cssi/SciSciGPT-SciSciNet huggingface dataset:
Bacillithiol has a role in Fe–S cluster biogenesis in Staphylococcus aureus

Summary Staphylococcus aureus does not produce the low-molecular-weight (LMW) thiol glutathione, but it does produce the LMW thiol bacillithiol (BSH). To better understand the roles that BSH plays in staphylococcal metabolism, we constructed and examined strains lacking BSH. Phenotypic analysis found that the BSH-deficient strains cultured either aerobically or anaerobically had growth defects that were alleviated by the addition of exogenous iron (Fe) or the amino acids leucine and isoleucine. The activities of the iron–sulfur (Fe–S) cluster-dependent enzymes LeuCD and IlvD, which are required for the biosynthesis of leucine and isoleucine, were decreased in strains lacking BSH. The BSH-deficient cells also had decreased aconitase and glutamate synthase activities, suggesting a general defect in Fe–S cluster biogenesis. The phenotypes of the BSH-deficient strains were exacerbated in strains lacking the Fe–S cluster carrier Nfu and partially suppressed by multicopy expression of either sufA or nfu, suggesting functional overlap between BSH and Fe–S carrier proteins. Biochemical analysis found that SufA bound and transferred Fe–S clusters to apo-aconitase, verifying that it serves as an Fe–S cluster carrier. The results presented are consistent with the hypothesis that BSH has roles in Fe homeostasis and the carriage of Fe–S clusters to apo-proteins in S. aureus.
The History of EEG Hans Berger: Psychophysiologist. A Historical Vignette

Historically, Hans Berger deserves undisputed credit for the discovery of the human electroencephalograph. It is rarely reported that his discovery was the result of a 40-year search for the physical basis of mind. The search began as a result of a near-death "telepathic" experience in his youth. The history of Hans Berger reveals him to be a dedicated scientist fascinated with psychophysiology and, in the end, a tragic figure.
Interactions between taurine and ethanol in the central nervous system.

This purpose of this review will be to summarize the interactions between the endogenous amino acid taurine and ethyl alcohol (ethanol) in the central nervous system (CNS). Taurine is one of the most abundant amino acids in the CNS and plays an integral role in physiological processes such as osmoregulation, neuroprotection and neuromodulation. Both taurine and ethanol exert positive allosteric modulatory effects on neuronal ligand-gated chloride channels (i.e., GABAA and glycine receptors) as well as inhibitory effects on other ligand- and voltage-gated cation channels (i.e., NMDA and Ca2+ channels). Behavioral evidence suggests that taurine can alter the locomotor stimulatory, sedating, and motivational effects of ethanol in a strongly dose-dependent manner. Microdialysis studies have revealed that ethanol elevates extracellular levels of taurine in numerous brain regions, although the functional consequences of this phenomenon are currently unknown. Finally, taurine and several related molecules including the homotaurine derivative acamprosate (calcium acetylhomotaurinate) can reduce ethanol self-administration and relapse to drinking in both animals and humans. Taken together, these data suggest that the endogenous taurine system may be an important modulator of effects of ethanol on the nervous system, and may represent a novel therapeutic avenue for the development of medications to treat alcohol abuse and alcoholism.
Histopathology of broken‐back syndrome in channel catfish

Channel catfish, Ictdurus punctatus, were fed a vitamin C-free diet under laboratory conditions. Specimens with ‘broken-back’ syndrome had vertebral injury due to osteoporosis, abnormally increased ossification, and dysplasia. There was also impairment of systemic collagen fibres and atrophy of the pancreas and haemopoietic tissue.
Sticks, plates, and blobs: a three-dimensional object representation for scene analysis

In this paper, we describe a relational modeling technique which categorizes three-dimensional objects at a gross level. These models may then be used to classify and recognize two dimensional views of the object, in a scene analysis system.
Automatic dysphonia recognition using biologically-inspired amplitude-modulation features

A dysphonia, or disorder of the mechanisms of phonation in the larynx, can create time-varying amplitude fluctuations in the voice. A model for band-dependent analysis of this amplitude modulation (AM) phenomenon in dysphonic speech is developed from a traditional communications engineering perspective. This perspective challenges current dysphonia analysis methods that analyze AM in the time-domain signal. An automatic dysphonia recognition system is designed to exploit AM in voice using a biologically inspired model of the inferior colliculus. This system, built upon a Gaussian-mixture-model (GMM) classification backend, recognizes the presence of dysphonia in the voice signal. Recognition experiments using data obtained from the Kay elemetrics voice disorders database suggest that the system provides complementary information to state-of-the-art mel-cepstral features. We present dysphonia recognition as an approach to developing features that capture glottal source differences in normal speech.
Antidepressant medication use, depression, and the risk of preeclampsia

Objective To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. Methods We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. Results The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for selective serotonin reuptake inhibitor (SSRI) use, although a nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Conclusion Study findings suggest that antidepressant use during pregnancy may increase the risk of preeclampsia, especially use during the second trimester.
Imposing WTO Disciplines on Domestic Support: An Assessment of the Doha Round Approach

SUMMARY: The elements of the approach to disciplining domestic support for agriculture in the Doha round of WTO negotiations are evaluated using data for a selection of OECD countries. Despite a substantial increase in complexity in comparison to the Uruguay Round Agreement, the new approach is unlikely to require real reductions in trade-distorting support. As a result it is unlikely to stimulate further reforms in domestic agricultural policies in OECD countries.
Victory without power: The Pm-Pendulum forecast

The “PM and Pendulum” model was adjusted for the 2015 General Election to take account of the Liberal-Democratic participation in government and the SNP surge. So adjusted, the model predicts a Tory vote victory by 3.4 percent over Labour. The seat forecast puts the Tories ahead with 287 seats to 263 for Labour, with 41 for the SNP. Thus another Hung Parliament! Ex-post estimates show that without the Lib-Dem adjustments the model would have predicted a Conservative majority.
Musical Witness and Holocaust Representation

Introduction 1. The composer as witness: Arnold Schoenberg's A Survivor from Warsaw 2. The philosopher as witness: Theodor Adorno's A Survivor from Warsaw 3. The composer as witness: Hanns Eisler's Nuit et Brouillard 4. The state as witness: Judische Chronik in the German Democratic Republic 5. The composer as witness: Steve Reich's Different Trains Epilogue.
Single-Molecule Fluorescence Imaging of Interfacial DNA Hybridization Kinetics at Selective Capture Surfaces

Accurate knowledge of the kinetics of complementary oligonucleotide hybridization is integral to the design and understanding of DNA-based biosensors. In this work, single-molecule fluorescence imaging is applied to measuring rates of hybridization between fluorescently labeled target ssDNA and unlabeled probe ssDNA immobilized on glass surfaces. In the absence of probe site labeling, the capture surface must be highly selective to avoid the influence of nonspecific adsorption on the interpretation of single-molecule imaging results. This is accomplished by increasing the probe molecule site densities by a factor of ∼100 compared to optically resolvable sites so that nonspecific interactions compete with a much greater number of capture sites and by immobilizing sulfonate groups to passivate the surface between probe strands. The resulting substrates exhibit very low nonspecific adsorption, and the selectivity for binding a complementary target sequence exceeds that of a scrambled sequence by nearly 3 ord...
On Accuracy of Classification-Based Keystroke Dynamics for Continuous User Authentication

The aim of this research is to advance the user active authentication using keystroke dynamics. Through this research, we assess the performance and influence of various keystroke features on keystroke dynamics authentication systems. In particular, we investigate the performance of keystroke features on a subset of most frequently used English words. The performance of four features such as i) key duration, ii) flight time latency, iii) diagraph time latency, and iv) word total time duration are analyzed. Two machine learning techniques are employed for assessing keystroke authentications. The selected classification methods are support vector machine (SVM), and k-nearest neighbor classifier (K-NN). The logged experimental data are captured for 28 users. The experimental results show that key duration time offers the best performance result among all four keystroke features, followed by word total time.
Evaluating the South Oaks Gambling Screen With DSM-IV and DSM-5 Criteria: Results From a Diverse Community Sample of Gamblers

Despite widespread use, the South Oaks Gambling Screen (SOGS) has been criticized for excessive false positives as an indicator of pathological gambling (PG), and for items that misalign with PG criteria. We examine the relationship between SOGS scores and PG symptoms and convergent validity with regard to personality, mood, and addictive behaviors in a sample of 353 gamblers. SOGS scores correlated r = .66 with both DSM-IV and DSM-5 symptoms, and they manifested similar correlations with external criteria (intraclass correlation of .95). However, 195 false positives and 1 false negative were observed when using the recommended cut point, yielding an 81% false alarm rate. For uses with DSM-IV criteria, a cut point of 10 would retain high sensitivity with greater specificity and fewer false positives. For DSM-5 criteria, we advocate a cut point of 8 for use as a clinical screen and a cut point of 12 for prevalence and pseudo-experimental studies.
An Interview with Deborah Lasher, RN, MPH, CCRC, CCRA

W e are pleased to share the career path of one of ACRP’s most prominent volunteers, Deborah Lasher, RN, MPH, CCRC, CCRA. Deborah was most recently chair of the Global Conference Planning Committee for the 2014 Global Conference in San Antonio, Texas. In this column, she shares more about how she
Male Multiple Ejaculatory Orgasms: A Case Study

There is a paucity of research concerning male multiple orgasms, with or without ejaculation. The purpose of this study was to document, in the laboratory setting, the reported occurrence of male m...
Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems

Recently, semirational approaches that rely on combinatorial assembly of characterized DNA components have been used to engineer biosynthetic pathways. In practice, however, it is not practical to assemble and test millions of pathway variants in order to elucidate how different DNA components affect the behavior of a pathway. To address this challenge, we apply a rigorous mathematical approach known as design of experiments (DOE) that can be used to construct empirical models of system behavior without testing all variants. To support this approach, we have developed a tool named Double Dutch, which uses a formal grammar and heuristic algorithms to automate the process of DOE library design. Compared to designing by hand, Double Dutch enables users to more efficiently and scalably design libraries of pathway variants that can be used in a DOE framework and uniquely provides a means to flexibly balance design considerations of statistical analysis, construction cost, and risk of homologous recombination, ...
A fiber optic probe to measure spatially resolved diffuse reflectance in the sub-diffusion regime for in-vivo use(Conference Presentation)

We present an ultra-simple miniature fiber optic probe to measure spatially and spectrally resolved diffuse reflectance in the sub-diffuse regime (i.e. measurements with source-detector separation less than a transport mean free path) in-vivo. This probe has a robust and simple design with a small footprint (<.5 mm diameter). We show that our probe has sensitivity to structures scattering light an order of magnitude smaller than the diffraction limit, and thus can be used to quantify alterations in the very smallest structures in tissue (e.g. organelles, chromatin, collagen fibers, etc.). Specifically, the probe samples the spatial profile of diffuse reflectance in the sub-diffusion regime (P(r), r<<1 mm). P(r) can be used to quantify the entire shape of the phase function, F(θ). The shape of the refractive index correlation function Bn(rd) (through which the spatial distribution of mass is defined) can be analytically derived from the shape of F(θ) through application of the Born approximation. Therefor measurements of P(r) can elucidate F(θ) and Bn(rd). This ability has tremendous potential for use as a diagnostic tool and broad applications for probing the nanoscale environment of tissue in-vivo.
Effects of porcine somatotropin administration on porcine muscles located within different regions of the body.

This research was conducted to evaluate the characteristics of muscle fiber growth and the effects of porcine somatotropin (pST; 100 micrograms.kg-1 BW.d-1) administration on the morphology of 12 muscles located in different regions of the body in barrows growing from 20 to 90 kg BW. In the course of the growth of control pigs, the percentage distribution of beta R fibers did not show any changes in all 12 muscles, whereas the percentage of alpha R and alpha W fibers changed in different patterns in different muscles. The administration of pST had no effect on fiber type distribution. The cross-sectional area of alpha W fibers was the largest of the three fiber types, and beta R and alpha R fibers were of similar size in all muscles. All fiber types in all muscles increased in cross-sectional area by an average of 120% from 20 to 60 kg BW. After 60 kg BW, the growth of alpha W fibers in seven (early maturing) muscles and alpha R fibers in one muscle out of the 12 muscles was not apparent. The increase of their cross-sectional area was an average of 12%, but the area of the other muscle fibers continued to increase by an average of 38% until 90 kg BW. The administration of pST increased the area of alpha W fibers in four out of seven of these early-maturing muscles by an average of 25%, suggesting some possible relationships between pST effects and the rate of muscle fiber maturation. Most of the muscles that responded to pST treatment were located in hindlimb region.
Abstract B52: Targeted LC-MS/MS metabolic profiling for colon cancer progression monitoring

Introduction: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and a major cause of human morbidity and mortality. A number of current efforts are focused on earlier detection of colon cancer using a variety of technologies including genomics, proteomics and metabolomics. Research focused on CRC disease status surveillance using metabolomics or other approaches has not been reported; Close monitoring of disease progression (DP) in CRC can be critical for patients9 prognosis management and treatment decisions. In this study we investigate a targeted LC-MS/MS approach for serum metabolic profiling to monitor and predict patient disease progression, using a panel of significantly altered metabolites as potential biomarkers. Methods: 59 serum samples from 21 CRC patients were analyzed, including 23 samples from DP patients and 36 from other CRC disease status (e.g., stable disease and complete remission). Chromatographic separations were performed via an Agilent HPLC system installed with two hydrophilic interaction chromatography (HILIC) columns, and then targeted data acquisition was performed in multiple-reaction-monitoring (MRM) mode using an AB Sciex QTrap 5500 mass spectrometer. We monitored 106 and 58 MRM transitions in negative and positive mode, respectively. Univariate and multivariate statistical analyses (such as the Mann- Whitney U-test and PLS-DA) were applied for metabolite biomarker discovery and model development on a selected set of promising biomarker candidates. Monte Carlo cross validation (MCCV) was performed to evaluate model robustness. Results and conclusion: LC-MS/MS targeted analysis provided a robust system for metabolic profiling of CRC patient disease status monitoring using serum samples. Targeted screening of 164 metabolites, representing more than 20 different classes (such as amino acids, carboxylic acids, pyridines, and etc.) and from 25 important metabolic pathways (e.g., TCA cycle, amino acid metabolism, purine and pyrimidine metabolism, and glycolysis, and etc.) was performed using both positive and negative ionization modes. 131 metabolites could be reproducibly detected in the serum samples, with an average CV of 7.1% measured in pooled serum quality control samples. After univariate analysis, 36 metabolites from different classes, such as monosaccharides, amino acids, carboxylic acids and nucleosides, showed a significant statistical difference (p Citation Format: Jiangjiang Zhu, Danijel Djukovic, Lingli Deng, Lingli Deng, Haiwei Gu, Farhan Himmati, Mohammad Abu Zaid, E. Gabriela Chiorean, E. Gabriela Chiorean, Daniel Raftery, Daniel Raftery. Targeted LC-MS/MS metabolic profiling for colon cancer progression monitoring. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B52.
The Hematopoietic Microenvironment: Stromal Extracellular Matrix Components As Growth Regulators For Human Hematopoietic Progenitors.

(1999). Stromal Extracellular Matrix Components As Growth Regulators For Human Hematopoietic Progenitors. Hematology: Vol. 4, No. 4, pp. 321-333.
Preparative chromatography and analysis of molecular weight fractions of gelatin

AbstractPreparative scale gel filtration chromatography has been used to isolate different molecular weight fractions of gelatin for subsequent chemical analysis. The broad molecular weight distribution of gelatin was fractionated into four regions corresponding to high molecular weight, beta, alpha and low molecular weight material. Characterization of the isolated fractions included molecular weight distribution, amino acid composition, total active sulphur measured by cysleic acid analysis after oxidative hydrolysis and analysis of the pyridinoline crosslinks. A limed bovine ossein gelatin was characterized by these ttxhniques.
Composing the Will to Power: John Dewey on Democratic Rhetorical Education

In order to highlight the genuinely radical nature of John Dewey’s educational and democratic vision this essay articulates a vision of contemporary rhetorical education that is grounded in a pragmatic rereading of Friedrich Nietzsche’s concept of the “will to power.” Drawing from Dewey’s treatment of the will to power in Human Nature and Conduct, I argue that rhetorical pedagogy seeks to arouse, channel, and finally compose the impulses of students through the activity of intelligence in such a way that reflects and advocates for students’ interests within a democratic ethic of advocacy, criticism, and deliberation.
Abstract 3172: CCL9 induction in myeloid cells of the premetastatic niche enhances tumor cell survival and metastatic colonization

Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here we report that chemokine CCL9 was highly induced in Gr-1+CD11b+ immature myeloid cells and in premetastatic lung of mice bearing 4T1 mammary tumor and B16 melanoma. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our studies identify CCL9 as a key pro-survival factor for cancer cells in the premetastatic organ. Interestingly, the expression of CCL9 in myeloid cells is regulated by TGF-β signaling as overexpression of CCL9 in myeloid cells lacking TGF-β signaling rescued the tumor metastasis defect observed in mice with myeloid-specific deletion of TGF-β signaling. These data together with our previous report of a fundamental role of myeloid TGF-β signaling in host compromised immune surveillance (Cancer Discovery 2013); demonstrate that myeloid-specific TGF-β signaling constitutes an essential component of the metastasis-promoting puzzle of TGF-β. This finding is different from TGF-β signaling in fibroblasts and a variety of epithelial cells, as well as T cells in which the TGF-β signaling functions as a tumor suppressor. This new understanding of TGF-β at the interface of tumor and host may provide insight into how TGF-β switches from a tumor suppressor to a tumor promoter, a long-standing challenge in cancer biology field. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. Additionally, targeting CCL9 may avoid the adverse effects of TGF-β-targeted therapy. Citation Format: Hannah HY Yan, Yanli Pang, Kent Hunter, Chand Khanna, Li Yang. CCL9 induction in myeloid cells of the premetastatic niche enhances tumor cell survival and metastatic colonization. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3172. doi:10.1158/1538-7445.AM2015-3172
Chromatin dynamics regulate mesenchymal stem cell lineage specification and differentiation to osteogenesis

Multipotent mesenchymal stromal cells (MSCs) are critical for regeneration of multiple tissues. Epigenetic mechanisms are fundamental regulators of lineage specification and cell fate, and as such, we addressed the question of which epigenetic modifications characterize the transition of nascent MSCs to a tissue specific MSC-derived phenotype. By profiling the temporal changes of seven histone marks correlated to gene expression during proliferation, early commitment, matrix deposition, and mineralization stages, we identified distinct epigenetic mechanisms that regulate transcriptional programs necessary for tissue-specific phenotype development. Patterns of stage-specific enrichment of histone modifications revealed distinct modes of repression and activation of gene expression that would not be detected using single endpoint analysis. We discovered that at commitment, H3K27me3 is removed from genes that are upregulated and is not acquired on downregulated genes. Additionally, we found that the absence of H3K4me3 modification at promoters defined a subset of osteoblast-specific upregulated genes, indicating that acquisition of acetyl modifications drive activation of these genes. Significantly, loss or gain of H3K36me3 was the primary predictor of dynamic changes in temporal gene expression. Using unsupervised pattern discovery analysis the signature of osteogenic-related histone modifications identified novel functional cis regulatory modules associated with enhancer regions that control tissue-specific genes. Our work provides a cornerstone to understand the epigenetic regulation of transcriptional programs that are important for MSC lineage commitment and lineage, as well as insights to facilitate MSC-based therapeutic interventions.
Illegal gambling businesses & organized crime: an analysis of federal convictions

Illegal gambling operations have been alleged to support organized crime and victimize participants, rather than benefit them. This is said to occur through cheating in the games provided, defrauding the government of tax revenue, and funding other illicit and criminal activities. What has been missing is a systematic analysis of actual cases involving illegal gambling businesses to determine precisely who is involved, how these businesses operate, the nature of the threat posed, and the law enforcement response to it. The analysis reported here examines all federal convictions involving operation of illegal gambling businesses during a single year. There were more than 80 persons charged and convicted of participation in illegal gambling businesses, centered around 40 distinct enterprises. The results indicate that illegal gambling businesses in the United States are long-term operations consisting of four general types, and that enforcement of existing laws, particularly related to illegal online sports betting, are not working effectively.
Haptic fMRI: Reliability and performance of electromagnetic haptic interfaces for motion and force neuroimaging experiments

Haptic interfaces compatible with functional magnetic resonance imaging (Haptic fMRI) promise to enable rich motor neuroscience experiments that study how humans perform complex manipulation tasks. Here, we present a large-scale study (176 scans runs, 33 scan sessions) that characterizes the reliability and performance of one such electromagnetically actuated device, Haptic fMRI Interface 3 (HFI-3). We outline engineering advances that ensured HFI-3 did not interfere with fMRI measurements. Observed fMRI temporal noise levels with HFI-3 operating were at the fMRI baseline (0.8% noise to signal). We also present results from HFI-3 experiments demonstrating that high resolution fMRI can be used to study spatio-temporal patterns of fMRI blood oxygenation dependent (BOLD) activation. These experiments include motor planning, goal-directed reaching, and visually-guided force control. Observed fMRI responses are consistent with existing literature, which supports Haptic fMRI's effectiveness at studying the brain's motor regions.
Brain Response to Extracranial Pressure Excitation Imaged in vivo by MR Elastography

Traumatic brain injuries (TBI) are common, and often lead to permanent cognitive impairment. Despite the prevalence and severity of TBI, the condition remains poorly understood. Computer simulations of injury mechanics offer enormous potential for the study of TBI; however, computer models require accurate descriptions of tissue constitutive behavior and brain-skull boundary conditions. Magnetic resonance elastography (MRE) is a non-invasive imaging modality that provides quantitative spatial maps of tissue stiffness in vivo. MRE is performed by inducing micron-amplitude propagating shear waves into tissue and imaging the resulting motion with a specialized “motion-sensitive” MRI pulse sequence. Invoking a restricted form of Navier’s equation these data can be inverted to estimate material stiffness. As such, clinical interest in MRE has largely been driven by the direct empirical relationship between tissue stiffness and health. However, the so-called “raw” MRE data themselves (3-D displacement measurements) and calculated strains can elucidate loading paths, anatomic boundaries and the dynamic response of the intact human head. In this study, we use the MRE imaging technique to measure in vivo displacement fields of brain motion as the cranium is exposed to acoustic frequency pressure excitation (45, 60, 80 Hz) and calculate the resulting shear-strain fields (2-D).
Paraesophageal Hernias: Indications and Surgical Treatment

Laparoscopic paraesophageal hiatal hernia repair is a complex operation that requires experience with advanced minimally invasive surgical techniques, as well as an expertise in both the anatomy and physiology of the esophagus and stomach. When performed correctly the operation should result in a high rate of symptomatic resolution with a low complication profile, despite often being performed in patients who are elderly with multiple medical comorbidities. However, if the principles of a proper repair are not followed, patients can be left with persistent dysphagia and/or gastroesophageal reflux, resulting in a worse quality of life than they had preoperatively and possibly necessitating reoperation. This chapter outlines the preoperative assessment, evaluation, and indications for surgery in patients presenting with paraesophageal hernia. The key steps and components of a laparoscopic repair are detailed, with an emphasis on adherence to the fundamentals of creating a functional repair. These include creating a setup and port placement that allows for efficient and effective operating, complete dissection and reduction of the hernia sac, mobilization of the distal esophagus, performing a tension-free crural repair, and creation of an effective antireflux fundoplication. The decisions of when to perform an esophageal lengthening procedure and/or reinforce the crural repair with a mesh are also addressed. While surgeons must tailor their technique to their own operating style and individual patient anatomy, if these basic principles and steps are adhered to, the operation should lead to successful and durable outcomes on a consistent basis.
Appraisal after Dell

This Essay examines the state of appraisal in Delaware after the Delaware Supreme Court’s decisions in DFC Global (July 2017) and Dell (December 2017). In these two cases, the Supreme Court reversed Chancery Court rulings that “fair value” exceeded the deal price. In doing so the Supreme Court strongly signaled that deal price should receive presumptive weight as long as the deal process is good. The question then becomes how good the deal process must be in order to gain deference to the deal price. In Dell, the Chancery Court found that the deal process was good enough to satisfy fiduciary duties but not good enough to warrant deference to the deal price. The Supreme Court revisited (and in some instances, mischaracterized) key facts from the record to conclude that the Chancery Court’s ruling constituted an “abuse of discretion.” This Essay concludes with implications for practitioners and courts. An earlier version of this Essay is titled Using the Deal Price for Determining "Fair Value" in Appraisal Proceedings.
6.27 – Neurotoxicology of Metals

A large number of elements in nature can be classified as metals. Many of these, such as copper, iron, and zinc, are important to life, while others, for example, mercury, lead, and cadmium, have adverse effects on the biological system and may be referred to as toxic metals. The most significant neurotoxic metals are mercury, lead, arsenic, cadmium, aluminum, and manganese. Some metals exist as organometals, such as methylmercury, alkyl leads, triethyltin, and trimethyltin, which are also potent neurotoxicants. A notable problem in studying the neurotoxicity of metals is that some metals that are essential elements for normal cellular function are toxic at high concentrations or when encountered in their free forms unbound to typical cellular substrates. Understanding mechanisms by which endogenous and xenobiotic metals perturb normal cellular function is central to identifying and predicting neurotoxic outcomes of exposure. The intent of this chapter is therefore to provide a basic understanding of the source, routes of exposure, and mechanism of action for the major classes of metals with known neurotoxic liability, rather than to provide an exhaustive compendium of all reported neurotoxic effects. There are many excellent published reviews for the metals discussed, and the reader is encouraged to consult these and the references cited for more detailed information.
Advertising and promotional effects on consumer service firm sales: Media ad spend and quality matter for driving restaurant sales

ABSTRACT This study focuses on the effects of different marketing-communications tools on company performance, namely how advertising-execution quality, media spending, and sales promotions differentially influence changes in sales revenue. The analysis employs five years of aggregated monthly data on nine leading brands in a consumer-services sector, quick-serve restaurants, an often-overlooked area with high marketing-communications expenditures. The findings illustrate that advertising spending and then execution quality mattered most for changes in sales revenue. Internet advertising had no effect for most companies, and sales promotions either were not significant or were related negatively to changes in sales.
Ligand Binding and Signaling of HARE/Stabilin-2

The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external environment of the cell. Stabilin-1 was the first receptor to be cloned, though the biological activity of Hyaluronic Acid Receptor for Endocytosis (HARE)/Stabilin-2 was observed about 10 years prior to the cloning of Stabilin-1. Stabilin-1 has a more diverse expression profile among the tissues than HARE/Stabilin-2. This review will focus on HARE/Stabilin-2 and its interactions with hyaluronan, heparin, and phosphorothioate antisense oligonucleotides and what is known about how this receptor participates in signaling upon ligand binding.
How I investigate bone marrow necrosis

Hematopathologists encounter bone marrow biopsy specimens with marrow necrosis relatively infrequently; when necrosis is seen, determining the clinical significance can be challenging. While bone marrow necrosis is not uncommon in site-directed biopsy specimens or autopsy material, substantial necrosis is much less common in nondirected bone marrow biopsy specimens. Retrospective review showed the prevalence of bone marrow necrosis to vary between 0.3% and 2% antemortem, depending on the patient population. Numerous causes of bone marrow necrosis have been identified, including malignancy, radiation/chemotherapy, medication, infection, autoimmune disease, disseminated intravascular coagulation, antiphospholipid syndrome and other thrombotic disorders, granulocyte-colony stimulating factor (G-CSF) exposure, and hemoglobinopathies. Clinical findings associated with bone marrow necrosis include bone pain and fever, cytopenias, elevated LDH and ferritin, and leukoerythroblastosis. Rarely, such as in fat embolization syndrome (FES), bone marrow necrosis can be associated with thrombotic microangiopathy, neurologic dysfunction, and multiorgan failure. A thorough review of the patient's clinical record (including medical history, clinical presentation, and other laboratory findings), a thorough morphologic review of the bone marrow with appropriate ancillary stains, and an appreciation of the causes of bone marrow necrosis in different patient populations are required to determine the underlying cause of bone marrow necrosis. The purpose of this review is to present a strategy for evaluation of bone marrow necrosis found in an antemortem biopsy specimen.
Experience with a "Feed and Swaddle" program in infants up to six months of age.

BACKGROUND Feed and swaddle is a technique in which an infant is fed and allowed to fall asleep to facilitate diagnostic imaging. This study reviews our experience and diagnostic success in premature and term infants up to 6 months old undergoing brain magnetic resonance imaging (MRI) using a feed and swaddle technique and with comparable patients imaged under anesthesia. METHODS We reviewed the charts of all infants ≤6 months who underwent brain MRI at our institution between 1 January 2013 and 31 March 2016. We recorded and analyzed demographic information, scan indication, scan length, prematurity status, anesthetic technique if used, complications, and diagnostic success or failure. RESULTS One hundred and sixty-four term infants underwent brain MRI using a feed and swaddle technique. The success rate in term infants <90 days was 91.1% (113/124) versus 95.0% (38/40) in infants ≥90 days and ≤181 days old. Fifty-three premature infants underwent feed and swaddle for brain MRI with a diagnostic success rate of 92.5% (49/53). No complications were noted in any feed and swaddle patients. Those who received anesthesia had a diagnostic success rate of 100% (70/70) but experienced complications including hypoxemia, 14.3% (10/70); hypothermia, 18.9% (10/53); bradycardia, 10.1% (7/69); and hypotension, 4.2% (3/70). CONCLUSION Given the high rate of success and absence of complications with feed and swaddle in children ≤6 months for brain MRI and the presence of anesthesia-related complications, most infants should undergo a trial of feed and swaddle prior to undergoing brain MRI with anesthesia.
Mucinous lesions of the breast: potpourri of old and new

Abstract Mucinous lesions of the breast encompass a range of benign and malignant entities characterized by extracellular mucin production. Increased sampling of mammary calcifications has identified a range of mucocele-like lesions, which are associated with benign proliferative and atypical intraductal epithelial proliferation ranging in architectural complexity from flat epithelial atypia to ductal carcinoma in situ. Mucinous carcinoma is a unique histologic subtype of breast cancer with a good prognosis. Mucinous carcinoma, especially in males and older females, can arise in association with solid papillary carcinoma. Recent molecular studies reveal distinct genomic changes in mucinous carcinoma. Micropapillary mucinous carcinoma is a recently described histologic variant of breast cancer with aggressive clinical features and poorer outcome. Not all mucinous lesions are of ductal epithelial phenotype; rarely, lobular carcinoma can present with extracellular mucin. This concise review discusses clinical features, histological findings, and differential diagnoses of mucinous lesions of the breast, including common and some rare lesions as well as recently described entities.
Risk Profile, Efficacy and Safety of Rituximab in Patients with Relapsed or Refractory Idiopathic Thrombocytopenic Purpura in a Minority Cohort with Long Term Follow up

Background: Idiopathic Thrombocytopenic Purpura (ITP) is a common hematological disorder. We sort to characterize the risk profiles and efficacy of rituximab in relapsed or refractory ITP in a largely minority cohort. Methods: 23 patients (pts) with relapsed or refractory ITP treated with Rituximab were identified and studied as a retrospective cohort. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student’s T test, categorical data via Fisher’s exact test and time to progression data was analyzed via Kaplan Meier life table analysis and log rank test. Results: Of the 23 patients, 20 female (87%), 3 male (13%). median age at diagnosis was 45 yr (range 20–66).9 pt were African American (39%), 9 Hispanics (39%), 4 Asian (17.4%), 1 Caucasian(4.3%), 9 (39.6%) had more than one co morbidities, 17 (73.8%) had received 3 or more treatment regimens. All pt received steroids, 18 (78.3%) received IVIg, 13 (56.6%) Anti D immunoglobulin, 5 (21.7%) Vincristine, 3 (13%) Azathioprine, 2(8.7%) Cyclophosamide, 6 (26.1%) underwent a Splenectomy before Rituximab therapy. The median time from diagnosis to rituximab therapy was 15 months (range 1 to 269). Median platelet count before rituximab therapy was 11 (range 3 to 200). Rituximab was administered at the dose of 375mg/m2 IV once a week for 4 weeks. The response rate was 47.8%. Response was defined as Complete response, platelet count of > 100 × 109/L, Partial response >50 × 109/L. 9 pt (39%) achieved complete response, 2 pt (8.7%) achieved partial response. 12 pt (52.2%) did not respond. Median time to response was 13.5 days (range 1–30). There was no statistically significant difference in the response when compared by gender (p=0.64), race (p= 0.398), prior splenectomy (p=0.64), prior anti D immunoglobulin (p=1.0), prior Vincristine (p=1.0), prior cyclophosamide (p=.45), prior azathioprine (p=1.0). Four pt (17.4%) had a serious adverse reaction to rituximab. One pt had diffuse hives after infusion, three pt developed diffuse pancytopenia, two pts had gram negative sepsis and died. The median follow up after rituximab therapy was 18 months (range 1–60). The median time to relapse was 7 months (range of 1 to 59). There was no statistically significant difference in time to relapse among gender (p=0.19), race (p= 0.45), Prior splenectomy (p=0.86), prior Anti D immunoglobulin (p=0.32), prior vincristine (p=0.75). Conclusion: In this primarily minority based cohort the response rate to Rituximab (48% vs. 62%) and duration of response (7 months vs. 10.5 months) was lower than other published data but the rate of serious adverse events (17% vs. 7%) was higher. Rituximab must be used cautiously in this sub group of patients. There is need for a randomized controlled clinical trail to assess the efficacy of Rituximab in this population and further studies are warranted in minority populations.
Harm-Benefit Analyses Can Be Harmful

Harm-benefit analyses (HBAs) are becoming de rigueur with some governmental regulatory agencies and popular with local institutional animal care and use committees (or their equivalents), the latter due, in part, to the adoption of HBAs as an international accreditation standard. Such analyses are employed as an attempt to balance potential or actual pain or distress imposed on laboratory animals against scientists' justifications for those impositions. The outcomes of those analyses are then supposed to be included in an official assessment of whether a given animal protocol should be approved as proposed. While commendable in theory as a means to avoid or minimize animal suffering, HBAs come with a flawed premise. Establishing an accurate prediction of benefit, especially for so-called "basic" research (vs "applied" research, such as in vivo testing for product development or batch release), is often impossible given the uncertain nature of experimental outcomes and the eventual value of those results. That impossibility, in turn, risks disapproving a legitimate research proposal that might have yielded important new knowledge if it had been allowed to proceed. Separately, the anticipated harm to which the animal would be subjected should similarly be scrutinized with an aim to refine that harm regardless of purported benefits if the protocol is approved. The intentions of this essay are to reflect on the potential harm and benefit of the HBA itself, highlight how HBAs may be helpful in advancing refinements, and propose alternative approaches to both parts of the equation in the assessment process.
Exploring the Form and the Function: a Review of Science Discourse Frameworks in the Service of Research and Practice

The importance of how classroom discourse can be used to support science learning has gained national attention with respect to both science teaching and research across K12 and higher education. In this review article, we examine a commonly referenced set of nine frameworks for use in science classrooms. Specifically, we examine the ways in which various frameworks emphasize the structure (i.e., form) or practical use (i.e., function) of language across classroom settings, and the impact of such an emphasis on the facilitation and analysis of science classroom discourse. The findings from this review should help researchers investigate and educators facilitate classroom discourse in ways that ensure that all students can participate in and demonstrate their scientific understanding.
"Free food on campus!": Using instructional technology to reduce university food waste and student food insecurity.

As food insecurity among college students in the United States continues to rise, large quantities of food are wasted on college campuses. This paper presents a simple, low-cost approach to address...
Godzilla as the Bridge: The Destruction of Hiroshima, Nagasaki, and Fukushima

After the Triple Disasters of the Tohoku earthquake, tsunami, and subsequent nuclear accident at Fukushima Daiichi on March 11, 2011, visual artists around the world repurposed the image of Godzilla to represent the Japanese urban destruction, creating a visual bridge between that day and the destruction of Hiroshima and Nagasaki in August 1945.
It's in the syllabus … or is it? How biology syllabi can serve as communication tools for creating inclusive classrooms at a large-enrollment research institution

Syllabi are usually required by institutions of higher education and often are the first exposure that students have to a particular course. Instructors can use syllabi as a mechanism to convey imp...
Structures of Neisseria gonorrhoeae MtrR-operator complexes reveal molecular mechanisms of DNA recognition and antibiotic resistance-conferring clinical mutations

Mutations within the mtrR gene are commonly found amongst multidrug resistant clinical isolates of Neisseria gonorrhoeae, which has been labelled a superbug by the Centers for Disease Control and Prevention. These mutations appear to contribute to antibiotic resistance by interfering with the ability of MtrR to bind to and repress expression of its target genes, which include the mtrCDE multidrug efflux transporter genes and the rpoH oxidative stress response sigma factor gene. However, the DNA-recognition mechanism of MtrR and the consensus sequence within these operators to which MtrR binds has remained unknown. In this work, we report the crystal structures of MtrR bound to the mtrCDE and rpoH operators, which reveal a conserved, but degenerate, DNA consensus binding site 5'-MCRTRCRN4YGYAYGK-3'. We complement our structural data with a comprehensive mutational analysis of key MtrR-DNA contacts to reveal their importance for MtrR-DNA binding both in vitro and in vivo. Furthermore, we model and generate common clinical mutations of MtrR to provide plausible biochemical explanations for the contribution of these mutations to multidrug resistance in N. gonorrhoeae. Collectively, our findings unveil key biological mechanisms underlying the global stress responses of N. gonorrhoeae.
Telemental Health during a Pandemic: Third Space Conversations

This article presents Intersubjectivity and Intersectionality, theoretical frameworks used to guide telemental health during a pandemic that has underscored issues of power and privilege. Intersubj...