure Survey Methodology was applied. Univariate analysis compared individual baseline characteristics between subjects with and without DM. Multivariate logistic regression model assessed association between DM and CRC, in which the model included factors with p Results Univariate analysis showed significant differences in age (p 65 were not at increased risk for CRC (OR = 0.83, 95%CI = (0.43–1.59); p = 0.5665) compared to those without DM. Conclusions Age, DM, and interaction between age and DM are risk factors for CRC. Individuals with DM aged 18–65 years have a higher CRC risk.
Exercise 13: Immunoblotting (Western Blotting)

Western blotting (also known as immunoblotting), is a highly sensitive, solid-phase assay that is performed routinely in research and clinical laboratories. It is routinely performed to detect the presence of specific antibodies to an antigen or to identify a specific antigen in a complex mixture of proteins. For example, a specific viral, bacterial or parasite antigen can be identified by its reactivity with specific antibodies from an individual patient's serum. In general, a specific antibody is used to identify a specific cognate antigen from a heterogeneous mixture of proteins. The protein identified is in a denatured, linear conformation on transferred to nitrocellulose paper or nylon membrane from a replica SDS-PAGE gel. Polyclonal, monospecific polyclonal or monoclonal antibodies (primary antibodies) are employed in western blotting assays, and incubated with the transferred proteins on nitrocellulose paper following blocking of non-reactive sites on the paper by albumin, gelatin or milk proteins in the presence of Tween to reduce nonspecific binding. The primary antibodies are detected by species-specific secondary antibody conjugated to an enzyme such as alkaline phosphatase, horseradish peroxidase or biotin-labeled antibodies can be detected by the specific interaction of enzyme conjugated streptavidin. Cleavage of an enzyme substrate, results in the development of an insoluble colored product that precipitates on the protein bands, making the specific reactive protein bands visible against the white background of the nitrocellulose paper. The secondary antibodies may also be labeled with a radioactive substrate such as 1251 iodine and the antigen–antibody complexes detected on X-ray film by autoradiography. For safety reasons, detection is now commonly detected by colorimetry, by chemiluminescence or by fluorescence. Levels of antibody reactivity and the intensity of protein bands detected can be quantitated when chemiluminescenc or fluorescence is used for detection.
Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization

The global pandemic of Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 has become a severe global health problem because of its rapid spread(1). Both angiotensin-converting enzyme 2 and neuropilin 1 provide initial viral binding sites for SARS-CoV-2 (2, 3). Here, we show that three cysteine residues located in a1/a2 and b1 domains of neuropilin 1 are necessary for SARS-CoV-2 spike protein internalization in human cells. Mutating cysteines C82, C104 and C147 altered neuropilin 1 stability and binding ability as well as cellular internalization and lysosomal translocation of the spike protein. This resulted in up to 4 times reduction in spike protein load in cells for the original, alpha and delta SARS-CoV-2 variants even in the presence of the endogenous angiotensin-converting enzyme 2 receptor. Transcriptome analysis of cells transfected with mutated NRP1 revealed significantly reduced expression of genes involved in viral infection and replication, including eight members of the ribosomal protein L, ten members of ribosomal protein S and five members of the proteasome {beta} subunit family proteins. We also observed higher expression of genes involved in suppression of inflammation and endoplasmic reticulum associated degradation. These observations suggest that these cysteines offer viable targets for therapies against COVID-19.
Wave-Mean-Flow Interactions

Many middle atmosphere phenomena, such as, for example, sudden stratospheric warmings, can be described in terms of the interaction between the zonal mean flow and eddy disturbances on the flow. In this section, wave-mean-flow interactions are discussed for extratropical phenomena, which are well described by quasi-geostrophic PV dynamics, and for the equatorial quasi-biennial oscillation (QBO).
Modelling and measuring the effects of public subsidies on business R&D: theoretical and econometric issues

It is the aim of this paper to review the principal econometric models used so far to measure the effect of government’s support to private RD in order to reach this task, we first present a basic theoretical framework to identify the effects of public subsidies on business RD 2. models using the subsidy variable in a continuous or in a binary form; and finally, 3. studies exploiting a cross-section versus a longitudinal (panel data) structure. The final part of the paper is an original contribution providing some guidelines to implement R&D policy evaluation in a dynamic subsidization setting.