cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3343: Targeting thyroid cancer stem cells with PPARγ agonists

Ligand activation of PPARγ is reported to inhibit proliferation and promote differentiation in many tissue types, including thyroid. Nonetheless, clinical trials treating thyroid cancer with the PPARγ agonist rosiglitazone yielded disappointing results when the measured outcomes were reacquisition of radioiodine uptake and overall survival. We report here evidence that PPARγ agonists preferentially target cancer stem cells and may still be useful for treatment of thyroid cancer in a different context, especially in combination with reagents that can target the remaining bulk of the tumor. We used for our studies FTC236 and FTC238, two related cell lines derived from follicular thyroid carcinoma metastases to lymph node and lungs. Both cell lines had robust PPARγ expression and harbored no known PPARγ fusion protein. Stem cell populations within the cell lines were measured using the Aldefluor (Aldf) assay for Aldehyde Dehydrogenase activity. Both cell lines have 5-10% Aldf+ cells. Populations which contained Aldf+ were the only ones capable of forming passageable sphere colonies in serum free suspension cultures and the only ones capable of forming tumors in NOD/SCID mice. Furthermore, FTC populations grown as spheres had six times more Aldf+ cells than those grown on plastic; therefore serum free suspension cultures was an effective way to enrich for FTC stem cells. FTC cells grown on plastic expressed PPARγ at five times the level seen in FTC spheres. We activated PPARγ signalling in FTC cells by addition of rosiglitazone or CAY10410, a chemical analogue of the natural PPARγ agonist 15-deoxy-Δ12,14-Prostaglandin-J2. At concentrations which exhibited less than 50% growth inhibitory effects, PPARγ agonists reduced the Aldf+ percentage of the treated population by 90%. Addition of PPARγ agonists into suspension cultures at the same concentrations reduced sphere formation by 80%. We identified the Aldefluor positive fraction as the tumorigenic and sphere-forming cancer stem cell population within our FTC cell lines. This population exhibited reduced PPARγ expression and was depleted upon treatment with PPARγ agonists. We hypothesize that downregulation of PPARγ signalling is required for maintenance of the stem cell phenotype and that induced activation of PPARγ is a possible strategy for targeting thyroid cancer stem cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3343.
Time/mortality relationships for Anastrepha suspensa (Diptera : Tephritidae) eggs and larvae submerged in hot water

Time/mortality ‘relationships were determined for eggs and 1- to 2-d-old and mature third-instar Caribbean fruit fly, Anastrepha suspensa (Loew), exposed to hot water. When eggs were submerged in water at 43.3, 46.1, 48.9, 51.7, or 54.4°C, estimated submersion times for 99% mortality were 24.8, 8.3, 2.0, 1.2, and 0.9 min, respectively; when larvae 1–2 d old were submerged in water at 43.3, 46.1, 48.9, 51.7, or 54.4°C, estimated submersion times for 99% mortality were 30.7, 6.6, 2.4, 1.5, and 0.7 min, respectively. When mature third instars were submerged in water at 40.56, 41.94, 43.3, 46.1, 48.9, 51.7, or 54.4°C, projected submersion times for 99% mortality were 77.8, 43.7, 13.5, 5.3, 2.0, 1.3, and 1.6 min, respectively. At 43.3 and 46.1°C, eggs were more resistant to heat than mature larvae and at 43.3°C, 1- to 2-d-old larvae were more resistant than mature larvae. The data may be useful in determining suitability of hot-water submersion treatments for disinfesting commodities attacked by A. suspensa and for comparing hot-water tolerance of A. suspensa with that of other tephritid species.
PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM

BACKGROUND: The PI3K pathway is activated in most GBMs and represents a potential therapeutic target. Buparlisib is an oral, pan-Class I PI3K inhibitor that enters the brain at therapeutic concentrations and inhibits the growth of U87 and human glioma tumor sphere models. METHODS: The Ivy Consortium conducted a phase II study of buparlisib in recurrent GBM patients with activation of the PI3K pathway (mutation, homozygous deletion or loss of IHC of PTEN, PIK3CA or PIK3RI mutations, or detectable pAKT). Additional eligibility criteria included radiologic progression, 1st or 2nd relapse, >18 yrs, KPS >60, adequate bone marrow and organ function, no prior bevacizumab or enzyme-inducing antiepileptic drugs. Patients received buparlisib 100mg daily. The study consisted of 2 concurrent cohorts. In Cohort 1 (up to 15 patients) buparlisib was given for 8-12 days prior to surgery for recurrent disease. Patients underwent FDG PET, pharmacokinetic studies, and tumor was obtained for drug concentrations and pharmacodynamic effects. In Cohort 2, 50 patients with unresectable GBM received buparlisib with a primary endpoint of PFS6. RESULTS: 13 patients were enrolled into cohort 1, 50 into cohort 2. Treatment was fairly well-tolerated with no grade 4 toxicities. Grade 3 toxicities were asymptomatic lipase elevation (6), rash (4), hyperglycemia (3), fatigue (4), elevated ALT/AST (2), and 1 each with depression, anxiety, hypophosphatemia, thrombocytopenia and lymphopenia. Analysis of tumor specimens from Cohort 1 showed reduction of pAKT by IHC in 4/6 (67%) of evaluable patients. The combined cohorts showed minimal efficacy with median PFS of 1.8 months and median OS of 10.9 months. Best response was stable disease. Only 1 patient in each cohort achieved PFS6. Of the first 40 patients who underwent exome sequencing, there were 4 PIK3CA (10%), 2 PIK3R1 (5%) and 13 PTEN (33%) mutations. Patients with PTEN loss and or PI3K mutations paradoxically had a worse outcome. CONCLUSIONS: Buparlisib is well-tolerated in patients with recurrent GBM and achieves adequate tumor concentration to inhibit pAKTS473. However, single agent efficacy was minimal. Final correlation of tumor genotype with outcome will be presented. SECONDARY CATEGORY: n/a.
Treatment of the shoulder-hand syndrome.

Prophylactic treatment of the shoulder-hand, syndrome following acute myocardial infarction or anginal attack should start while the patient is confined to bed.Active motion of the arm helps overcome splinting, atrophy and osteoporosis, and may overcome lymphatic and venous stasis. Concomitant use of cortisone lessens pain and spasm.
How to marry a disease: epidemics, contagion, and a magic ritual against the 'hand of the ghost'.

To test whether the Babylonians had a 'rational' explanation of contagion, some letters from Mari mentioning epidemics and contagious diseases are studied within the wider context of Babylonian medicine. Descriptions of similar cases are adduced from other cuneiform sources. In particular, one later magical text from Bogazkoy with instructions to marry a doll to an illness demon shows striking similarities with the terminology of the Mari letters. This points toward a magico-religious concept of contagiousness in which disease can be transmitted intentionally, or accidentally leap from one individual who has incurred the wrath of a god to an unwary other person.
Renal Transplantation into the Dysfunctional Bladder: The Role of Adjunctive Bladder Reconstruction

AbstractA retrospective review of pediatric renal transplantation at 3 centers identified 9 patients who had undergone major bladder reconstruction. Seven patients underwent bladder augmentation (5 gastric, 1 colonic, 1 ureteral) and 2 received gastric neobladders. Six patients required Mitrofanoff neourethras. Patient survival was 100% with initial graft survival of 56% during a mean followup of 29.4 months. Eight patients (89%) are presently dialysis-free with functioning allografts and all 9 (100%) are continent of urine. We conclude that renal transplantation and reconstruction to ensure continence are justifiable in even the most anatomically compromised children with end stage renal disease. It is essential that the pediatric urologist should have an integral role in the management of such cases.
UV-Photoinhibition : Studies in vitro and in Intact Plants

Plants exposed to intense illumination undergo an inhibition of photosynthesis in a process called photoinhibition. Early studies of photoinhibition, using chloroplasts and monochromatic light, identified two spectral ranges of photoinhibitory light, which gave rise to somewhat different effects (1–4). The action spectrum showed a UV light effect, mainly in the UV-B range, and a visible light effect. The quantum yield in the UV range was about a hundredfold greater than that in the visible range, which had the action spectrum of photosynthetic pigments. The UV-photoinhibition was specifically related to PS II. Some controversy exists as to whether the locus of UV-photoinhibition lies on the donor (1–9) or acceptor (10–12) side of PS II. It has also been suggested that in plants, the action spectrum of UV photoinhibition may reflect DNA damage (13). This work represents an attempt to further clarify the mechanism of UV-photoinhibiton of PS II in isolated PS II preparations, chloroplasts and intact plants.
Inhibition of granulocyte chemotaxis by hemoglobin in experimental peritonitis.

Viable bacteria injected intraperitoneally are not lethal to experimental animals unless hemoglobin (Hgb) or other adjuvant substances are simultaneously present (DAVIS, 1962), but Hgbs exact mechanism of action remains unclear. SIMMONS (1968) has shown that the adjuvant action of Hgb in experimental peritonitis is based on the ability of Hgb to delay the clearance of bacteria from the peritoneal cavity. Methods In vivo experiments. 312 female Sprague-Dawley rats weighing between 150 g and 200 g were used in these experiments. As ino­ culum a strain of E. coli isolated from a clinical human infection was used. Bacterial concentration was determined by measuring the light transmission in a Klett densitometer. The experimental animals were injected i.p. with the desired number of bacteria suspended in normal saline or in a solution of crystalized, lyo­ philized bovine Hgb in different concentrations. Serial bacterial colony counts, white blood cell (WBC) and differential counts from peritoneal irrigation fluid were obtained after inoculation. In vitro experiments. Polymorphonuclear granulocytes (PMN) were purified from heparinized human blood by the method of BOYUM (1968). Chemotaxis under agarose was then determined according to the method of NELSON (1975). Zymosan activated serum (ZAS) and E. coli culture filtrate (BFE) were used as chemotactic fac­ tor. In order to determine the influence of Hgb on the chemotactic response of PMNs lyophilized, crystalized human Hgb was added in different concentrations either to the chemotactic factor or the PMNs themselves.
Examining the Orthodoxy — Hobbes and Royalism

Hobbes was a royalist. He supported Charles I during the English Civil War and advocated absolutism of the most extreme variety. He argues that the subjects give up all their rights to the sovereign (except for the bare right to self-defence, which is rendered meaningless by the sovereign’s absolute power). He can be grouped together with other royalist thinkers and writers of his time, such as Sir Robert Filmer, Bishop Bramhall and Dudley Digges. His royalism is expressed and supported in his political writings.
Correspondence, MARGIE, Concept

Having discussed Winograd’s system in some detail, I would like to touch on some more general considerations and then turn to other research relevant to issues raised in that discussion.
Um cristão-novo nos trópicos: expansão imperial e identidade religiosa nos Diálogos das grandezas do Brasil de Ambrósio Fernandes Brandão

Os Dialogos das grandezas do Brasil (daqui em diante Dialogos), atribuidos ao cristao-novo1 portugues Ambrosio Fernandes Brandao (1555–1618?), foram redigidos em 1618 no nordeste do Brasil, provave...
Cognitive Framework of Set-Theoretic Methodology of Analysis and Synthesis: Categorization, Classification and Many Faces of Digital Geometry

Both approaches to so-called visual analysis have set-theoretic expression, based on the assumption that visual cognition takes place at the level of classes. The analytic approach has combined classical fuzziness with other generalizations of set theory such as rough and near sets. But a cursory examination of the terms of application of the set-theoretic formalism brings out problems and features that set the pictorial case apart from the linguistic alongside their similarities.
SPECIES OF MEAT ANIMALS | Poultry

Poultry meat has become a predominate source of protein in the US. This article reviews the historical production, present production, and nutritional value of the predominant poultry meat species (chicken and turkeys), and poultry species that have a much smaller presence in the marketplace.
The use of historical datasets to develop multi-trait selection models in processing tomato

Multi-trait indices (MTI) weigh traits based on their importance to facilitate selection in plant and animal improvement. In animal breeding, economic values are used to develop MTIs. For vegetables, economic data valuing traits are rarely available. We posit that varieties with traits valued by growers and processors achieve higher market share and longer life span. Our objective was to develop MTIs predicting success of tomato varieties. Historical data for the California processing tomato industry from 1992 to 2013 provided measurements for yield, soluble solids (Brix), color, pH, market share, and life span for 258 varieties. We used random models to estimate best linear unbiased predictors (BLUPs) for phenotypic traits of each variety, and evaluated trends over time. Yield has been increasing from 2006, while Brix stayed constant. Because yield and Brix are negatively correlated, this trend suggests that Brix influenced selection. The average number of resistances reported in varieties ranking in the top ten increased from 2 to 4.5 between 1992 and 2013. MTIs predicting success from phenotypic traits were developed with general linear models and tested using leave-one-out cross validation. MTIs weighing yield, Brix, pH and color were significantly correlated to success metrics and selected a significantly higher proportion of successful varieties relative to random sampling. The index multiplying yield and brix, suggested in the literature, was not significantly correlated with variety success. The MTIs suggested that fruit quality had less of an influence on variety success than yield. The MTIs developed could help improve gain under selection for quality traits in addition to yield.
Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and Intravenous Tissue Plasminogen Activator

Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. For patients who present with an acute stroke despite dabigatran therapy, clinical data on the use of intravenous tissue plasminogen activator (IV-tPA) is limited. There is an anticipated increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in patients on dabigatran therapy. In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran. Dabigatran reversal with idarucizumab before administration of IV-tPA might reduce the risk of sICH. We report a case of a 69-year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who presented with an initial National Institutes of Health Stroke Scale (NIHSS) of 12. There was no early evidence of ischemic stroke or hemorrhage on head computed tomography, and coagulation studies implied therapeutic dabigatran levels. After controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA was administrated beginning 197 minutes after he was last seen at his baseline. Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated that he was at his prestroke baseline, except for a complaint of worsened short-term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and should be considered for acute stroke patients arriving in the IV-tPA time window.
Unpacking Student Privacy

The learning analytics and education data mining discussed in this handbook hold great promise. At the same time, they raise important concerns about security, privacy, and the broader consequences of big data-driven education. This chapter describes the regulatory framework governing student data, its neglect of learning analytics and educational data mining, and proactive approaches to privacy. It is less about conveying specific rules and more about relevant concerns and solutions. Traditional student privacy law focuses on ensuring that parents or schools approve disclosure of student information. They are designed, however, to apply to paper “education records,” not “student data.” As a result, they no longer provide meaningful oversight. The primary federal student privacy statute does not even impose direct consequences for noncompliance or cover “learner” data collected directly from students. Newer privacy protections are uncoordinated, often prohibiting specific practices to disastrous effect or trying to limit “commercial” use. These also neglect the nuanced ethical issues that exist even when big data serves educational purposes. I propose a proactive approach that goes beyond mere compliance and includes explicitly considering broader consequences and ethics, putting explicit review protocols in place, providing meaningful transparency, and ensuring algorithmic accountability.
Infrared Laser Ablation with Vacuum Capture for Fingermark Sampling

Infrared laser ablation coupled to vacuum capture was employed to collect material from fingermarks deposited on surfaces of different porosity and roughness. Laser ablation at 3 μm was performed in reflection mode with subsequent capture of the ejecta with a filter connected to vacuum. Ablation and capture of standards from fingermarks was demonstrated on glass, plastic, aluminum, and cardboard surfaces. Using matrix assisted laser desorption ionization (MALDI), it was possible to detect caffeine after spiking with amounts as low as 1 ng. MALDI detection of condom lubricants and detection of antibacterial peptides from an antiseptic cream was demonstrated. Detection of explosives from fingermarks left on plastic surfaces as well as from direct deposition on the same surface using gas chromatography mass spectrometry (GC-MS) was shown.
Conducting Research on Adolescent Substance Abuse

Adolescents represent a challenging population for substance abuse research. Adolescence is a time of experimentation with many health risk behaviors including alcohol, tobacco, and other drug (ATOD) use with a potential for lifetime health consequences, including dependence. Despite recent decreases in adolescents’ use of certain illicit drugs such as cocaine, hallucinogens, and LSD, use of marijuana remains an area of significant concern. Another area of concern is the nonmedical use of prescription medications. Abuse of alcohol among adolescents and young adults also remains problematic. Some adolescent groups are more at risk than others, including runaway or “throwaway” youth, homeless youth and youth in juvenile detention or foster care. This chapter explores key issues in substance abuse in adolescent populations. Current research on the incidence and prevalence of substance use among youth is reviewed, with a focus on national surveys such as the Youth Risk Behavior Survey, the National Survey of Drug Use and Health, and the Monitoring the Future Study. Obstacles to conducting substance abuse research are also explored, including Institutional Review Board considerations and youth assent/consent issues. National Advisory Council on Drug Abuse Guidelines for Substance Abuse Research Involving Children and Adolescents are presented in their entirety to assist researchers seeking to conduct research on this population.
Herbicide injury induces DNA methylome alterations in Arabidopsis

The emergence of herbicide-resistant weeds is a major threat facing modern agriculture. Over 470 weedy-plant populations have developed resistance to herbicides. Traditional evolutionary mechanisms are not always sufficient to explain the rapidity with which certain weed populations adapt in response to herbicide exposure. Stress-induced epigenetic changes, such as alterations in DNA methylation, are potential additional adaptive mechanisms for herbicide resistance. We performed methylC sequencing of Arabidopsis thaliana leaves that developed after either mock treatment or two different sub-lethal doses of the herbicide glyphosate, the most-used herbicide in the history of agriculture. The herbicide injury resulted in 9,205 differentially methylated regions (DMRs) across the genome. In total, 5,914 of these DMRs were induced in a dose-dependent manner, wherein the methylation levels were positively correlated to the severity of the herbicide injury, suggesting that plants can modulate the magnitude of methylation changes based on the severity of the stress. Of the 3,680 genes associated with glyphosate-induced DMRs, only 7% were also implicated in methylation changes following biotic or salinity stress. These results demonstrate that plants respond to herbicide stress through changes in methylation patterns that are, in general, dose-sensitive and, at least partially, stress-specific.
From SNPs to Functional Studies in Cardiovascular Pharmacogenomics

Functional studies can be utilized to give importance/relevance to clinical associations. Once a clinical genetic or pharmacogenetic association is found, molecular studies can be utilized to explore the mechanism for the association. By employing cells in culture or transgenic mice modified with specific variant genes or sequence polymorphisms of interest, pathophysiological processes and response to pharmacological agents may be tested under conditions that are not approachable in human patients. These mechanistic studies may be particularly important when it comes to pharmacogenetic associations by providing significant, clinically relevant insights into the variable responses patients show to drug therapy.
Valley degree of freedom in topological metamaterials: from microwaves in meta-waveguides to nanoscale surface graphene plasmons (Conference Presentation)

Topological photonics enable us to design novel devices that exploit counter-intuitive propagation of electromagnetic waves. The key ingredient of topological photonics is a photonic topological insulator (PTI): a periodic structure that, in its bulk form, exhibits a propagation bandgap for a range of frequencies, yet supports localized edge states when interfaced with a different photonic structure exhibiting a bandgap for the same frequency range. Several types of PTIs emulating their respective condensed matter counterparts have already been proposed and experimentally demonstrated. One of the simplest PTIs exploits the valley degree of freedom in photonic crystals with a C_3 spatial symmetry. I will describe two examples of such structures: one designed and experimentally demonstrated at microwave frequencies and another designed for the mid-IR spectral range. We show that the microwave PTI structure, which is based on a metallic waveguide with an embedded array of specially designed metal rods, exhibits the previously unknown phenomenon of valley-protected “perfect” refraction: when interfaced with another waveguide, the edge states refract from the PTI metamaterial into the waveguide without any reflection. For the nanoscale topological metamaterial, we utilize graphene surface plasmons (GSPs) that propagate through a sheet of graphene with nano-patterned landscape of chemical potential. The chemical potential landscaping is achieved using an electrically biased metagate placed in close proximity of the graphene sheet. The advantage of this scheme is that the topological properties of the GSPs can be rapidly turned on and off, thus heralding the new era of active topological photonics on a nanoscale
Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.

Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Kruppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF4 regulates gene expression through transcriptional activation or repression via either DNA binding or protein-to-protein interactions, the outcome of KLF4-mediated regulation largely depends on the cellular context, cell cycle regulation, chromatin structure, and the presence of oncogenic drivers. This study first summarizes the current understanding of the regulation of self-renewal by KLF proteins in embryonic stem cells through a KLF circuitry and then delves into the potential function of KLF4 in normal hematopoietic stem cells and its emerging role in leukemia-initiating cells from pediatric patients with T-cell acute lymphoblastic leukemia via repression of the mitogen-activated protein kinase 7 pathway. Stem Cells Translational Medicine 2019;8:568-574.
Facts before Feelings: Theorizing Emotional Responses to Violent Trauma

What separates situations in which victims of violence become angry at the perpetrator from situations in which they do not? What characterizes the emotional response of victimized individuals who are not angry at the perpetrator? This paper use evidence from in-depth interviews with relatives of homicide victims in Chicago, IL to develop and illustrate a new theory of when and how individuals become angry in response to violence. Evidence suggests that cognitive clarity about the identity of the perpetrator, the perpetrator’s motive and the nature of the violence as unjust are necessary for an individual to become angry at the perpetrator. In addition to presenting a new theory, the paper also documents the emotional responses of individuals who are not angry at the perpetrator, and explores how certain contextual conditions—like the political narrative of conflict—might make it easier for victimized individuals to achieve cognitive clarity, become angry, and desire retribution.
Simulation of a financial market: The possibility of catastrophic disequilibrium

Abstract We use kinetic Monte Carlo simulations to produce solutions of an agent-based, rate equation model of an informationally efficient, closed financial market. The simulations produce a crash in the market that is forewarned through the observation of a market instability from which the market temporarily recovers. The market remained in a quasi-stable state for a relatively large amount of time between the warning and the crash, raising the prospect that some mitigating action can be taken in time to avert the impending crash. This result has strong ramifications for the future of predicting calamitous market events, especially if some observable aspect of financial markets can be positively identified and associated with simulation parameters.
Dancing Is Only Part of the Job: An Immersive Course in Dance Entrepreneurship

ABSTRACTThis article details my journey in teaching the college course Topics in Dance Entrepreneurship in the spring of 2017. The students, with my support, built a performing dance collective fro...
A Benchmark for Homomeric Enzyme Active Site Structure Prediction Highlights the Importance of Accurate Modeling of Protein Symmetry.

Accurate prediction and modeling of an enzyme’s active site are critical for engineering efforts as well as providing insight into an enzyme’s naturally occurring function. Previous efforts demonstrated that the integration of constraints enforcing strict geometric orientations between catalytic residues significantly improved the modeling accuracy for the active sites of monomeric enzymes. In this study, a similar approach was explored to evaluate the effect on the active sites of homomeric enzymes. A benchmark of 17 homomeric enzymes with known structures and a bound ligand relevant to the established chemistry were identified from the protein data bank. The enzymes identified span multiple classes as well as symmetries. Unlike what was observed for the monomeric enzymes, upon the application of catalytic geometric constraints, there was no significant improvement observed in modeling accuracy for either the active site of the protein structure or the accuracy of the subsequently docked ligand. Upon fur...
The nature of the chemical bonding in 5d transition-metal diatomic borides MB (M = Ir, Pt, Au)

Boron can form strong bonds with transition metals in diatomic metal borides (MB), but the nature of the chemical bonding has not been well understood. Recently, a quadruple bond was discovered in Rh≣B, consisting of two σ bonds formed between the Rh 4dz2 and B 2s/2p orbitals and two π bonds between the Rh 4dxz/4dyz and the B 2px/2py orbitals. The bonding between the 5d transition metals and boron is expected to be even stronger. Here, we report an investigation on the electronic structure and chemical bonding of the 5d transition metal diatomic borides (IrB, PtB, and AuB) using high-resolution photoelectron imaging on the corresponding anions (MB-) and theoretical calculations. Vibrationally resolved photoelectron spectra are obtained for all three anions, and the electron affinities are measured for IrB, PtB, and AuB to be 1.995(1), 2.153(3), and 0.877(6) eV, respectively. It is found that the weakly anti-bonding 3σ molecular orbital (mainly of M 6s and B sp characters) is singly occupied in IrB (3Δ) and PtB (2Σ+), resulting in a bond order of three and half for these two diatomic borides. The 3σ orbital is doubly occupied in AuB (1Σ+), giving rise to a weak triple bond. Despite the lower bond order, the bonding in IrB and PtB is only slightly weaker than that in RhB due to the more favorable interactions between the M 5d orbitals and the B sp orbitals.
Development of Flammable Dispersion Quantitative Property–Consequence Relationship Models Using Extreme Gradient Boosting

Uncontrolled release of flammable gases and liquids can lead to the formation of flammable vapor clouds. When their concentrations are above the lower flammable limit (LFL), or 1/2 LFL for conserva...
Nonstented Tubularized Incised Plate Distal Hypospadias Repair: A Single Center 5 Years' Experience

Abstract Objectives To report our immediate and delayed outcomes of non-stented tubularized incised plate (TIP) distal hypospadias repair. Methods We retrospectively reviewed all charts of children who underwent distal hypospadias repair in a single children's hospital from 2013 to 2018. Patients’ demographics, hypospadias characteristics, operative technique, and immediate and delayed outcomes were recorded. Results Of 280 consecutive distal hypospadias repairs that were identified, 74 were excluded due to the use of a repair other than TIP. Eleven stented TIP repairs were excluded as well. Of 195 non-stented repairs, immediate post-operative voiding complications were recorded in 11 (5.6%) and included multiple/ split stream in 6 (3%), dysuria and voiding difficulty in 2 (1%), urinary retention in 2 (1%), and gross hematuria that spontaneously resolved in 1 (0.5%). Late follow up was recorded in 142/195 (72.8%) repairs. Delayed urethroplasty/glansplasty complications were recorded in 12 (8.5%) and included urethrocutaneous fistula (UCF) in 10 (7.0%), meatal stenosis (MS) in 6 (4.2%) and glans/urethroplasty dehiscence (GD) in 2 (1.4%). Conclusion Avoiding post-operative urethral stents in distal hypospadias TIP repair reduces the morbidity associated with the stent and is a feasible option that carries acceptable immediate and delayed complication rates. Avoiding the stent eliminates stent-related bladder spasms, the need for other medications, and the short-term office visit for stent removal, therefore reducing parental anxiety, patient discomfort, and reducing cost.
Intersectionality in HCI: lost in translation

In this forum we explore different perspectives for how to apply intersectionality as a critical framework for design across multiple contexts. --- Yolanda A. Rankin and Jakita O. Thomas, Editors
Exploring Factors Associated With Morbidity and Mortality in Patients With Do-Not-Resuscitate Orders: A National Surgical Quality Improvement Program Database Analysis Within Surgical Groups.

Background Anesthesiologists caring for patients with do-not-resuscitate (DNR) orders may have ethical concerns because of their resuscitative wishes and may have clinical concerns because of their known increased risk of morbidity/mortality. Patient heterogeneity and/or emphasis on mortality outcomes make previous studies among patients with DNR orders difficult to interpret. We sought to explore factors associated with morbidity and mortality among patients with DNR orders, which were stratified by surgical subgroups. Methods Exploratory retrospective cohort study in adult patients undergoing prespecified colorectal, vascular, and orthopedic surgeries was performed using the American College of Surgeons National Surgical Quality Improvement Program Participant Use File data from 2010 to 2013. Among patients with preoperative DNR orders (ie, active DNR order written in the patient's chart before surgery), factors associated with 30-day mortality, increased length of stay, and inpatient death were determined via penalized regression. Unadjusted and adjusted estimates for selected variables are presented. Results After selection as above, 211,420 patients underwent prespecified procedures, and of those, 2755 (1.3%) had pre-existing DNR orders and met above selection to address morbidity/mortality aims. By specialty, of these patients with a preoperative DNR, 1149 underwent colorectal, 870 vascular, and 736 orthopedic surgery. Across groups, 36.2% were male and had a mean age 79.9 years (range 21-90). The 30-day mortality was 15.4%-27.2% and median length of stay was 6-12 days. Death at discharge was 7.0%, 13.1%, and 23.0% in orthopedics, vascular, and colorectal patients with a DNR, respectively. The strongest factors associated with increased odds of 30-day mortality were preoperative septic shock in colorectal patients, preoperative ascites in vascular patients, and any requirement of mechanical ventilation at admission in orthopedic patients. Conclusions In patients with DNR orders undergoing common surgical procedures, the association of characteristics with morbidity and mortality varies in both direction and magnitude. The DNR order itself should not be the defining measure of risk.
Morton's Metanarratives: Trope and Genre in Transformation I and Transformation II

The publication of Morton Horwitz’s brilliant 1977 study of early-Republic private legal doctrine, The Transformation of American Law: 1780–1860 (Transformation I), marked a significant turn in American legal history. Both within the legal academy and among historians more broadly, Transformation I was a lightning rod that divided orthodox legal thinkers and set the historical-legal agenda for the next decade. It fundamentally challenged received legal wisdom and tradition, as well as refuting the “consensus” historiography that had dominated the field following the Second World War. More importantly, it presaged a critical movement in American legal thought that would shake the academy to its foundations. Horwitz’s second history of American jurisprudence, The Transformation of American Law: 1870–1960 (Transformation II) was published in 1992 under very different intellectual circumstances. The critical movement that Horwitz had helped deliver was all but dead, and while Transformation II was generally well-received, it was not nearly the bombshell that the first iteration had been. In Horwitz’s own words, “it is a very different book.” Horwitz’s second text is no less erudite or technically skilled than his first, yet unquestionably something was different — either in the academy, with the reading public, or in the text itself — and any of these explanations might account for the book’s tepid reception. This paper is an attempt to understand that reception through an analysis of these possible explications.
Predicting the spatiotemporal exposure of aquatic species to intrusions of fire retardant in streams with limited data

Abstract Because fire retardant can enter streams and harm aquatic species including endangered fish, agencies such as the U.S. Forest Service (USFS) must estimate the downstream extent of toxic effects every time fire retardant enters streams (denoted as an “intrusion”). A challenge in estimating the length of stream affected by the intrusion and the exposure time of species in the affected reach is the lack of data typically available on the stream's geometry and flow characteristics. Previously, the USFS estimated the affected reach length assuming instantaneous mixing of the retardant over the reach; however, this approach neglects key river mixing processes. An approach is described that accounts for advection and dispersion of the retardant as well as the downstream growth of the stream. Applied to 13 intrusions documented by the USFS, the new approach shows affected reach lengths range between 8.0 and 362 km; all 13 cases exceeded previous estimates from an instantaneous mixing model. The time that a stationary individual in the affected reach is exposed to concentrations above a pre-defined toxicity threshold (10% of 96-hour LC50, for example) ranges from 0.17 to 2.73 h, with all but one case having a maximum exposure time less than 1.5 h. Results from 1152 hypothetical intrusions provided by the USFS confirm that exposure times rarely exceed 5 h. This result suggests that 96-hour tests to determine toxicity (LC50) to various species should be reconsidered. Although the approach described can be improved in several ways, it provides a first estimate of the effects of fire retardant intrusions.
Online Quiz as Exit Ticket: Using Technology to Reinforce Learning in Face to Face Classes.

Social work students are required to take research methods courses because research-informed practice and practice-informed research are essential to professional practice. However, these students ...
IRF5 Loss Impairs TLR9/BCR-Induced B Cell Activation, Proliferation and Plasmablast Differentiation through Erk1-Myc Signaling

Abstract Upon recognition of antigen, B cells undergo rapid proliferation followed by differentiation to specialized antibody secreting cells (ASCs). During this transition, B cells are reliant upon a multilayer transcription factor network to achieve a dramatic remodeling of the B cell transcriptional landscape. Increased levels of ASCs are seen in autoimmune diseases, such as sytemic lupus erythematosus (SLE), and certain B cell-associated malignancies. Studies suggest that altered expression of regulatory transcription factors play a role in the observed imbalance of B cell subsets in these diseases. The transcription factor interferon regulatory factor 5 (IRF5) is one such candidate as polymorphisms in IRF5 associate with risk of numerous autoimmune diseases and correlate with elevated IRF5 expression. Furthermore, dysregulated IRF5 expression and activation have been implicated in a variety of B cell lymphoproliferative disorders. It remains unclear, however, whether IRF5 has a role in normal B cell function. To date, little is known of IRF5 function in human B cells. We utilized human primary naive B cells combined with IRF5 knockdown to identify a critical new intrinsic role for IRF5 in B cell activation, proliferation and plasma cell differentiation. IRF5 knockdown resulted in significant IgD retention, reduced proliferation, plasmablast differentiation, and IgG secretion. The observed decreases were due to impaired B cell activation and clonal expansion. Distinct from murine studies, we identify and confirm new IRF5 target genes, IRF4, ERK1, and MYC, and signaling pathways that mediate IRF5 B cell-intrinsic function. Together, these results identify IRF5 as an early regulator of human B cell activation and provide the first dataset in human primary B cells to map IRF5 dysfunction in disease. Disclosures No relevant conflicts of interest to declare.
Do Minimally Invasive Benign Prostatic Hyperplasia Treatments Preserve Sexual Function? A Contemporary Review of the Literature.

PURPOSE OF REVIEW The aim of this study is to compare the sexual function outcomes related to minimally invasive surgical therapies (MISTs) (UroLift®, Rezum™, Aquablation®, prostate artery embolization, and iTind®) for the treatment of benign prostatic hyperplasia (BPH). RECENT FINDINGS Clinical trials and retrospective data evaluating MISTs for BPH have demonstrated improved or stable sexual function outcomes when compared to sham control or transurethral resection of the prostate. Outcomes were assessed at baseline and following treatments using patient-reported outcome measures. Rezum and Aquablation demonstrated preservation of overall ejaculatory function and erectile function at 36-month follow-up. Similar outcomes occurred with UroLift after a 60-month follow-up. Erectile function was preserved following prostate artery embolization and iTIND up to 12 months. MIST for the management of BPH has been demonstrated to be effective in improving urinary function and appears to minimize potential collateral damage on sexual function following treatment.
Day of the Dead in the USA: The Migration and Transformation of a Cultural Phenomenon

Honoring relatives by tending graves, building altars, and cooking festive meals has been an honored tradition among Latin Americans for centuries. The tribute, "el Dia de los Muertos," has enjoyed renewed popularity since the 1970s when Latino activists and artists in the United States began expanding "Day of the Dead" north of the border with celebrations of performance art, Aztec danza, art exhibits, and other public expressions. Focusing on the power of ritual to serve as a communication medium, Regina M. Marchi combines a mix of ethnography, historical research, oral history, and critical cultural analysis to explore the manifold and unexpected transformations that occur when the tradition is embraced by the mainstream. A testament to the complex nature of ethnic identity, "Day of the Dead in the USA" provides insight into the power of ritual to create community, transmit oppositional messages, and advance educational, political, and economic goals.
Gene expression profile-based predictors of response to chemotherapy

A molecular test that could help in selecting the most effective chemotherapy for a particular individual could save patients from unnecessary toxicity, and the right choice of drugs may save lives, particularly in the adjuvant treatment of breast cancer. Administration of chemotherapy before surgery provides an attractive opportunity to discover predictors of response [1]. Pathologic complete eradication of cancer from the breast and lymph nodes (pCR) represents an extreme form of chemotherapy sensitivity and invariably heralds excellent long-term survival. We adopted pCR as an early surrogate of clinically meaningful benefit from therapy and as an outcome that is worth predicting. There are simple clinical and histological parameters, including grade, estrogen receptor status and tumor size, that can be combined into powerful prediction scores. However, these clinical variables do not yield treatment regimen specific predictions, and they cannot be used to select one therapy over another. Assessment of traditional single gene markers of chemotherapy sensitivity has not yet resulted in clinically useful tests. Gene expression profiling, which enables simultaneous measurement of thousands of genes, represents a promising new tool that may be applied to this clinical problem. It is currently unknown what the best strategy is to discover response predictors from high dimensional gene expression data. The simplest approach may be to search for the single most informative gene that is differentially expressed between responders and nonresponders. This may lead to new mechanistic insights into the biology of chemotherapy response and could yield easy-to-use but moderately powerful single gene predictive markers [2]. Another approach is to identify gene expression signatures that are predictive of response, assuming that the combined information provided by multiple genes would result in more accurate predictions than any single gene can do. Several small studies have suggested that this is feasible [3]. Large-scale validation of these results is needed and is currently underway. Yet another approach is to recognize the different molecular subtypes of breast cancer and attempt to develop distinct predictors for each subtype [4]. This approach assumes that, by focusing on the molecularly more homogenous subgroups, more accurate predictors could be developed than by analyzing all breast cancers together. We shall present results from our own research program, illustrating the successes and limitations of each of these approaches.
Disc Immuno-Immobilization Method for Simultaneous Typing and Isolation of Salmonella Flagellar Phases

Salmonella organisms of an unknown serotype are inoculated in the center of a motility agar plate, and paper discs impregnated with antiflagellar antisera are placed in the periphery of the plate. The plate is incubated at room temperature overnight. During this time, the bacteria spread in a widening circle toward the discs, while the antiserum from each disc, in turn, diffuses centrifugally. When the motile organisms encounter an antiserum reacting with their flagella, they are immobilized. A semicircular line of immobilization is noted around the reactive antiserum disc. Eleven different Salmonella isolates were typed in duplicate by a standard method and by the immuno-immobilization method. Results obtained by the two methods were essentially identical. Simultaneously, single phases were isolated from the zone between the immobilization line and its antiserum disc. Isolates from this region were of the phase not immobilized by the antiserum disc. The dried discs, prepared in tris(hydroxymethyl)aminomethane buffer and stored at 4 C, were stable for at least 5 months. The method can be used for the study of relatedness of surface antigens of motile, growing bacteria, thus circumventing the need for solubilization of these antigens. The results obtained can be interpreted in a similar fashion to the “identity”-“nonidentity” lines of the Ochterlony double-diffusion technique for soluble antigens. Images
PERMUTATIONS AS PRODUCT OF PARALLEL TRANSPOSITIONS

† Abstract. It was conjectured that a permutation matrix with bandwidth b can be written as a product of no more than 2b − 1 permutation matrices of bandwidth 1. In this note, two proofs are given to affirm the conjecture.
Comments on Refereeing

On the basis of 29 years of editorial experience, I suggest ways of confronting refereeing problems that seem fair to the authors, and that produce efficiently a reliable and clear publication. The purposes for reviewing manuscripts and the need to do so are given. The advantages and disadvantages of the two refereeing systems (parallel and series) are presented. Policies for selecting referees, their qualifications, how long to wait for reports, how to handle controversial manuscripts, and whether the referees should be open or anonymous are explained.