cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of Salmonella enterica serovar typhimurium two-component system PreA/PreB in modulating PmrA-regulated gene transcription

The PmrA/PmrB two-component system encoded by the pmrCAB operon regulates the modification of Salmonella enterica serovar Typhimurium lipopolysaccharide leading to polymyxin B resistance. PmrA and PhoP are the only known activators of pmrCAB. A transposon mutagenesis screen for additional regulators of a pmrC::MudJ fusion led to the identification of a two-component system, termed PreA/PreB (pmrCAB regulators A and B), that controls the transcription of the pmrCAB operon in response to unknown signals. The initial observations indicated that insertions in, or a deletion of, the preB sensor, but not the preA response regulator, caused upregulation of pmrCAB. Interestingly, the expression of pmrCAB was not upregulated in a preAB mutant grown in LB broth, implicating PreA in the increased expression of pmrCAB in the preB strain. This was confirmed by overexpression of preA(+) in preAB or preB backgrounds, which resulted in significant upregulation or further upregulation of pmrCAB. No such effect was observed in any tested preB(+) backgrounds. Additionally, an ectopic construct expressing a preA[D51A] allele also failed to upregulate pmrC in any of the pre backgrounds tested, which implies that there is a need for phosphorylation in the activation of the target genes. The observed upregulation of pmrCAB occurred independently of the response regulators PmrA and PhoP. Although a preB mutation led to increased transcription of pmrCAB, this did not result in a measurable effect on polymyxin B resistance. Our genetic data support a model of regulation whereby, in response to unknown signals, the PreB sensor activates PreA, which in turn indirectly upregulates pmrCAB transcription.
Estimation With Response Error and Nonresponse

Error in survey data originates from failure to contact the sample and from false answers to verifiable questions. These errors may be systematic and associated with uncooperative or unreliable respondents. Zabel modeled attrition in the Survey of Income and Program Participation and found systematic demographic and design effects. Bollinger and David modeled response error and identified correlations to income per capita. In this analysis, we link missing interviews in a panel and response error through a trivariate probit analysis. Robustness of the correlation between attrition and response error is examined by comparing variants of the model. The joint model of response error and attrition becomes the first stage of a pseudolikelihood estimate of a model of food-stamp participation. The model is significantly different from naive probit on the survey data.
The Unstable Repeats - Three Evolving Faces of Neurological Disease

Disorders characterized by expansion of an unstable nucleotide repeat account for a number of inherited neurological diseases. Here, we review examples of unstable repeat disorders that nicely illustrate three of the major pathogenic mechanisms associated with these diseases: loss of function typically by disrupting transcription of the mutated gene, RNA toxic gain of function, and protein toxic gain of function. In addition to providing insight into the mechanisms underlying these devastating neurological disorders, the study of these unstable microsatellite repeat disorders has provided insight into very basic aspects of neuroscience.
Content and Language Integrated Learning: Evidence from Research in Europe edited by DE ZAROBE, YOLANDA RUIZ, & ROSA MARÍA JIMÉNEZ CATALÁN

The article reviews the book "Content and Language Integrated Learning: Evidence from Research in Europe," edited by Yolanda Ruiz De Zarobe and Rosa Maria Jimenez Catalan, part of the Second Language Acquisition series.
High Resolution Particle Image Velocimetry and CH-PLIF Measurements and Analysis of a Shear Layer Stabilized Flame

Understanding the mechanisms and physics of flame stabilization and blowoff of premixed flames is critical toward the design of high velocity combustion devices. In the high bulk flow velocity situation typical of practical combustors, the flame anchors in shear layers where the local flow velocities are much lower. Within the shear layer, fluid strain deformation rates are very high and the flame can be subjected to significant stretch levels. The main goal of this work was to characterize the flow and stretch conditions that a premixed flame experiences in a practical combustor geometry and to compare these values to calculated extinction values. High resolution, simultaneous particle image velocimetry (PIV) and planar laser induced fluorescence of CH radicals (CH-PLIF) measurements are used to capture the flame edge and near-field stabilization region. When approaching lean limit extinction conditions, we note characteristic changes in the stretch and flow conditions experienced by the flame. Most notably, the flame becomes less critically stretched when fuel/air ratio is decreased. However, at these lean conditions, the flame is subject to higher mean flow velocities at the edge, suggesting less favorable flow conditions are present at the attachment point of the flame as blowoff is approached. These measurements suggest that blowoff of the flame from the shear layer is not directly stretch extinction induced, but rather the result of an imbalance between the speed of the flame edge and local tangential flow velocity.
REIDEMEISTER MOVES ON 1-MANIFOLDS IN R×D2

In this paper we aim to set forth a notion of equivalence for 1-manifolds that are properly embedded in the space R×D2 and prove that this is the same as ambient isotopy.
Comparison of Methods for Estimating Ground-Water Pumpage for Irrigation

Ground-water pumpage for irrigation was measured at 32 sites on the eastern Snake River Plain in southern Idaho during 1983. Pumpage at these sites also was estimated by three commonly used methods, and pumpage estimates were compared to measured values to determine the accuracy of each estimate. Statistical comparisons of estimated and metered pumpage using an F-test showed that only estimates made using the instantaneous discharge method were not significantly different (α. = 0.01) from metered values. Pumpage estimates made using the power consumption method reflect variability in pumping efficiency among sites. Pumpage estimates made using the crop-consumptive use method reflect variability in water-management practices. Pumpage estimates made using the instantaneous discharge method reflect variability in discharges at each site during the irrigation season.
Perceptions of professionalism vary most with educational rank and age.

The purpose of this study was to assess whether the perception of what constitutes professionalism varies with age, discipline, gender, or educational level among students and faculty at the major academic health sciences center in West Virginia. This exploratory descriptive survey study asked participants to classify behaviors described in a survey as professional, unprofessional, or unrelated to professionalism. Results were analyzed using contingency tables. For 2 x 2 contingency tables, test of independence of homogeneity was carried out by using Fisher’s exact test. For tables of higher dimensions, chi square test was used. The survey yielded a 45 percent return rate and demonstrated that the perception of professionalism varied most with the level of education and age and, to a lesser extent, with gender and health care discipline. Undergraduates, females, the youngest age group (≤ 26), nursing students, and faculty other than dental or medical were more likely to label behavior depicted in the survey statements as unprofessional. The findings of this study underscore the complexities of the genesis of professionalism. Further study in regard to the teaching of professionalism is warranted.
Biological effects of Pseudomonas aeruginosa exotoxin A: Lymphoproliferation of T lymphocytes in athymic mice

Pseudomonas aeruginosa exotoxin A has been observed to exert modulatory effects on the immune response. The present study examines the ability of exotoxin A to induce proliferation of splenocytes from athymic nu/nu mice. We observed that exotoxin A induced the proliferation of athymic nude splenocytes which could be abrogated by heating the toxin at 70°C or by preincubation of the toxin with rabbit anti-exotoxin A antiserum. Photoaffinity-labelled toxin sigificantly induced splenocyte proliferation although the relative activity was reduced. Maximum nude splenocyte proliferation was observed at a toxin dose of 100 ng. This same dose was shown previously for athymic splenocytes to induce an enhanced response to the thymus-dependent (TD) antigen, sheep red blood cells (SRBC). The increased [3H]-TdR uptake in athymic splenocytes stimulated by exotoxin A was initiated by 24 hours and continued to day 10, Nude splenocytes depleted of Ig+ and Ia+ cells were induced to proliferate by exotoxin A. Cyclosporin A addition abrogated the ability of exotoxin A to induce proliferation. These results suggest that Pseudomonas aeruginosa exotoxin A can stimulate the proliferation of splenic T lymphocytes in athymic nu/nu mice.
Cylinder Orientation and Shear Alignment in Thin Films of Polystyrene–Poly(n-hexyl methacrylate) Diblock Copolymers

Thin films of cylinder-forming polystyrene–poly(n-hexyl methacrylate) diblock copolymers, PS–PHMA, are attractive as nanolithographic templates, an application which demands good control over the thin-film structure—yet the quality of order achieved to date in PS–PHMA films has fallen short of this ideal. In the present work, a series of PS–PHMA diblocks of varying composition, all forming PS cylinders, are synthesized and their morphology studied as a function of film thickness in both nonsheared and shear-aligned films. In nonsheared films, the cylinder axis orientation relative to the surface switches from parallel to perpendicular as a function of film thickness; this oscillation is damped out as the fraction of the cylinder-forming block (PS) increases, away from the sphere–cylinder phase boundary. In aligned films, thicknesses which possess the highest coverage of parallel cylinders prior to shear show the highest quality of alignment postshear, as measured by the in-plane orientational order parame...
Tertiary-amine-containing thermo- and pH-sensitive hydrophilic ABA triblock copolymers: effect of different tertiary amines on thermally induced sol-gel transitions.

This Article reports on the synthesis of a series of well-defined, tertiary-amine-containing ABA triblock copolymers, composed of a poly(ethylene oxide) (PEO) central block and thermo- and pH-sensitive outer blocks, and the study of the effect of different tertiary amines on thermally induced sol–gel transition temperatures (Tsol–gel) of their 10 wt % aqueous solutions. The doubly responsive ABA triblock copolymers were prepared from a difunctional PEO macroinitiator by atom transfer radical polymerization of methoxydi(ethylene glycol) methacrylate and ethoxydi(ethylene glycol) methacrylate at a feed molar ratio of 30:70 with ∼5 mol % of either N,N-diethylaminoethyl methacrylate (DEAEMA), N,N-diisopropylaminoethyl methacrylate, or N,N-di(n-butyl)aminoethyl methacrylate. The chain lengths of thermosensitive outer blocks and the molar contents of tertiary amines were very similar for all copolymers. Using rheological measurements, we determined the pH dependences of Tsol–gel of 10 wt % aqueous solutions of ...
Legal Protection for the Important Rights of the Mentally Incapacitated in the Process of Medical Assistance

There has been wide concern over the mental health issues in the international community.Many countries protect the important rights of the mentally incapacitated through legislation.Because there is no special laws and regulations for protecting the rights of the mentally incapacitated in China,this paper makes a comparative analysis of the advanced legislation and experience in practice for protecting the rights of the mentally incapacitated in the process of medical assistance,fully demonstrates the deficiency of the draft of Mental Health Act and the advantages and disadvantages of the two drafts of Mental Health Act with reference to legislation in many foreign countries and explores the omission in the draft of Mental Health Act.It is suggested that our Mental Health Act should conform to the international development,speed up the perfection of the legislation for protecting the important rights of the mentally incapacitated and maintain the integrity of private right system.
The Use of the Red Cell Surface Antigen to Predict the Malignant Potential of Transitional Cell Carcinoma of the Ureter and Renal Pelvis

AbstractThis is the first report on the use of the red cell surface antigen test in predicting the malignant potential of transitional cell carcinoma of the ureter and renal pelvis. In 29 cases evaluated there was an 80 per cent correlation. The red cell surface antigen determination was shown to have practical value in the management of these tumors.
The design, pedagogy and practice of an integrated public affairs leadership course

Current world events demand public affairs leadership training that generates among professionals a sense of capability, agency, and responsibility to engage in complex public problems. In this paper, we describe a unique course operated in the US focused on achieving these learning outcomes. It uses an unconventional schedule and course design that leverages information communication technologies to support learning. Its integrated model combines conventionally distinct courses with a pedagogical approach stressing experiential learning, personal reflection, and critical thinking. The paper describes the teaching practices used in the course, as well as offers three sources of evidence about what results from its implementation.
WAVE SCATTERING AND IMAGING

Acoustic scattering can be sorted into categories according to the size and shape of an object relative to the insonifying wavelength. Specular scatterers, those much larger than a wavelength, obey geometric laws. Unresolved scatterers well below a wavelength in size are diffusive and still exert a major influence on images by causing speckle, a fine-grained background texture in images. Scatterers lying in size and shape between these two extremes fall into the diffractive range. These scatterers change their acoustic scattering appearance dependent on their shape, size, material properties, and orientation relative to and characteristics and frequency content of an incident acoustic beam. The role of scattering is explained in the overall imaging process. Scattering from simply shaped objects is examined analytically and by the Born approximation. The effects of speckle on imaging are quantified by contrast ratio and statistical distributions. The back-scattered field from random media is described by an acoustic version of the van Cittert–Zernike theorem. Methods for speckle reduction in imaging are discussed. Speckle tracking is an important method of measuring tissue displacements and movement.
REGENERATIVE SPROUTING OF NORADRENERGIC TERMINALS IN THE CEREBELLUM

Neonatal treatment of rats with the neurotoxin 6-hydroxydopa (6-OHDOPA) (60μg/g i.p.) results in destruction of approximately 50% of the perikarya in the caudal locus coeruleus. When given to rats 3 days after birth 6-OHDOPA also causes a reduction in cerebellar norepinephrine (NE) content at 8 weeks-an effect completely reversed by nerve growth factor (NGF). These findings suggest that NGF will stimulate regeneration of developing noradrenergic nerves in the brain, or will protect the neurons from the destructive action of a neurotoxic substance.
“Abusive Furniture”: Visual Metonymy and the Hungarian Stop Violence Against Women Campaign

ABSTRACTIn this essay, we argue that Amnesty international’s media campaign against domestic violence unwittingly directs attention away from perpetrators of abuse to their victims. This reinforcement happens through the visual features of the campaign and, more specifically, through metonymic substitution. We examine three imagetexts from an Amnesty International media campaign in Hungary targeting domestic violence to better understand the function and implication of visual metonymy. Each imagetext features a woman next to a household object that metonymically replaces a perpetrator of domestic abuse. Using vector analysis, we suggest that compositional factors and text in each imagetext work together to focus attention on specific aspects of the image. In these imagetexts, metonymic substitution functions to hide the perpetrators of violence and instead focus attention on the victims for making excuses about their own victimization.
Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Posttreatment in Rhesus Macaques

Nonhuman primates currently serve as the best experimental model for Lyme disease because of their close genetic homology with humans and demonstration of all three phases of disease after infection with Borrelia burgdorferi. We investigated the pathology associated with late disseminated Lyme disease (12 to 13 months after tick inoculation) in doxycycline-treated (28 days; 5 mg/kg, oral, twice daily) and untreated rhesus macaques. Minimal to moderate lymphoplasmacytic inflammation, with a predilection for perivascular spaces and collagenous tissues, was observed in multiple tissues, including the cerebral leptomeninges, brainstem, peripheral nerves from both fore and hind limbs, stifle synovium and perisynovial adipose tissue, urinary bladder, skeletal muscle, myocardium, and visceral pericardium. Indirect immunofluorescence assays that combined monoclonal (outer surface protein A) and polyclonal antibodies were performed on all tissue sections that contained inflammation. Rare morphologically intact spirochetes were observed in the brains of two treated rhesus macaques, the heart of one treated rhesus macaque, and adjacent to a peripheral nerve of an untreated animal. Borrelia antigen staining of probable spirochete cross sections was also observed in heart, skeletal muscle, and near peripheral nerves of treated and untreated animals. These findings support the notion that chronic Lyme disease symptoms can be attributable to residual inflammation in and around tissues that harbor a low burden of persistent host-adapted spirochetes and/or residual antigen.
N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish

N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos. The effects of ketamine and N-acetylcysteine alone or in combination were measured on the heart rate, body length, brain serotonergic neurons and tyrosine hydroxylase-immunoreactive (TH-IR) neurons. In the absence of N-acetylcysteine, a concentration of ketamine that produces an internal embryo exposure level comparable to human anesthetic plasma concentrations significantly reduced heart rate and body length and those effects were prevented by N-acetylcysteine co-treatment. Ketamine also reduced the areas occupied by serotonergic neurons in the brain, whereas N-acetylcysteine co-exposure counteracted this effect. TH-IR neurons in the embryo brain and TH-IR cells in the trunk were significantly reduced with ketamine treatment, but not in the presence of N-acetylcysteine. In our continued search for compounds that can prevent ketamine toxicity, this study using specific endpoints of developmental toxicity, cardiotoxicity and neurotoxicity, demonstrates protective effects of N-acetylcysteine against ketamine's adverse effects. This is the first study that shows the protective effects of N-acetylcysteine on ketamine-induced developmental defects of monoaminergic neurons as observed in a whole organism.
Wer ist Serge Lang

Serge Lang wurde 1927 in Paris geboren. Bis zur neunten Klasse ging er in einem Pariser Vorort, wo er auch wohnte, zur Schule. Danach siedelte er in die USA uber. In Kalifornien besuchte er noch zwei Jahre die hohere Schule und begann dann sein Studium am California Institut of Technology (Caltech), das er 1946 abschlos. Nach anderthalb Jahren im amerikanischen Militardienst ging er an die Universitat Princeton. Zuerst verbrachte er ein Jahr am Philosophischen Institut. Dann wechselte er zur Mathematik uber und promovierte im Jahre 1951. Er lehrte an der Universitat Princeton und arbeitete ein Jahr am Institute for Advanced Study, ebenfalls in Princeton.
Terms, Models, and Resources

The goal of this book is to introduce the field of information retrieval (IR), with emphasis on the health care domain. To many, the term IR implies retrieving information of any type from a computer. However, to those working in the field, it has a different and more specific meaning: the retrieval of information from textual databases. It is a field at the intersection of information science and computer science, which concerns itself with the indexing and retrieval of information from heterogeneous textual databases.
Supporting All Students: Creating a Tiered Continuum of Behavior Support at the Classroom Level to Enhance Schoolwide Multi-Tiered Systems of Support.

The use of a tiered approach provides a structured format for increasing consistency across educators to address the diversity of student needs within a school. The same logic of providing a tiered...
Preservation of spinach by isochoric (constant volume) freezing

Efforts are currently directed towards improving the quality of vegetables after freezing and thawing. One of the methods under investigation is isochoric freezing. In this study, we evaluated isochoric freezing for preserving the quality of baby‐leaf spinach. We compared the properties of thawed spinach frozen to −4°C in an isochoric system with those of fresh spinach, thawed spinach frozen to −4°C in an isobaric system and thawed spinach that were commercially frozen. Spinach leaves frozen under isobaric conditions lost mass and thickness, making them softer and translucent. They also lost much of their nutrient content. In comparison, isochoric freezing maintained cell integrity and turgidity. Thawed leaves remained crunchy with characteristics similar to fresh leaves. Isochoric freezing also preserved nutritional content better than isobaric freezing, although significant nutrient losses still occurred.
Preparing High School Students With Chronic Illnesses for College Transition: Lessons Learned From College Counselors:

Interest is growing regarding high school preparation for students transitioning to college with chronic illnesses such as asthma, cancer, and diabetes. This qualitative study examined 15 college c...
Integrating Music into Couple Therapy Theory and Practice

Over the past three decades, the theory and practice of couple therapy has moved towards integrative approaches. Typically, two or more couple therapy theories and their associated practices are blended into a more comprehensive, flexible approach to conceptualizing and intervening with couples’ problems. Emerging findings from social and affective neuroscience are also increasingly incorporated. This article argues for broadening integrative efforts to include the perspectives and products of the arts and humanities into couple therapy, with a focus on music. The article presents the rationale for this broadened scope of integration by discussing E. O. Wilson’s consilience theory and its bearing on the distinctions and convergence among the science, craft, and art of therapy. The research on the neuroscience of music and the role of music in affective experience, expression, and intimate relationships strongly supports use of music in transformative work with couples. Music theory and arts provide a useful framework for creating novel theories about couple relationships, for observing and understanding distressed couples’ problematic patterns, and for formulating interventions. Sensitivity to the musical aspects of therapists’ communicative behavior can increase the impact of interventions. The article provides a practical framework for utilizing music in couple therapy, and includes several illustrative case examples.
Thermal and radiation response of 4H–SiC Schottky diodes with direct-write electrical contacts

A high-sensitivity 4H–SiC temperature sensor and an alpha detector have been fabricated using additively printed metal contacts. The surface morphology and electrical conductivity of the printed electrodes were established prior to Schottky diode development. 4H–SiC Schottky diodes with direct-write printed silver contacts on the 5 μm-thick epilayer on 4H–SiC were characterized electrically in terms of the forward and reverse current–voltage and high-frequency capacitance–voltage characteristics. The turn-on voltage of the Schottky diodes, as established from the forward current–voltage characteristics measured up to a temperature of 400 °C, showed a linear temperature dependence. Schottky diodes with direct-write printed Ag electrodes were able to measure alpha particles emitted from Americium-241. The high temperature and radiation response of the Schottky diodes show their suitability for multi-modal sensor fusion on the 4H–SiC platform for harsh environment applications.
Racial and ethnic differences in medication use among beneficiaries of social security disability insurance with rheumatoid arthritis.

Abstract Objective To determine racial/ethnic differences in the use of conventional synthetic or biologic disease-modifying anti-rheumatic drugs (csDMARDs or bDMARDs, respectively) and long-term glucocorticoids (GC) or opioids among beneficiaries of the Social Security Disability Insurance (SSDI) with rheumatoid arthritis (RA) and Methods Serial cross-sectional analyses of Centers for Medicare and Medicaid Services claims data (2007, 2011, and 2014) for individuals Results There were 12,931; 15,033; and 15,599 participants in 2007, 2011, and 2014, respectively. The overall use of csDMARD without bDMARD among beneficiaries of the SSDI were 31.1%, 30.3%, and 29.2%; 50.2%, 51.7%, and 53.8% used bDMARDs; 37.6%, 36.1%, and 34.4% used long-term GC; and 61.1%, 63.8%, and 63.7% used long-term opioids in years 2007, 2011, and 2014 respectively. The use of csDMARDs without bDMARDs was higher and the use of bDMARDs was lower among Blacks compared to Whites (adjusted absolute difference: +3.0%, +5.0%, and +3.3% for csDMARDs without bDMARDs and –4.6%, –5.7%, and –4.0% for bDMARDs in 2007, 2011, and 2014, respectively; all p Conclusion Racial and ethnic differences exists in regards to the treatment of RA among beneficiaries of the SSDI. These findings suggest that this already vulnerable population of patients with RA can also have a racial and ethnic disparity that can contribute to additional disease burden and that should be examined in order to inform future interventions or even inform future policy changes to the SSDI.
Does democratic progress deter terrorist incidents

Abstract This paper examines the democracy-terrorism linkage that can be distinguished at different stages of democracy. We first attempt to identify the level of democracy where terrorism is peaked, and then investigate if there is a significant reduction of terror incidents as a country advances to higher levels of democracy from the peaked level of terrorism. Using data from 124 countries covering the period 1984–2017, the study finds that the terrorism-increasing effect of democratization is peaked when a country is at the very middle level of democracy. Furthermore, there is evidence that terrorism may not be deterred as a country incrementally progresses to higher levels of democracy from the peak unless the country reaches the very highest level of democracy. The study also presents evidence that terror attacks become more prevalent with a lower level of economic development, a larger population, or an increase in instability of governance. However, economic growth, urbanization, and globalization are not significantly related to terrorism.
Identifying Errors in Service Transformer Connections

Distribution system models play a critical role in the modern grid, driving distributed energy resource integration through hosting capacity analysis and providing insight into critical areas of interest such as grid resilience and stability. Thus, the ability to validate and improve existing distribution system models is also critical. This work presents a method for identifying service transformers which contain errors in specifying the customers connected to the low-voltage side of that transformer. Pairwise correlation coefficients of the smart meter voltage time series are used to detect when a customer is not in the transformer grouping that is specified in the model. The proposed method is demonstrated both on synthetic data as well as a real utility feeder, and it successfully identifies errors in the transformer labeling in both datasets.
Evaluating the incidence of chemotherapy-induced nausea and vomiting in patients with B-cell lymphoma receiving dose-adjusted EPOCH and rituximab:

BackgroundStudies evaluating antiemetic prophylaxis have primarily focused on the solid tumor setting and single-day regimens. This study evaluates antiemetic prophylaxis and chemotherapy induced n...
Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry.

The state of Kentucky has the highest cancer incidence and mortality in the United States. High-risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution. Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate-high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts. PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high-TMB cohort compared to low-intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real-world data publications which might help determine biomarkers that could benefit specific populations.
Neuroendocrine Tumors of the Thyroid and Their Mimics

This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical "tips" for the practicing pathologist.
Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells

Clofarabine, an FDA approved purine analog, is used in the treatment of relapsed or refractory acute lymphoblastic leukemia. Clofarabine acts by inhibiting DNA synthesis. We demonstrated that clofarabine may have a novel function though inhibiting CD99, a transmembrane protein highly expressed on Ewing Sarcoma (ES) cells. CD99 is a validated target in ES whose inhibition may lead to a high therapeutic index for patients. Here we present additional data to support the hypothesis that clofarabine acts on CD99 and regulates key signaling pathways in ES. Cellular thermal shift assay indicated a direct interaction between clofarabine and CD99 in ES cell lysates. Clofarabine induced ES cell death does not require clofarabine's conversion to its active form by deoxycytidine kinase. A phosphokinase array screen with clofarabine and a CD99 blocking antibody identified alterations in signaling pathways. CD99 inhibition with clofarabine in ES cells caused rapid and sustained phosphorylation of ERK, MSK, and CREB. However, activation of this pathway did not correlate with clofarabine induced ES cell death. In summary, we demonstrated that clofarabine may activate ERK, MSK, and CREB phosphorylation through CD99 within minutes, however this paradoxical activation and subsequent ES cell death requires additional investigation.
Racial and Ethnic Residential Segregation by Family Structure and the Presence of Children in Metropolitan America

Little research has examined the residential segregation of blacks, Hispanics, and Asians from whites disaggregated by family structure and the presence of children in metropolitan America. Using data from the 2010 Census and the 2006–2010 American Community Survey, we find that, net of controls, among blacks, single-mother families are significantly more segregated from whites than married couples, regardless of the presence of children. However, these same differences in segregation are not found among Hispanics and Asians. Among those groups, married families with children under 18 are more segregated from whites than married families without children under 18, suggesting that married Hispanics and Asians with children desire closer proximity to their co-ethnics. The results suggest that racial and ethnic segregation by family structure and the presence of children varies by the racial and ethnic group considered and is, therefore, important to understanding overall racial and ethnic segregation in metropolitan America.
Association of Increased Serum Lipopolysaccharide but not Microbial Dysbiosis with Obesity-related Osteoarthritis.

OBJECTIVE To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). METHODS Stool and blood samples were collected from 92 participants with BMI ≥ 30 kg/m2 recruited from the Johnston County Osteoarthritis Project. OA cases (n=50) had hand plus knee OA (Kellgren-Lawrence [KL] grade ≥2 or arthroplasty). Controls (N=42) had no hand OA and KL grade 0-1 knees. Compositional analysis of stool samples was carried out by 16S rRNA amplicon sequencing. Alpha and beta diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with case or control pooled fecal samples and placed on a 40% fat, high sucrose diet for 40 weeks. Knee OA was evaluated histologically. RESULTS OA cases were slightly older with more females and higher BMI, WOMAC pain and KL grades than controls. There were no significant differences in alpha or beta diversity or genus level composition between cases and controls. Cases had higher plasma levels of osteopontin (p=0.01) and serum LPS (p<0.0001). Mice transplanted with case or control microbiota exhibited a significant difference in alpha diversity (p=0.02) and beta diversity but no differences in OA severity. CONCLUSION The lack of differences in the gut microbiota yet increased serum LPS levels suggest the possibility that increased intestinal permeability allowing for greater absorption of LPS, rather than a dysbiotic microbiota, may contribute to development of OA associated with obesity.
A Study Abroad Experience in Ireland: The Celtic Tiger Before and After the Global Financial Crisis

This chapter describes a study abroad program to Ireland, a faculty-led 5-week program that was taught on the University College Dublin campus. This program included instruction in two courses, one on Financial Economics and one on the Economic Development of Ireland. It included weekly travel to locations throughout Ireland, from an excursion to Galway that included visits to the Connemara region and the Cliffs of Moher in the Burren, to an excursion to Belfast that included visits to the Peace Walls, the various shrines in Belfast, and including travel to the north coast to see the Giant’s Causeway. The program consisted of 15–20 students and one faculty instructor, and proved quite popular.
Development and Impact of a Novel Academic Primary Care Compensation Model

Background Traditional productivity-based compensation models do not align well with newer population-based approaches to primary care. There are few published examples of academic general internal medicine compensation models that explicitly reward population health management, including care for patients between visits.
The relevance of tomatinase activity in pathogens of tomato: disruption of the β2-tomatinase gene inColletotrichum coccodes and Septoria lycopersici and heterologous expression of the Septoria lycopersiciβ2-tomatinase in Nectria haematococca, a pathogen of tomato fruit

Abstract Many fungal pathogens of tomato have the ability to enzymatically detoxify the toxic steroidal glycoalkaloid α-tomatine, synthesized by Lycopersicon and some Solanum species. However, it is unclear whether detoxification of this phytoanticipin is involved in the ability of these fungi to parasitize tomato. We have taken two approaches to address this question. For one approach, we have reduced or eliminated this enzymatic function by transformation-mediated disruption of the gene encoding β2-tomatinase in Colletotrichum coccodes andSeptoria lycopersici . Gene disruption of the S. lycopersiciβ2-tomatinase gene in an albino strain resulted in both a loss of β2-tomatinase activity and a loss of tolerance to α-tomatine. The results of pathogenicity tests with this mutant were inconclusive due to the lack of pathogenicity of the albino mutant. Disruption of the β2-tomatinase gene in C. coccodes resulted in a loss of β2-tomatinase activity but these mutants retained their tolerance to α-tomatine and their abilities to degrade α-tomatine via other enzyme(s). The gene-disrupted mutants were as pathogenic as wild type isolates on green tomato fruit, an organ containing high levels of α-tomatine. For our other approach, we have expressed the S. lycopersiciβ2-tomatinase gene in a tomatine tolerant mutant of Nectria haematococca MPVI, a fungus that normally can infect ripe but not green tomato fruit. Expression of β2-tomatinase in this N. haematococca mutant enabled it to detoxify α-tomatine and resulted in its ability to parasitize green tomato fruit.
High-intensity focused ultrasound ablation enhancement in vivo via phase-shift nanodroplets compared to microbubbles

During high-intensity focused ultrasound (HIFU) surgical procedures, there is a need to rapidly ablate pathological tissue while minimizing damage to healthy tissue. Current techniques are limited by relatively long procedure times and risks of off-target heating of healthy tissue. One possible solution is the use of microbubbles, which can improve the efficiency of thermal energy delivery during HIFU procedures. However, microbubbles also suffer from limitations such as low spatial selectivity and short circulation time in vivo. In this study, the use of a dual-perfluorocarbon nanodroplet that can enhance thermal ablation, yet retains high spatial selectivity and circulation half-life, was evaluated in vivo and compared to traditional microbubble agents during HIFU ablations of rat liver. High-intensity focused ultrasound (1.1 MHz, 4.1 MPa, 15-s continuous wave) was applied to rat liver in vivo, and heating was monitored during sonication by magnetic resonance thermometry. Thermometry data were analyzed to quantify temperature rise and ablated area, both at the target and prefocally, for HIFU applied 5, 15, or 95 min after intravenous injection of either nanodroplet or microbubble agents. Sham control experiments (no injected agents) were also performed. At all three time points, nanodroplets significantly enhanced thermal delivery to the target, achieving temperatures 130 % higher and ablated areas 30 times larger than no-agent control sonications. Nanodroplets did not significantly enhance off-target surface heating. Microbubbles also resulted in significantly greater thermal delivery, but heating was concentrated at the proximal surface of the animal, causing skin burns. Furthermore, microbubbles resulted in lower thermal delivery to the desired target than even the control case, with the notable exception of the 95-min time point. Results indicate that the nanodroplet formulation studied here can substantially increase thermal delivery at the acoustic focus while avoiding prefocal heating. In contrast, microbubbles resulted in greater prefocal heating and less heating at the target. Furthermore, nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 h after injection. The use of a dual-perfluorocarbon nanodroplet formulation as described herein could substantially reduce HIFU procedure times without increasing the risk of skin burns.
On Large Deviation Convergence of Invariant Measures

We present new results on the connection between large deviation principles for trajectories of stochastic processes and the associated invariant measures. Applications to diffusion and queuing processes are provided.
Using Classroom Demonstrations in Familiar Nonlegal Contexts to Teach Unfamiliar Concepts of Legal Method to New Students

In their first semester of law school, students are quickly immersed in a sea of appellate opinions, punctuated with scattered islands of statutory text. With guidance from their classroom instructors, and especially from their instructor in legal method and writing, they begin to see patterns emerging from the judicial opinions, and they eventually begin constructing a working knowledge of the elements of legal method and analysis. Students eventually come to realize that their assimilation of the current landscape of settled legal rules is secondary to their mastery of legal method. To help students understand their academic task, we can try to build on their schemata, their existing foundations of knowledge. By relating a new concept to a student's existing intellectual foundation, we can help the student to assimilate the new concept more quickly. This essay gives two examples of classroom demonstrations designed to introduce first-semester law students to concepts of legal method that tend to cause difficulty for some of them if expressed only in abstract terms. These demonstrations illustrate: (1) the inherent uncertainty or indeterminacy in most legal questions, particularly in the problems that we are likely to assign as vehicles for developing skills of analysis and advocacy; and (2) the process of deriving a larger legal picture from a series of cases by synthesizing the cases, each of which may build on previous ones in the process of incremental judicial decision-making.
Relative K-Theory

We define a collapsing or trivialization procedure for bundles over X which yields a bundle over X / A for a closed subset A of X. With this construction we are able to give alternative descriptions of \(K(X,A) = \tilde K(X/A).\). For a finite CW-pair (X, A) we can define an exact sequence K(A) ← K(X) ← K(X, A) ← K(S(A)) ← K(S(X)), using an appropriate “coboundary operator.” With this sequence we see that in some sense the K-cofunctor can be used to define a cohomology theory.
Bound by Laws, or by Values? A Multi‐Level and Cross‐National Approach to Understanding the Protection of Minority Owners in Family Firms

Manuscript Type Conceptual Research Question/Issue How do firm-level attributes and country-level institutions affect cross-national and firm-level differences in how minority owner rights in family firms are protected? Research Insights We consider differences in family dynamics, stewardship-oriented organizational culture, and countries' legal and cultural dimensions to develop theory predicting differences in minority owner protection in family firms. We advance propositions and a model delineating the role of these key firm-level and country-level constructs. Theoretical/Academic Implications We contribute to the literature in three ways: (1) We illustrate the importance of family dynamics for predicting the likelihood of a stewardship-oriented culture to emerge in a family firm; (2) our multi-level and cross-national approach extends earlier explanations of agency and stewardship that are centered at the firm, family, and individual levels of analysis; and (3) we consider the impact of cross-cultural dimensions on family firms, an area that has received limited attention in the literature. Practitioner/Policy Implications Our research implies that individuals considering becoming a minority owner in a family firm should take into account not only the legal institutions of that country (which might not be as strong as they first seem) but also intra-firm family dynamics and the prevalent norms and values of the firm's national culture to get a more complete picture of the protections available to them.
Cyclical Changes in Susceptibility of a Myeloma Tumor (LPC-1) to Immune Destruction III. Periodic Production of a Cell Surface Glycoprotein and Changes in Reactivity with Cytotoxic T Cells and anti-H-2D Sera

Previous studies showed that when LPC-1 myeloma cells were grown as ascites tumor cells in syngeneic (BALB/c) mice, the cells harvested after 2 to 4 days of growth (“early” cells) were susceptible to lysis by cytotoxic T lymphocytes (CTL) and highly reactive with anti-H-2 d antisera. Cells harvested after 12 to 14 days of growth (“late” cells) were resistant to lysis by CTL and poorly reactive with anti-H-2 d antisera. The present study shows that exposure to trypsin or chymotrypsin or subtilisin (but not to thrombin or Staphylococcus A protease) promptly converts LPC-1 cells with the late phenotype into cells with the early phenotype. Comparison of radiolabeled cell surface proteins by gel electrophoresis showed that the late cells possess a prominent trypsin-sensitive, high m.w. (160,000 daltons) surface glycoprotein that is present in smaller amounts on the early LPC-1 cells. This glycoprotein (gp160) was not detectable in four other BALB/c tumors that do not undergo the early-late transition of LPC-1. That gp160 was produced by LPC-1 cells, rather than adsorbed by these cells as they grow in vivo , was evident from the presence of an indistinguishable metabolically labeled glycoprotein on cultured LPC-1 cells.