cssi/SciSciGPT-SciSciNet huggingface dataset:
Efficacy of pharmacologic glucagon in acute experimental pancreatitis.

• Microcirculatory derangements in the pancreas associated with acute pancreatitis may contribute to a low-flow state and lead to pancreatic necrosis. This study investigated the effects of glucagon, a selective mesenteric arterial dilator, on pancreatic ischemia in canine bile-trypsin-induced pancreatitis (BTP). Measurements of cardiac index (CI), total pancreatic blood flow (Q P ), pancreatic oxygen consumption (O 2 C P ), and pancreatic arteriovenous shunt flow (Q AVS ) were obtained prior to and after inducing BTP. Bile-trypsin-induced pancreatitis was induced in 18 dogs. Nine received lactated Ringer's solution alone (LRPAN) at 6.5 mL/kg/hr, nine received lactated Ringer's solution plus continuous intravenous (IV) glucagon hydrochloride (GLUPAN) at 1.0 μg/kg/min, and nine undergoing periportal dissection without BTP received IV glucagon (GLUCON). Following BTP, CI, Q P , and O 2 C P decreased significantly and Q AVS remained unchanged in crystalloid-treated animals (LRPAN). Glucagon administration (GLUPAN) transiently increased CI and Q P but failed to improve O 2 C P and did not change Q AVS . The decrease in O 2 C P observed after BTP in association with a constant Q AVS suggests a metabolic block to oxygen uptake at the cellular level. Glucagon in pharmacologic doses does not reverse abnormalities in O 2 C P and is therefore of questionable physiologic benefit in the treatment of acute pancreatitis. ( Arch Surg 1985;120:355-360)
Arsenic repartitioning during biogenic sulfidization and transformation of ferrihydrite.

Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)–ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II)(aq) concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III)(s) depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.
Software reliability model selection

No one software reliability growth model has ever been shown to work well in all circumstances. This paper presents our evaluation results for two case studies in which the Akaike information criterion (AIC) was used. The AIC not only selects the best model among several reliability models, but also possess favourable properties that practitioners like to see in their software reliability modelling practices. These properties include simplicity, accuracy and ease of application. We propose using the Akaike information criterion to select the best model for each software system.
Fear influences perceived reaching to targets in audition, but not vision

Abstract The superordinate mechanism view of emotions predicts that fear should influence perception to carry out the evolved function of overcoming immediate threats. Previous work demonstrates that fear does adaptively influence visual perception. However, there are recurring situations in which auditory perception is used for overcoming immediate threats (e.g., avoiding predators after dark). Some research suggests that the auditory system, independent of fear, is adaptively biased to hear approaching sounds as closer than equidistant receding sounds (a.k.a. the looming bias). The present study investigated whether fear, as a superordinate mechanism, influences auditory perception such that sounds are perceived to be closer, ultimately providing an advantage when avoiding immediate threats. Participants judged whether or not they could reach to an aurally or visually perceived target while either in a fearful or neutral state. The results demonstrated that while in a fearful state, participants judged targets to be closer to them, but only when the target was perceived aurally. This finding extends previous work on adaptive biases in auditory perception to include the influence of fear.
Neurogenic bladder: etiology and assessment

A review of the various causes of neurologic impairment to the lower urinary tract in children was the aim of this presentation. The emphasis was on diagnosis, pathophysiology, and treatment that strive to maintain as normal a function as possible in order to achieve eventual urinary continence and health of the upper urinary tract. The latest principles based on the most up to date evidence are promulgated but with an eye towards historical prospective. The reader should gain an adequate understanding of various disorders that comprise this condition and feel comfortable with proposing options for management when faced with the responsibility of caring for an affected child.
Measurements of semileptonic branching fractions of B mesons at the Upsilon (4S) resonance

We report new measurements of semileptonic branching fractions of $B$ mesons produced at the $\ensuremath{\Upsilon}(4S)$ resonance determined by fitting the inclusive electron and muon momentum spectra to different theoretical models. Using $B(\overline{B}\ensuremath{\rightarrow}X{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}})$ to denote the average of the semileptonic branching fractions for $B$ decay to electrons and muons, we obtain $B(\overline{B}\ensuremath{\rightarrow}X{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}})=(10.5\ifmmode\pm\else\textpm\fi{}0.2\ifmmode\pm\else\textpm\fi{}0.4)%$ using the refined free-quark model of Altarelli et al., and $B(\overline{B}\ensuremath{\rightarrow}X{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}})=(11.2\ifmmode\pm\else\textpm\fi{}0.3\ifmmode\pm\else\textpm\fi{}0.4)%$ using a modified version of the form-factor model of Isgur et al., in which the ${D}^{**}{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}}$ contribution is allowed to float in the fit. The average of these two results is $B(\overline{B}\ensuremath{\rightarrow}X{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}})=(10.8\ifmmode\pm\else\textpm\fi{}0.2\ifmmode\pm\else\textpm\fi{}0.4\ifmmode\pm\else\textpm\fi{}0.4)%$, where the errors are statistical, systematic uncertainties in the measurement, and systematic uncertainties associated with the theoretical models, respectively. Semileptonic branching fractions as low as this are difficult to accommodate in theoretical models where hadronic $B$-meson decays arise only from spectator diagrams. We use dilepton yields to limit the uncertainty in the semileptonic branching fraction due to the possible existence of non-$B\overline{B}$ decays of the $\ensuremath{\Upsilon}(4S)$. In addition, we tag neutral $B$ mesons using the decays ${\overline{B}}^{0}\ensuremath{\rightarrow}{D}^{*+}{\ensuremath{\pi}}^{\ensuremath{-}}$ and ${\overline{B}}^{0}\ensuremath{\rightarrow}{D}^{*+}{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}}$ to obtain the first direct measurement of semileptonic branching fractions for neutral $B$ mesons; the average of the electron and muon results for neutral $B$ mesons is $B({\overline{B}}^{0}\ensuremath{\rightarrow}X{\ensuremath{\ell}}^{\ensuremath{-}}\overline{\ensuremath{\nu}})=(9.9\ifmmode\pm\else\textpm\fi{}3.0\ifmmode\pm\else\textpm\fi{}0.9)%$.
Incremental diagnostic yield of chromoendoscopy and outcomes in inflammatory bowel disease patients with a history of colorectal dysplasia on white-light endoscopy.

Background and Aims Chromoendoscopy (CE) identifies dysplastic lesions with a higher sensitivity than white-light endoscopy (WLE). The role of CE in the management of dysplasia on surveillance WLE in inflammatory bowel disease (IBD) remains unclear. Methods A retrospective cohort of IBD patients with colorectal dysplasia on WLE who subsequently underwent CE between January 1, 2006 and August 31, 2013 was identified. Endoscopic and histologic findings were compared among the index WLE, first CE, and subsequent CE. Outcomes assessed included endoscopic lesion removal, surgery or repeat CE, and diagnosis of colorectal cancer. Results Ninety-five index cases were identified. The median duration of IBD was 18 years (interquartile range 9.3-29.8); 78 patients had ulcerative colitis. Dysplasia was identified in 55 patients during the index WLE with targeted biopsies of 72 lesions. The first CE visualized dysplastic lesions in 50 patients, including 34 new lesions (not visualized on the index examination). Endoscopic resection was performed successfully of 43 lesions, most in the cecum/ascending colon (n = 20) with sessile morphology (n = 33). After the first CE, 14 patients underwent surgery that revealed 2 cases of colorectal cancer and 3 cases of high-grade dysplasia. Multiple CEs were performed in 44 patients. Of these, 20 patients had 34 visualized lesions, 26 of which were new findings. Conclusion Initial and subsequent CE performed in IBD patients with a history of colorectal dysplasia on WLE frequently identified new lesions, most of which were amenable to endoscopic treatment. These data support the use of serial CEs in this high-risk population.
Effect on Drosophila melanogaster and S-37 Tumor Cells; Postulates for Magnetic Field Interactions

Since ancient times man seems to have been fascinated by the mysterious powers of a magnetic field over life, but a true scientific interest in the study of its effects on living matter was not aroused until the nineteenth century. Since then, several reports on the effects of magnetic fields on life from bacteria to man have appeared from time to time. In the last decade this interest has intensified and several studies have been published in many journals.
Thermal diffusion boron doping of single-crystal natural diamond

With the best overall electronic and thermal properties, single crystal diamond (SCD) is the extreme wide bandgap material that is expected to revolutionize power electronics and radio-frequency electronics in the future. However, turning SCD into useful semiconductors requires overcoming doping challenges, as conventional substitutional doping techniques, such as thermal diffusion and ion implantation, are not easily applicable to SCD. Here we report a simple and easily accessible doping strategy demonstrating that electrically activated, substitutional doping in SCD without inducing graphitization transition or lattice damage can be readily realized with thermal diffusion at relatively low temperatures by using heavily doped Si nanomembranes as a unique dopant carrying medium. Atomistic simulations elucidate a vacancy exchange boron doping mechanism that occurs at the bonded interface between Si and diamond. We further demonstrate selectively doped high voltage diodes and half-wave rectifier circuits using such doped SCD. Our new doping strategy has established a reachable path toward using SCDs for future high voltage power conversion systems and for other novel diamond based electronic devices. The novel doping mechanism may find its critical use in other wide bandgap semiconductors.
Tale of Two Books

Article discusses the basics of treating moldy books and illustrates with photos the steps used by the staff at the E. Lingle Craig Preservation Lab for handling such items when they are received.
The molecular architecture of disease

Many human diseases have strong genetic components, as evidenced by their familial occurrence. Genome wide association approaches, following the guidance of the common disease/common variant hypothesis have largely failed to explain known heritabilities. In contrast, the discovery of single highly penetrant alleles has provided convincing explanation for many rare human disorders. We are now extending the search for the involvement of rare alleles in common disease by systematically analysing individuals with sporadic disease in cohorts where familial cases are well understood. With available cohorts we see excess ‘carrier burden’ within single individuals in some diseases, provided we condition the analyses on known gene groups. Extension of these studies to provide genome-wide significance is the possible bridge between the architecture of the rare monogenic disorders and complex disease.
A Critical Analysis of Recent Literature Dealing with Marketing Efficiency

IN VIEW of the title of this paper, it may sound facetious if I suggest that there is practically no recent literature dealing with marketing efficiency. Yet, if my interpretation of the word "efficiency" is correct, then my statement is true. Exactly what is efficiency in marketing? Professor Slichter tells us that efficiency "relates simply to the ratio of results achieved to the means used,"' the implication being that marketing is most efficient when it achieves the greatest results from given means-or, perhaps better put, when it achieves the maximum results per unit of means. But of course, Professor Slichter's definition is of little value to us until we develop a measure of the "results achieved" by marketing as well as the "means used," as it is only by comparing results with means that efficiency is measured. Now what are the results that marketing seeks to achieve? If it does not sound entirely too elementary, I would like to suggest that marketing-as does the field of which it is a part, that is, economics-seeks to satisfy human wants.2 And what are the means of attaining this desired result? Once again we must go back to Chapter I of practically any elementary book on economics and recall that the means consist of land, labor, capital, and management-or, more
All-ceramic full-coverage restorations: concepts and guidelines for material selection.

UNLABELLED High-strength, all-ceramic systems for full-coverage restorations use all-ceramic core materials for the fabrication and processing of infrastructures (eg, crown copings, fixed partial denture frameworks) that are then veneered with porcelain. Not all of these all-ceramic core materials are alike, and as such, they present with different properties that may affect their indications and limitations, the laboratory procedures used for their processing, and their clinical handling. This article reviews their clinically relevant properties and discusses the effect of these characteristics on their indications and recommended clinical procedures. LEARNING OBJECTIVES This article provides an overview of the clinically relevant properties of high-strength, all-ceramic systems used for aesthetic restorative dentistry. Upon reading this article, the reader should: Be able to differentiate among the principal all-ceramic material systems. Understand the clinical indications for contemporary, high-strength ceramics.
NCCN Guidelines Updates: Breast Cancer

The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor-positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy. Most of the benefit is modest and toxicity is an issue; therefore, extended-duration endocrine therapy should be highly individualized. For triple-negative disease, platinum agents and PARP inhibitors are helping some patients, but immunotherapies and other novel classes of drugs now in development hold the promise of even better outcomes. In HER2-positive early-stage disease, dual HER2 blockade is of modest benefit, and extended treatment with neratinib may be a good option for some high-risk patients.
Targeting AKT Signaling in Pediatric Acute Lymphoblastic Leukemia with Sulforaphane

Abstract 1521 Refractory and relapse acute lymphoblastic leukemia (ALL) is one of the leading causes of cancer-related death in children. Novel agents are still in need as a frontline therapy in high risk patients and salvage agent in relapse patients. Leukemic cells acquire a survival advantage over normal blood cells by losing control of the cell cycle and activating pro-survival signals. There are emerging evidences showing that the PI3K/AKT/mTOR pathway is frequently activated in both T cell acute lymphoblastic leukemia (T-ALL) and precursor B cell acute lymphoblastic leukemia (pre-B ALL) (approximately 30% of ALL patients). Thus, drugs able to inhibit AKT signaling are potential candidates for ALL treatment. Sulforaphane (SF) is a dietary compound found in cruciferous vegetables with well-known chemopreventive and chemotherapeutic function in solid tumors by inducing apoptosis and inhibiting survival and cell division. However, the anti-leukemic capacity of SF in hematologic malignancies has not been extensively investigated. In this study, we found increased cleavage of PARP, caspase-3, caspase-8 and caspase-9 by immunoblots in pre-B and T-ALL cell lines treated with SF (5–10 μM) for 24 –48 hours. In addition, we detected increased expression of p21 and cyclin B that correlated with a G2/M block and DNA damage observed in SF treated cells by analysis of DNA content and H2AXγ expression. Noteworthy, SF-treated pre-B and T-ALL cell lines exhibit lower levels of total and phosphorylated AKT in addition to decreased levels of total and phosphorylated mTOR, which was independent of p53 and PTEN activities. Lower survival signals upon SF treatment correlated with a dose- and time-dependent cytotoxicity in pre-B ALL cell lines (Nalm-6, REH and RS-4) and T-ALL cell lines (Jurkat, RPMI, DND-41 and KOPTK1) compared to EBV-transformed lymphoblasts used as a control. Interestingly, SF showed a synergistic effect with vincristine in pre-B and T-ALL cell lines, suggesting a potential use of SF in adjunctive therapy. Aiming to support future clinical trials, we confirmed that SF is effective in lymphoblasts from pediatric patients suffering with ALL, both pre-B and T, in a time- and dose-dependent manner (95% confidence interval IC50: pre-B ALL = 9.9 – 12.13 μM, T-ALL = 8.3 –11.00 μM). To investigate whether SF is effective in vivo in a xenograft mouse model, we injected nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice with Nalm-6 cells transduced with GFP-FFluc for bioluminescent imaging detection. SF treatment (2 mg i.p. daily) significantly reduced tumor burden compared to the control group (injected with vehicle). Collectively, our data show that SF has anti-leukemic properties in ALL, both in primary samples from patients and cell lines, by inducing cell death selectively in leukemic cells likely by inhibiting AKT-dependent survival signals. Disclosures: No relevant conflicts of interest to declare.
Picosecond Pulsed Laser-Induced Melting and Glass Formation in Metals

Abstract Irradiation of a solid surface by a picosecond laser pulse leads to melting of a thin overlay, and subsequent quenching at rates of 1012K/s or higher. This technique is also one of the few available for superheating a crystal above its melting temperature. The ultra-fast quenching rates permit the formation of new metallic glasses. Work on the Fe-B and Ni-Nb system is reviewed, and new results on the Mo-Ni, Mo-Co and Nb-Co systems are reported. In all cases, glasses are formed below the To-line, indicating that partitionless crystallization is usually at least partially diffusion controlled due to the change in short range order upon crystallization; only in the simplest structures, such as disordered f.c.c, solutions, are the partitionless crystallization kinetics fast enough to preclude glass formation.
The Editions Of Jacques-Auguste De Thou’s History Of His Time

Any would-be editor of Jacques-Auguste de Thou’s major work, the History of His Time, must solve two problems if he is to give an accurate text to his readers: first, the printing history of the different editions of the History must be determined and second, the relationship of those editions to de Thou’s manuscripts must be analyzed. The second of these problems requires investigating also the traditions which assert that certain copies of the History, now in libraries both in Europe and America, contain manuscript annotations in de Thou’s hand or in those of his personal secretaries. These two problems form the subject-matter of the first part of this book.
Under Abbasids and Successor States

The displacement of the Umayyads by Abbasids in 750 was more than a routinely dynastic change; it marked the termination of a whole era in Islamic history and the commencement of another. In the new era the hegemony of Syria ended and that of Iraq began. The glory of Damascus faded before that of Baghdad. Muawiyah and his successors counted on the loyalty of Syrians — still predominantly Christians —, abu-al-Abbas and his successors on Iraqi-Persian loyalty. The centre of Islamic gravity, first in Hijaz, shifted northward and now to the east. The model was no more Byzantine; it became Persian. Gradually the old Arabian aristocracy based on blood and sword was replaced by one of Neo-Moslems of Turkish, Persian and other ethnic origins based on a society in which trade, industry and business played for the first time a role.
The evolving utility of diffusion tensor tractography in the surgical management of temporal lobe epilepsy: a review.

Diffusion tensor imaging (DTI) is a relatively new imaging modality that has found many peri-operative applications in neurosurgery. A comprehensive survey of the applications of diffusion tensor imaging (DTI) in planning for temporal lobe epilepsy surgery was conducted. The presentation of this literature is supplemented by a case illustration. The authors have found that DTI is well utilized in epilepsy surgery, primarily in the tractography of Meyer’s loop. DTI has also been used to demonstrate extratemporal connections that may be responsible for surgical failure as well as perioperative planning. The tractographic anatomy of the temporal lobe is discussed and presented with original DTI pictures. The uses of DTI in epilepsy surgery are varied and rapidly evolving. A discussion of the technology, its limitations, and its applications is well warranted and presented in this article.
A Land Use Map of Uganda

(1959). A Land Use Map of Uganda. The East African Agricultural Journal: Vol. 25, No. 1, pp. 50-52.
Abstract 107: Impaired Lipid Metabolism and Enhanced Atherosclerosis in Clock Mutant Mice

Clock is a key transcription factor that controls circadian regulation. Here, we show that dominant-negative Clock mutant protein (Clock Δ19/Δ19 ) enhances hyperlipidemia and atherosclerosis in Apoe -/- mice. Clk [[Unable to Display Character: ∆]]19/[[Unable to Display Character: ∆]]19 Apoe -/- mice display hypercholesterolemia, show enhanced cholesterol absorption and express more NPC1L1, ACAT2 and MTP in the intestine. Macrophages from Clk [[Unable to Display Character: ∆]]19/[[Unable to Display Character: ∆]]19 Apoe -/- mice express high levels of scavenger receptors and take up more modified lipoproteins compared to Apoe -/- mice; but they express low levels of ABCA1 and are defective in cholesterol efflux. Molecular studies reveal that Clock regulates ABCA1 expression in macrophages by modulating USF2 expression. Thus, Clock Δ19/Δ19 protein enhances atherosclerosis by increasing intestinal cholesterol absorption by enterocytes, augmenting uptake of modified lipoproteins by macrophages and reducing cholesterol efflux from macrophages. These studies establish that circadian Clock plays a pivotal role in the regulation of cholesterol metabolism and atherosclerosis.
ASP-DAC 2017 keynote speech I: In memory of Edward J. McCluskey: The next wave of pioneering innovations

This special plenary session will celebrate Prof. McCluskey (who passed away in 2016) through three keynote speeches by world-renowned scholars on the next wave of pioneering innovations, starting with a memorial speech by Prof. Jacob Abraham of University of Texas at Austin.
Evaluation of Out-of-Plane Sensitivity and Artifacts in Photoacoustic Imaging

Photoacoustic Imaging (PAI) systems are rapidly emerging biomedical diagnostic devices. We investigated PAI out-of-plane artifacts using biorealistic tissue phantoms, which can support device optimization, clinical translation, and inter-comparison.
A Low-Cost Time-Resolved Spectrometer for the Study of Ruby Emission

A low-cost time-resolved emission spectrometer optimized for ruby emission is presented. The use of a Class II diode laser module as the excitation source reduces costs and hazards. The design presented here can facilitate the inclusion of time-resolved emission spectroscopy with laser excitation sources in the undergraduate laboratory curriculum. The ruby decay data show evidence of radiation trapping, an interesting optical phenomenon discussed in the research literature.
Stress Accounts for the Association Between ADHD Symptoms and Suicide Ideation When Stress-Reactive Rumination Is High

ADHD symptoms are significantly associated with suicide ideation. However, the variables that explain this association remain unknown. This study tested a theoretical model in which stress was hypothesized to account for the association between ADHD symptoms and suicide ideation among individuals high, but not low, in ruminative responding to stress. We examined this model in a sample of 432 emerging adults, who were predominantly female (72.5%) and Hispanic (70.6%), with a mean age of 19.73 years. Demographic and clinical (ADHD symptoms, stress, stress-reactive rumination, depressive symptoms) information was collected via self-reported rating scales. ADHD symptoms were significantly and positively associated with stress, stress-reactive rumination, and suicide ideation. As hypothesized, the association between ADHD symptoms and suicide ideation was accounted for by stress, and this effect was strongest at high levels of stress-reactive rumination. Conclusions did not change after controlling for depressive symptoms. These findings shed light on one explanation of the elevated levels of suicide ideation seen in emerging adults with elevated ADHD symptoms: heightened levels of stressful events and a tendency to respond to stress by ruminating. Implications for theory development and prevention efforts are discussed.
Actual and Perceived Questions Asked by Preceptors with and Without the Use of Bug-in-Ear Technology

Context: Questioning is an instructional strategy used by preceptors to assess knowledge and improve clinical reasoning in students. Preceptors face challenges asking high-level questions, and bug-...
Beyond Usefulness: A Fitness-Utility Model for DSR

Current thinking in design science research (DSR) defines utility as the primary research goal (e.g. [1, p. 80]). In this context, the close relationship of utility to practical usefulness is emphasized. With a goal to increase the impacts of DSR, the search for the dependent variable in DSR requires some rethinking. A pair of alternative dependent variables can be considered: design fitness and design utility. In the case of fitness, we focus on its biological meaning—the ability of an entity to reproduce itself and evolve from generation to generation. In the case of utility, rather than viewing it as being roughly equivalent to usefulness, we focus on its meaning in fields such as economics and decision sciences, where it serves as the basis for ranking decision alternatives. Naturally, usefulness plays an important role in determining both fitness and utility. Neither of these variables, however, is solely determined by usefulness. Indeed, we believe that understanding the relationship between the three variables via a new fitness-utility model complements current thinking and provides important insights into the nature of design science.
Topoisomerase II Inhibitors: Chemical Biology

DNA topoisomerase II (Top2) is the target of a chemically diverse set of compounds with substantial antitumor activity. Agents such as doxorubicin and etoposide are FDA approved for the treatment of both leukemias and solid tumors. Most clinically active drugs targeting Top2 lead to elevated levels of covalent Top2-cleaved DNA complexes and exert their antitumor effect through enzyme-mediated DNA damage. Drugs targeting Top2 are accompanied by substantial toxicities including cardiomyopathy following treatment with anthracyclines, and the generation of secondary leukemias. Biochemical and structural studies have illuminated many aspects of the action of drugs targeting topoisomerase II, although the precise molecular details of enzyme inhibition remain poorly understood. This chapter surveys some of the approved agents that target topoisomerase II, as well as some of the newer compounds that may have clinical promise. Although currently used Top2 targeting drugs act by generating enzyme-mediated DNA damage, catalytic inhibition remains a tantalizing possibility. Since current results suggest that topoisomerase IIβ, one of the two mammalian isoforms of topoisomerase II, is important for some of the deleterious effects of Top2 agents, the possibility of isoform-specific inhibitors is also considered.
Exploration of copper-free ZnTe buffer layers for CdTe-based solar cells

Development of copper-free ZnTe buffer layers for CdTe-based solar cells is an important avenue for improving stability. Group V elements offer a path towards that goal. This work explores two group V elements, phosphorous and antimony, as candidates for making copper-free p-type ZnTe buffer layer using thermal evaporation. It is found that incorporation of both elements into ZnTe film can easily be done. In addition, as deposited ZnTe films are Te-rich and Cd 1-x Zn x Te alloys form upon co-evaporation of ZnTe and Cd 3 P 2 , improving crystallinity and stoichiometry of the film. Activation of P poses a challenge, while ZnTe films with Sb produced good sheet resistance values.
Deformation behavior of core–shell nanowire structures with coherent and semi-coherent interfaces

The mechanical properties of core–shell bimetallic composite nanowires, forming the bases of nanoporous metallic foams, have been investigated and compared with pure metal nanowires using molecular dynamics simulations. In the current study, pure copper and gold nanowires under uniaxial loading were tested at room temperature and compared to composite nanowires of the same materials (core) with a nickel coating (shell). The core radius ranged from 1 to 15 nm, and the shell thickness ranged from 0.1 to 5 nm. The tension strain was performed along the [001] direction under room temperature. Both coherent and semi-coherent composite nanowires were studied, and the effect of coating layer thickness was investigated. The strengthening mechanisms of the core–shell structures due to the presence of the two different types of interfaces were investigated for various nickel thicknesses. The atomistic simulation results revealed that the addition of the nickel shell strengthens the structure when the layer thickness exceeds a critical value.
Merging the Pathophysiology and Pharmacotherapy of Tics

Background: Anatomically, cortical-basal ganglia-thalamo-cortical (CBGTC) circuits have an essential role in the expression of tics. At the biochemical level, the proper conveyance of messages through these circuits requires several functionally integrated neurotransmitter systems. In this manuscript, evidence supporting proposed pathophysiological abnormalities, both anatomical and chemical is reviewed. In addition, the results of standard and emerging tic-suppressing therapies affecting nine separate neurotransmitter systems are discussed. The goal of this review is to integrate our current understanding of the pathophysiology of Tourette syndrome (TS) with present and proposed pharmacotherapies for tic suppression. Methods: For this manuscript, literature searches were conducted for both current basic science and clinical information in PubMed, Google-Scholar, and other scholarly journals to September 2018. Results: The precise primary site of abnormality for tics remains undetermined. Although many pathophysiologic hypotheses favor a specific abnormality of the cortex, striatum, or globus pallidus, others recognize essential influences from regions such as the thalamus, cerebellum, brainstem, and ventral striatum. Some prefer an alteration within direct and indirect pathways, whereas others believe this fails to recognize the multiple interactions within and between CBGTC circuits. Although research and clinical evidence supports involvement of the dopaminergic system, additional data emphasizes the potential roles for several other neurotransmitter systems. Discussion: A greater understanding of the primary neurochemical defect in TS would be extremely valuable for the development of new tic-suppressing therapies. Nevertheless, recognizing the varied and complex interactions that exist in a multi-neurotransmitter system, successful therapy may not require direct targeting of the primary abnormality.
Challenges With the Development of Biomaterials for Sustainable Tissue Engineering

The field of tissue engineering has tantalizingly offered the possibility of regenerating new tissue in order to treat a multitude of diseases and conditions within the human body. Nevertheless, in spite of significant progress with in vitro and small animal studies, progress towards realizing the clinical and commercial endpoints has been slow and many would argue that ultimate goals, especially in treating those conditions which, as yet, do not have acceptable conventional therapies, may never be reached because of flawed scientific rationale. In other words, sustainable tissue engineering may not be achievable with current approaches. One of the major factors here is the choice of biomaterial that is intended, through its use as a ‘scaffold’, to guide the regeneration process. For many years, effective specifications for these biomaterials have not been well-articulated, and the requirements for biodegradability and prior FDA approval for use in medical devices, have dominated material selection processes. This essay argues that these considerations are not only wrong in principle but counter-productive in practice. Materials, such as many synthetic bioabsorbable polymers, which are designed to have no biological activity that could stimulate target cells to express new and appropriate tissue, will not be effective. It is argued here that a traditional ‘scaffold’ represents the wrong approach, and that tissue-engineering templates that are designed to replicate the niche, or microenvironment, of these target cells are much more likely to succeed.
Exploring Institutional Processes in a District-Wide Dual Language Program: Who is it for? Who is Left Out?

As the number of dual language programs in the U.S. is on the rise, district and school administrators need to pay attention to race as they design and implement these programs to offer equitable a...
Racial and Ethnic Differences in Parental Decision-Making Roles in Pediatric Oncology.

Background: Prior work in adult oncology suggests minority patients are less involved in decision making than preferred. However, few studies have explored decision-making experiences of minority p...
EU Mediation in Montenegro: Satisficing, Formulation and Manipulation in International Mediation

This chapter investigates the negotiations on Montenegro’s independence in 2006. The author shows that many of the voting thresholds proposed by the two camps (unionists and pro-independents) during their negotiations about the independence referendum were salient or focal. Arguing that focal point solutions are often suboptimal to both parties, he demonstrates that they offer important opportunities to mediators. Focal points can induce the parties toward the adoption of a satisficing rather than a maximizing strategy conductive to the reaching of an agreement that both parties can live with. This is the case even when the mediators are neither unbiased nor indifferent to the outcome of the negotiations.
Patterns of the COVID19 epidemic spread around the world: exponential vs power laws

Abstract We have analyzed the COVID19 epidemic data of more than 174 countries (excluding China) in the period between January 22 and March 28, 2020. We found that some countries (such as the US, the UK, and Canada) follow an exponential epidemic growth, while others (like Italy and several other European countries) show a power law like growth. At the same time, regardless of the best fitting law, most countries can be shown to follow a trajectory similar to that of Italy, but with varying degrees of delay. We found that countries with “younger” epidemics tend to exhibit more exponential like behavior, while countries that are closer behind Italy tend to follow a power law growth. We hypothesize that there is a universal growth pattern of this infection that starts off as exponential and subsequently becomes more power law like. Although it cannot be excluded that this growth pattern is a consequence of social distancing measures, an alternative explanation is that it is an intrinsic epidemic growth law, dictated by a spatially distributed community structure, where the growth in individual highly mixed communities is exponential but the longer term, local geographical spread (in the absence of global mixing) results in a power-law. This is supported by computer simulations of a metapopulation model that gives rise to predictions about the growth dynamics that are consistent with correlations found in the epidemiological data. Therefore, seeing a deviation from straight exponential growth may not be a consequence of working non-pharmaceutical interventions (except for, perhaps, restricting the air travel). Instead, this is a normal course of raging infection spread. On the practical side, this cautions us against overly optimistic interpretations of the countries epidemic development and emphasizes the need to continue improving the compliance with social distancing behavior recommendations.
Chapter 6 – Density of solid—Inorganic compounds

Publisher Summary This chapter presents the density of solid for inorganic compounds in tabular form. The tabulation is arranged by alphabetical order such as Ag, Al, Ar, and Zr to provide ease of use in quickly locating the data by using the chemical formula. The compound name and chemical abstracts registry number (CAS No) are also provided in columns. Values for representative temperature and density at the representative temperature are given in the adjacent columns. The next column provides the code for the tabulation. In preparing the tabulation, a literature search is conducted to identify data source publications. Both experimental values for the property under consideration and parameter values for estimation of the property are included in the source publications. The publications are screened, and copies of appropriate data are made. These data are keyed into the computer to provide a database of values for compounds for which experimental data are available. The database also serves as a basis to check the accuracy of the estimation methods. Upon completion of data collection, estimation of values for the remaining compounds is performed. The compilations of CRC, Daubert and Danner, Landolt and Bornstein, and Yaws are used extensively for solid density. Many of the estimates are based on extending the liquid density to the triple point.
Can Alcohol Use Disorder Recovery Include Some Heavy Drinking? A Replication and Extension up to 9 Years Following Treatment

Background Recent research indicates some individuals who engage in heavy drinking following treatment for alcohol use disorder fare as well as those who abstain with respect to psychosocial functioning, employment, life satisfaction, and mental health. The current study evaluated whether these findings replicated in an independent sample and examined associations between recovery profiles and functioning up to 6 years later. Methods Data were from the 3-year and 7- to 9-year follow-ups of subsamples initially recruited for the COMBINE study (3-year follow-up: n = 694; 30.1% female, 21.0% non-White; 7- to 9-year follow-up: n = 127; 38.9% female, 27.8% non-White). Recovery at 3 years was defined by latent profile analyses including measures of health functioning, quality of life, employment, alcohol consumption, and cannabis and other drug use. Functioning at the 7- to 9-year follow-up was assessed using single items of self-rated general health, hospitalizations, and alcohol consumption. Results We identified 4 profiles at the 3-year follow-up: (i) low-functioning frequent heavy drinkers (13.9%), (ii) low-functioning infrequent heavy drinkers (15.8%), (iii) high-functioning heavy drinkers (19.4%), and (iv) high-functioning infrequent drinkers (50.9%). At the 7- to 9-year follow-up, the 2 high-functioning profiles had the best self-rated health, and the high-functioning heavy drinking profile had significantly fewer hospitalizations than the low-functioning frequent heavy drinking profile. Conclusions Previous findings showing heterogeneity in recovery outcomes were replicated. Most treatment recipients functioned well for years after treatment, and a subset who achieved stable recovery engaged in heavy drinking and reported good health outcomes up to 9 years after treatment. Results question the long-standing emphasis on drinking practices as a primary outcome, as well as abstinence as a recovery criterion in epidemiologic and treatment outcome research and among stakeholder groups and funding/regulatory agencies. Findings support an expanded recovery research agenda that considers drinking patterns, health, life satisfaction, and functioning.
Breast Tumor Microenvironment in Black Women: A Distinct Signature of CD8+ T-Cell Exhaustion.

Background Blacks tend to have a stronger inflammatory immune response than Whites. We hypothesized that racial differences in host immunity also manifest in the tumor microenvironment, constituting part of a distinct aggressive tumor biology underlying higher mortality in Black women. Methods Pathological and gene expression profiling approaches were used for characterizing infiltrating immune cells in breast tumor microenvironment from 1315 patients from the Women's Circle of Health Study. Racial differences in tumor immune phenotypes were compared, with results validated in a publicly accessible dataset. Prognostic associations of immune phenotypes were assessed in 3 independent cohorts. Results We found marked and consistent differences in tumor immune responses between Black and White patients. Not only did tumors from Blacks display a stronger overall immune presence but also the composition and quality of immune infiltrates differed, regardless of tumor subtypes. Black patients had a stronger CD4+ and B-cell response, and further, a more exhausted CD8+ T-cell profile. A signature indicating a higher ratio of exhausted CD8+ T cells to total CD8+ T cells (ExCD8-r) was consistently associated with poorer survival, particularly among hormone receptor-positive patients. Among hormone receptor-negative patients, combinations of the absolute fraction of CD8+ T cells and ExCD8-r signature identified the CD8lowExCD8-rhigh subgroup, the most prevalent among Blacks, with the worst survival. Conclusions Our findings of a distinct exhausted CD8+ T-cell signature in Black breast cancer patients indicate an immunobiological basis for their more aggressive disease and a rationale for the use of immune checkpoint inhibitors targeting the exhaustion phenotype.
Abstract PS4-19: Evaluation of tumor-specific MHC-II expression as a biomarker

Recently MHC-II protein expression levels in breast cancer tumor cells were shown to predict response to the PD-1 inhibitor pembrolizumab on a neoadjuvant clinical trial for ER+ and TNBC (ISPY-2). To better understand this biomarker and avoid post-market issues, we aimed to investigate possible pitfalls of MHC-II/HLA-DR quantification, prevalence of HLA-DR expression in breast cancer (BC) cells and its association with clinical data in a cohort of 372 BC patents. We assessed tumor and non-tumor HLA-DR expression by multiplex fluorescence immunohistochemistry on 8 TMAs containing 372 surgical BC samples, comprised of 239 ER+ and 123 TNBCs. Patient characteristics are shown in table 1. PanCK was used to define the tumor area and HLA-DR quantification was performed by training an object classifier on QuPath. Upon visual examination, 23 samples showed patchy panCK expression. We excluded normal breast epithelium and in situ components, which showed varying degrees of HLA-DR. 44.4% of breast cancers expressed HLA-DR, with 8.3% showing high tumor expression (HLA-DRHI; ≥20% of tumor cells). TNBC showed higher prevalence of HLA-DRHI cases (35% HLADR+, 14.6% HLA-DRHI, mean tumor HLA-DR expression (% of tumor cells) 10.3%, range 0-84%) than ER+ BC (51% HLADR+, 5.4% HLA-DRHI, mean 7.4%, range 0-66.5%). In some cases, HLA-DR and panCK expression were mutually exclusive. In other cases the lack of panCK expression highlighted the presence of stromal cells within the tumor area that were not evident on HE however, only stage was an independent predictor in multivariant analyses. Tumor MHC-II expression in BC has been reported to range from 22% to 48.5% in TNBC or unselected BC, and high tumoral MHC-II expression was reported to be 6.9% in unselected BC and 36.3% in TNBC. Specific rates of HLA-DR expression in ER+ breast cancer have not been extensively investigated. Here we report a similar overall prevalence, but lower number of tumors presenting high HLA-DR expression and an association with poorer survival in ER+ BC. HLA-DR IHC is a robust assay that can be easily used to identify MCH-II high expressing tumors and scoring percentage of tumoral cells should be more reproducible than PD-L1 scoring on immune cells when assessed by a trained pathologist. Citation Format: Paula Ines Gonzalez Ericsson, Justin M Balko, Violeta Sanchez, Melinda Sanders. Evaluation of tumor-specific MHC-II expression as a biomarker [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-19.
Accurate Diagnosis of the Mycobacterium paratuberculosis Status of Cattle Herds

Programs to classify cattle herds by M. paratuberculosis infection status must satisfy buyer's concerns that cattle from tested herds are unlikely to be infected (high negative predictive value), and seller's concerns that their herds will not be erroneously, classified as infected (high positive predictive value). Veterinarians recommending these programs need confidence that a high percentage of herds will be classified correctly. Probablistic models were used to evaluate 3 diagnostic strategies that use tests of individuals to classify cattle herds by M. paratuberculosis infection status: 1) enzyme-linked immunosorbent assay (ELISA) serology; 2) culture of feces; 3) ELISA serology in series with confirmatory culture of feces.