cssi/SciSciGPT-SciSciNet huggingface dataset:
A Comprehensive Whole Genome Bacterial Phylogeny Using Correlated Peptide Motifs Defined in a High Dimensional Vector Space

As whole genome sequences continue to expand in number and complexity, effective methods for comparing and categorizing both genes and species represented within extremely large datasets are required. Methods introduced to date have generally utilized incomplete and likely insufficient subsets of the available data. We have developed an accurate and efficient method for producing robust gene and species phylogenies using very large whole genome protein datasets. This method relies on multidimensional protein vector definitions supplied by the singular value decomposition (SVD) of a large sparse data matrix in which each protein is uniquely represented as a vector of overlapping tetrapeptide frequencies. Quantitative pairwise estimates of species similarity were obtained by summing the protein vectors to form species vectors, then determining the cosines of the angles between species vectors. Evolutionary trees produced using this method confirmed many accepted prokaryotic relationships. However, several unconventional relationships were also noted. In addition, we demonstrate that many of the SVD-derived right basis vectors represent particular conserved protein families, while many of the corresponding left basis vectors describe conserved motifs within these families as sets of correlated peptides (copeps). This analysis represents the most detailed simultaneous comparison of prokaryotic genes and species available to date.
Getting to the roots of it: Genetic and hormonal control of root architecture.

Root system architecture (RSA)--the spatial configuration of a root system--is an important developmental and agronomic trait, with implications for overall plant architecture, growth rate and yield, abiotic stress resistance, nutrient uptake, and developmental plasticity in response to environmental changes. Root architecture is modulated by intrinsic, hormone-mediated pathways, intersecting with pathways that perceive and respond to external, environmental signals. The recent development of several non-invasive 2D and 3D root imaging systems has enhanced our ability to accurately observe and quantify architectural traits on complex whole-root systems. Coupled with the powerful marker-based genotyping and sequencing platforms currently available, these root phenotyping technologies lend themselves to large-scale genome-wide association studies (GWAS), and can speed the identification and characterization of the genes and pathways involved in root system development. This capability provides the foundation for examining the contribution of root architectural traits to the performance of crop varieties in diverse environments. This review focuses on our current understanding of the genes and pathways involved in determining root system architecture in response to both intrinsic and extrinsic (environmental) response pathways, and provides a brief overview of the latest root system phenotyping technologies and their potential impact on elucidating the genetic control of root development in plants.
Control of graft-versus-host disease with maintenance of the graft-versus-leukemia effect in a murine allogeneic transplant model using retrovirally transduced murine suicidal lymphocytes.

Objective Limited clinical trials have validated the hypothesis of controlling graft-versus-host disease (GVHD) arising from stem cell transplant utilizing suicidal T-lymphocytes that have been transduced to express the HSV-TK gene. However, clinical utility has been limited by diminished T-cell function arising from the production process. To evaluate strategies for harnessing the graft-versus-leukemia (GVL) effect while improving the safety and function of suicidal lymphocytes, we have developed techniques to produce fully functional, retrovirally transduced, HSV-TK –positive murine T cells (TK + TC). Methods Utilizing a murine major histocompatibility complex–matched transplant model, we evaluated the ability of TK + TC to generate a GVL effect and the ability to control GVHD in experiments where we varied the dose of TK + TC, ganciclovir (GCV) dose, the start of GCV administration (day 4, 7, 10, 13, 15, or 19) posttransplantation, and the GCV administration route (osmotic pump versus intraperitoneal). Results At TK + TC doses in excess of the standard lethal dose (SLD) of unmanipulated T-cells, GCV administration completely (2 × SLD) and partially (4 × SLD) controlled GVHD. Additionally, GVHD remained reversible despite delaying administration of GCV for a week after GVHD developed. Importantly, GVHD was controlled with a 1-log but not 2-log reduction in GCV dose, and this "partial suicide" preserved more circulating TK + TC compared with standard-dose GCV. Survival of leukemia-positive mice receiving TK + TC and GCV was significantly increased compared with control cohorts not receiving GCV or transplanted with unmanipulated T cells, thereby demonstrating a GVL effect. Conclusion Retrovirally transduced suicidal lymphocytes generate a potent GVL effect while simultaneously enabling control of GVHD, which results in improved leukemia and GVHD-free survival.
Enhanced abdominal aortic aneurysm in TIMP-1-deficient mice.

Background Matrix metalloproteinases (MMPs) are known elastolytic mediators of abdominal aortic aneurysm (AAA) degeneration, and their activity is tightly regulated by the presence of tissue inhibitors of MMPs (TIMPs). Imbalances in this system may be instrumental in compromising arterial wall integrity. The aim of this study was to show that, in an elastase-induced murine model of aneurysm formation, TIMP-1 has a protective effect. Materials and methods Twenty-four wild-type (TIMP-1 +/+ ) and 22 knockout (TIMP-1 −/− ) mice underwent laparotomy and isolation of the infrarenal aorta. A polyethylene catheter was inserted into the aorta and dilute pancreatic elastase (0.39 Units/ml) was infused over 5 min using a perfusion pump. Pre- and postinfusion maximal aortic diameters were obtained in triplicate for each animal using NIH Image. Final aortic measurements were obtained 14 days later, prior to perfusion fixation with 10% buffered Formalin. Aortic specimens were sectioned and stained. Statistical analysis was performed using the Student’s t test. Results TIMP-1 −/− mice demonstrated a significant postinfusion diameter increase compared to wild-types after elastase, which was not seen after saline infusion. At sacrifice, TIMP-1 −/− mice, following both saline and elastase infusion, showed a significant increase in maximal aortic diameter relative to postinfusion measurements compared to TIMP-1 +/+ mice. Conclusions TIMP-1 −/− mice develop larger aneurysms than TIMP-1 +/+ mice. This study illustrates the protective effects of TIMP-1 in an experimental AAA model and may provide a means for pharmacologically controlling aneurysm growth.
T Cells and Blood Vessels Costimulation Turns Up the Pressure

Remarkable advances in our understanding of innate and adaptive immunity have shed light on why inflammation is centrally involved in the pathogenesis of many diseases traditionally not viewed as primarily inflammatory in nature. One key area of progress has been the discovery and study of innate immune receptors, referred to as pattern recognition receptors (PRRs), such as toll-like receptors and nod-like receptors. PRRs recognize molecules commonly produced by microbial pathogens, broadly defined as pathogen associated molecular patterns (PAMPs), but PRRs also recognize self molecules that are indicators of cell injury or death. These self molecules, called damage-associated molecular patterns (DAMPs), include reactive oxygen species, intracellular crystalline deposits, normal molecules in abnormal locations (ATP, heat shock proteins, nuclear proteins), and many others.1,2 DAMPs may be induced or change location because of cell injury or death by any number of causes (genetic, traumatic, toxic, metabolic), and their recognition by innate immune system receptors will initiate responses that include local and systemic inflammation. This is why diseases with just about any underlying cause may be expected to have an inflammatory component. Importantly, the innate immune system has evolved to amplify and modify responses to best combat diverse infections, but these amplified and specialized responses, if inappropriately targeted against self, may themselves become intrinsic to the progression of disease processes. One way this can occur is by innate immune stimulation of adaptive immune responses mediated by T lymphocytes. In fact, normal protective T cell-mediated immunity requires a kick-start by the innate immune system, a condition that ensures that we do not readily mount powerful and potentially harmful adaptive immune responses when there is no real damage or danger present. Article see p 2529 One of major ways in which innate immunity promotes T cell-mediated immunity is through the activation of antigen-presenting …
Extremely-scaled double-gate CMOS with non-self-aligned back gate

This paper presents the possibly viable concept of extremely-scaled but non-self-aligned planar DG CMOS technology that, irrespective of moderate back-gate underlap, can still yield high performance and low leakage with good control of short-channel effects (SCEs). The pragmatic design exploits the inherent beneficial features of both asymmetrical and symmetrical DG FETs as presented in H.S.P Wong et al. (1994), H. Hanafi et al. (2003), E. J. Nowak et al. (2004) and K. Kim and J. G. Fossum (2001), as well as the flexibility in their structural design. Off-state current (l/sub off/) reduction by reverse back-gate bias in DG device is studied and compared with the reverse body bias based in A. Keshavarzi et al. (2001) in bulk-Si counterpart.
Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream caspase activation to overcome apoptotic resistance in MCF-7 breast adenocarcinoma cells

Febrile hyperthermia enhanced TNF-stimulated apoptosis of MCF-7 cells and overcame resistance in a TNF-resistant, MCF-7 variant (3E9), increasing their TNF-sensitivity by 10- and 100-fold, respectively. In either cell line, the hyperthermic potentiation was attributable to increased apoptosis that was totally quenched by caspase inhibition. In MCF-7 cells, hyperthermic potentiation of apoptosis was associated with sustained activation of upstream caspases in response to TNF and more prominent engagement of the intrinsic apoptotic pathway. Apoptotic enhancement by hyperthermia was primarily mediated by caspase-8 activation, as the specific inhibitor, Z-IETD, blocked cell death, whereas direct engagement of the intrinsic apoptotic pathway (with doxorubicin) was not affected. In 3E9 cells, hyperthermia alone induced activation of caspase-8, and was further enhanced by TNF. In 3E9 cells, hyperthermia caused TNF-dependent loss of mitochondrial membrane potential and activation of capspase-9 that was initiated and dependent on upstream caspases. MCF-7 and 3E9 cells were equally sensitive to exogenous C(6)-ceramide, but mass spectroscopic analysis of ceramide species indicated that total ceramide content was not enhanced by TNF and/or hyperthermia treatment, and that the combination of TNF and hyperthermia caused only modest elevation of one species (dihydro-palmitoyl ceramide). We conclude that febrile hyperthermia potentiates apoptosis of MCF-7 cells and overcomes TNF-resistance by sustained activation of caspase-8 and engagement of the intrinsic pathway that is independent of ceramide flux. This report provides the first evidence for regulation of caspase-dependent apoptosis by febrile hyperthermia.
Co-Con: Coordinated control of power and application performance for virtualized server clusters

Today's data centers face two critical challenges. First, various customers need to be assured by meeting their required service-level agreements such as response time and throughput. Second, server power consumption must be controlled in order to avoid failures caused by power capacity overload or system overheating due to increasing high server density. However, existing work controls power and application-level performance separately and thus cannot simultaneously provide explicit guarantees on both. This paper proposes Co-Con, a novel cluster-level control architecture that coordinates individual power and performance control loops for virtualized server clusters. To emulate the current practice in data centers, the power control loop changes hardware power states with no regard to the application-level performance. The performance control loop is then designed for each virtual machine to achieve the desired performance even when the system model varies significantly due to the impact of power control. Co-Con configures the two control loops rigorously, based on feedback control theory, for theoretically guaranteed control accuracy and system stability. Empirical results demonstrate that Co-Con can simultaneously provide effective control on both application-level performance and underlying power consumption.
Jigsaw Puzzles and River Banks: Two Ways of Picturing Our Future

The papers presented at the 2004 Academy meetings can be thought of as pieces from jigsaw puzzles. While the employment of this metaphor over the years has been useful, we may be ready for a new image, one that is both more accurate and inspiring. We can picture ourselves working at different locations along a river bank. Some of us work upstream, near the headwaters, at the molecular and genetic level. Others work on anatomy, physiology, culture, psychological well-being, ethics, and even spirituality—all different places along the shore as we move down the river toward the broad and deep waters by the bay. But no matter what our location, we all work on water in one form or another. This forces us to come to grips with our interdependence as researchers and with far more complex notions of causation that have been popular heretofore. The riverbank metaphor promises a kind of cooperation, unity, and mutual appreciation that cannot be gained when we come to interdisciplinary meetings carrying our independ...
Medical Expenditure Growth and The Diffusion of Medical Technology

The general consensus among health economists is that the increasing capability of medical providers— often called medical “technology”—is responsible for the majority of growth in medical expenditure. And yet, the principle means of understanding medical technology is through the use of total factor productivity, which, despite giving reasonable estimates of the magnitude of the effects, is not a theory of technology, leaving policymakers without effective tools for prediction. This paper develops a descriptive model of technology that may have interesting implications for health economics. The model suggests that the manner of diffusion of technology is critical, and when technology diffuses haphazardly, the effects on expenditure can be unexpectedly large.
Haemophilus ducreyi Inhibits Phagocytosis by U-937 Cells, a Human Macrophage-Like Cell Line

Haemophilus ducreyi is a gram-negative obligate human pathogen that causes the genital ulcer disease chancroid. Chancroid lesions are deep necrotic ulcers with an immune cell infiltrate that includes macrophages. Despite the presence of these phagocytic cells, chancroid ulcers can persist for months and live H. ducreyi can be isolated from these lesions. To analyze the interaction of H. ducreyi with macrophages, we investigated the ability of H. ducreyi strain 35000 to adhere to, invade, and survive within U-937 cells, a human macrophage-like cell line. We found that although H. ducreyi strain 35000 adhered efficiently to U-937 cells, few bacteria were internalized, suggesting that H. ducreyi avoids phagocytosis by human macrophages. The few bacteria that were phagocytosed in these experiments were rapidly killed. We also found that H. ducreyi inhibits the phagocytosis of a secondary target (opsonized sheep red blood cells). Antiphagocytic activity was found in logarithmic, stationary-phase, and plate-grown cultures and was associated with whole, live bacteria but not with heat-killed cultures, sonicates, or culture supernatants. Phagocytosis was significantly inhibited after a 15-min exposure to H. ducreyi, and a multiplicity of infection of approximately 1 CFU per macrophage was sufficient to cause a significant reduction in phagocytosis by U-937 cells. Finally, all of nine H. ducreyi strains tested were antiphagocytic, suggesting that this is a common virulence mechanism for this organism. This finding suggests a mechanism by which H. ducreyi avoids killing and clearance by macrophages in chancroid lesions and inguinal lymph nodes.
The MARKOV EXPERT for finding episodes in time series

Summary form only given. We describe a domain-independent unsupervised algorithm for segmentation of time series data into meaningful episodes, focusing on the problem of text segmentation. The VOTING EXPERTS algorithm of Cohen et al. (2002) achieves results with fairly low rates of error by combining two experts that analyze the input's frequency and entropy patterns. The MARKOV EXPERT is a new approach that improves the performance of VOTING EXPERTS by further refining those results with votes from an additional expert. The new expert applies a method inspired by Teahan et al.'s (2000) compression-based approach for Chinese text. Their supervised approach requires a large, correctly segmented training corpus. Segmentation of the input is modeled as a Markov process, with spaces inserted such that the resulting string is smallest under PPM compression with respect to the corpus. In the unsupervised setting, external corpuses are not available. Thus, we draw event pattern data from a new corpus constructed by generating a preliminary segmentation using the original VOTING EXPERTS. Since VOTING EXPERTS finds episode boundaries fairly well (precision and recall around 77% and 75%), the quality of this new corpus is sufficient to allow the MARKOV EXPERT to further improve results significantly. The MARKOV EXPERT votes on possible boundaries by accumulating votes within a sliding window that moves over the input. The context within each window is compared to the corpus using a segmentation utility function. Quality of a particular segmentation is positively correlated to the frequency of the resulting suffixes and prefixes in the corpus, and negatively correlated to instances in which the current context appears intact within a word in the corpus.
Clinicopathological features of prostate cancers detected after an initial diagnosis of 'atypical glands suspicious for cancer'

Background: A diagnosis of ‘atypical glands suspicious for cancer’ (ATYP) in prostate needle biopsy is associated with approximately a 40–50% risk of detecting prostate cancer in subsequent biopsies. Pathological characteristics of prostate cancer following an initial diagnosis of ATYP are rarely studied.Design: We studied prostate biopsies with an initial diagnosis of ATYP. Number of ATYP foci, presence of concomitant high grade prostatic intraepithelial neoplasia (HGPIN), date and diagnosis of repeat biopsies were recorded. When radical prostatectomy was performed for confirmed prostate cancer, Gleason score, tumour volume, extraprostatic extension, seminal vesicle invasion, lymph node status, and surgical margins of resection status were also recorded.Results: Between 1992 and 2009, 239 patients biopsied at our institution carried a diagnosis of ATYP and underwent repeat follow-up biopsies. The mean time interval between first biopsy and last repeat biopsy was 14.4 months; the average number of follow ...
Identity technologies: constructing the self online

This book examines different ways individuals construct their identities online. The editors bring together research occurring in a number of fields to address the question of what being online, an...
An Iml3-Chl4 Heterodimer Links the Core Centromere to Factors Required for Accurate Chromosome Segregation

SUMMARY Accurate segregation of genetic material in eukaryotes relies on the kinetochore, a multiprotein complex that connects centromeric DNA with microtubules. In yeast and humans, two proteins—Mif2/ CENP-C and Chl4/CNEP-N—interact with specialized centromeric nucleosomes and establish distinct but cross-connecting axes of chromatin-microtubule linkage. Proteins recruited byChl4/CENP-Ninclude a subset that regulates chromosome transmission fidelity. We show that Chl4 and a conserved member of this subset, Iml3, both from Saccharomyces cerevisiae, form a stable protein complex that interacts with Mif2 and Sgo1. We have determined the structures of an Iml3 homodimer and an Iml3-Chl4 heterodimer, which suggest a mechanism for regulating the assembly of this functional axis of the kinetochore. We propose that at the core centromere, the Chl4-Iml3 complex participates in recruiting factors, such as Sgo1, that influence sister chromatid cohesion and encourage sister kinetochore biorientation.
Measurements of pH by Glass Microelectrodes

Both electrodes (Rector et al., 1965; Vieira and Malnic, 1968) and dye indicators (Rector and Carter, 1963) have been used for the measurement of in vivo intraluminal pH of the nephron. Electrodes used for the measurement of pH have been of the antimony (Vieira and Malnic, 1968) and hydrogen ion (H+) sensitive glass types. In our laboratory, two different types of H+ sensitive glass electrodes have been miniaturized to the extent that they can be used for direct in vivo measurement of intraluminal pH in the typical micropuncture preparation (Carter et al., 1967a; Pucacco and Carter, 1976). The newest of these electrodes (Pucacco and Carter, 1976) has also been used in our laboratory to measure pH in the microenvironment of the isolated tubule preparation.
The Estrous Cycle in Cattle: Physiology, Endocrinology, and Follicular Waves12

Abstract Estrous synchronization is a valuable tool to enhance reproductive management in beef cattle. Procedures that facilitate synchronization of estrus in cycling cattle and induce ovulatory estrus in peripubertal heifers and postpartum anestrous cows will increase reproductive rates and expedite genetic progress through use of AI. A better understanding of physiology and endocrinology of the estrous cycle will improve reproductive management of beef cattle and facilitate the successful application of estrous synchronization protocols, which, in turn, will increase the use of AI and hasten genetic improvement in beef cattle production systems. Effective reproductive management requires the successful application of available knowledge to current estrous synchronization protocols. To that end, this review covers the basic physiology and endocrinology of the estrous cycle and provides an overview of our current understanding of follicular waves. Topics to be covered include endocrinology associated with the estrous cycle, follicular development, and the corpus luteum. A review of the utilization of estrous synchronization and AI in the U. S. beef industry is also briefly discussed.
DIPA-family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia.

p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, whereas p120-1A takes precedence in neurons, fibroblasts, and macrophages. During epithelial-to-mesenchymal transition, E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101–amino acid “head domain” comprising the p120-1A N-terminus. Although its exact role is unknown, the head domain likely mediates developmental and cancer-associated events linked to p120-1A expression (e.g., motility, invasion, metastasis). Here we identified delta-interacting protein A (DIPA) as the first head domain–specific binding partner and candidate mediator of isoform 1A activity. DIPA colocalizes with AJs in a p120-1A- but not 3A-dependent manner. Moreover, all DIPA family members (Ccdc85a, Ccdc85b/DIPA, and Ccdc85c) interact reciprocally with p120 family members (p120, δ-catenin, p0071, and ARVCF), suggesting significant functional overlap. During zebrafish neural tube development, both knockdown and overexpression of DIPA phenocopy N-cadherin mutations, an effect bearing functional ties to a reported mouse hydrocephalus phenotype associated with Ccdc85c. These studies identify a novel, highly conserved interaction between two protein families that may participate either individually or collectively in N-cadherin–mediated development.
The Human Dimensions of Desertification

This special issue on desertification grew out of a survey of the human causes and consequences of desertification sponsored by the United Nations Environment Program and the United Nations Fund for Population Activities. The basic group of contributors to this volume of 19 essays are geographers, but the viewpoints of other disciplines and data generated by their research activities are well represented. The initial cluster of essays measures the extent and identifies the process of desertification. A second group of profiles demonstrates the impact of desertification on a human scale. The final cluster examines the prospect for coping with desertification in the future, the experience gained thus far, and some of the creative alternatives that might be employed in the struggle against desertification.
Multi-population genetic algorithm in multiobjective fuzzy and flexible Job Shop scheduling

It was difficult to obtain the optimal solution in multiobjective fuzzy flexible Job Shop scheduling by using common genetic algorithms.To solve this problem,based on the consideration of due date obeyed fuzzy time window distribution,a multiobjective fuzzy flexible Job Shop scheduling model was presented.It was aimed at maximize customer satisfaction and minimize completion time.Besides,crossbar collaborative multi-group genetic algorithm was proposed.In this algorithm,multiple initial populations were generated based on process and machine two layers coding mode.And then,migration and sharing of excellent individuals was achieved by competition among various groups.The simulation results of three classical Job Shop scheduling problems and instance demonstrated that the proposed algorithm could effectively overcome the stagnation and improve global search capability.Comparing to other algorithms,the optimal solution or near optimal solution obtained by the proposed algorithm was better.
A chemical test for pregnancy applied to the determination of estrin in the urine of normal and toxemic patients in the last trimester of pregnancy: II. Application of a short chemical method; and administration of theelin in late toxemias of pregnancy

Abstract 1. 1. Further data are presented showing a definitely lowered level of estrin excretion in the urine in a series of cases of the late toxemias of pregnancy. 2. 2. A short chemical procedure for detecting estrin in urine has been developed and was applied to the analysis of all specimens in this series. A test by this method may be completed in four hours. 3. 3. Pre-eclampsia, eclampsia, and chronic nephritis complicating pregnancy are considered the late toxemias of pregnancy. 4. 4. Fifty-eight patients in the last trimester of their pregnancies were carefully studied clinically and complete twenty-four-hour urine specimens were examined for estrin. Estrin excretion expressed as “ferric chloride numbers” (F. N.) gave averages: for 6 normal cases, 87.16, for 26 patients with chronic nephritis complicating pregnancy, 47.05; and for 26 cases of pre-eclampsia, 40.03. 5. 5. In this series normal cases have been sharply delimited from the toxemic groups on the basis of estrin excretion. No cases of true eclampsia appear in this series. 6. 6. As concerns estrin excretion the line of demarcation between chronic nephritis complicating pregnancy and pre-eclampsia is not as sharp as in our former series in which the original procedure was used. 7. 7. Nine patients received 10,000 international units of theelin intramuscularly on each of 3 successive days, and complete twenty-four-hour urine specimens on each of these days from each patient were examined for estrin (Chart 1). 8. 8. No accurate conclusions may be drawn from this series concerning estrin excretion in the late toxemias of pregnancy following the intramuscular administration of theelin. 9. 9. It is possible that the short average duration of labor in the 9 patients treated with theelin may have been the result of this therapy. 10. 10. In the cases of late toxemias of pregnancy in this series to whom theelin was administered, in the dosage and in the manner herein described, no improvement was found which could be directly ascribed to the hormone therapy.
Logics of Redistribution: Determinants of Generosity in Three U.S. Social Welfare Programs

Social policy scholars disagree about which factors best predict U.S. welfare state generosity. We argue that this disagreement is an artifact of study designs. Researchers usually study either the totality of a state’s social expenditures or one specific program. These approaches overlook the fact that individual social programs were born of different circumstances and serve different constituencies. Comparing state-level policies for Temporary Assistance for Needy Families (TANF), the Children’s Health Insurance Program (CHIP), and the Supplemental Nutrition Assistance Program (SNAP), our findings suggest that these programs are governed by distinct logics of redistribution. Racial characteristics drive TANF generosity. Economic forces best predict CHIP generosity. SNAP generosity is a function of political factors. Qualitative data from Congressional hearings confirm these findings. These results adjudicate between conflicting accounts of the contemporary welfare state and also highlight which aspects ...
Crossed Opinions: The Elizabethan Years

A dozen years before Elizabeth acceded to the English throne, John Heywood’s Dialogue of Proverbs (1546) offered the following couplet as an instance of common-sense scepticism regarding inductions about human character: Ye knowe what he hath been (quoth he) but ywis, Absence saieth playnely, ye knowe not what he is. Half a century later, in Hamlet, Shakespeare gave Ophelia a strikingly similar speech: ‘Lord, we know what we are, but know not what we may be’ (4.5.42–3). It is thus evident that English proverbial wisdom in the sixteenth century could readily cast doubt on presumptions about human identity in a mutable world. The very fact that such doubt finds transmission through proverbial expression lends support to the idea that a lay scepticism pre-dated any manifestation of philosophical scepticism in early modern Britain. One is tempted to suggest that such fundamental doubt is ahistorical — that it appears under any circumstances, in any culture. And this may be true. What we see in late Elizabethan England, however, is that common-sense doubt quickly combines with the Socratic Nihil scio, lending proverbial scepticism a philosophic inflection. Thus Marston laces his plays with such remarks as ‘I know I nothing know’ and ‘The more I learnt the more I learnt to doubt’.1
Impact and Duration of Brief Surgeon-Delivered Smoking Cessation Advice on Attitudes Regarding Nicotine Dependence and Tobacco Harms for Patients with Peripheral Arterial Disease

Background Despite the recognized benefits of smoking cessation, many clinicians question if a brief smoking cessation intervention can help dedicated smokers with peripheral arterial disease understand nicotine dependence and harms related to smoking. We investigated the impact and durability of a multimodal smoking cessation intervention on patient attitudes regarding nicotine dependence and the health effects of smoking. Methods We conducted a pilot cluster-randomized trial of a brief smoking cessation intervention at 8 vascular surgery practices between September 1, 2014 and August 31, 2015. Compared with control sites, patients at intervention sites received protocolized brief cessation counseling, medications, and referrals to a quitline. After their clinic visit and again at 3 months, participants completed a brief survey about patient attitudes regarding nicotine dependence and the health effects of smoking. Responses to questions were analyzed using chi-squared test and Student's t-test. Results All trial participants (n = 156) complete the initial survey, and 75 (45%) participants completed the follow-up survey. Intervention and control patients both reported a greater than 30-pack-year history (80% vs. 90%, P = 0.07) and previous failed quit attempts (77% vs. 78%, P = 0.8). Compared with usual care, patients in the intervention group were more likely to describe hearing advice to quit from their surgeon (98% vs. 77%, P < 0.001), and expressed “a lot” or “some” interest in quitting (95.4% vs. 85.7%, P = 0.05). Patients in the intervention group were also more likely to acknowledge their addictive behaviors, consistently scoring higher on question bank items regarding nicotine addiction (52.9 vs. 48.0, P = 0.006) and the negative health effects of smoking (scaled score 56.6 vs. 50.6, P = 0.001). When resurveyed 3 months after intervention, patients in the intervention group had larger declines in nicotine dependence and health effect domains, suggesting durable impact of the intervention on patient attitudes regarding nicotine addiction and smoking harms. Conclusions Brief smoking cessation counseling by a vascular surgeon increases patient interest in smoking cessation and awareness of smoking harms, and this effect was durable 3 months after intervention. This evidence suggests that even brief counseling within a surgical clinic has the potential to impact patient desire to quit.
On the role of acetylcholine in the mechanism of nerve activity.

Publisher Summary This chapter discusses the role of acetylcholine (ACh) in the mechanism of nerve activity. Acetylcholine, supposedly a neurohumoral transmitter, is a compound effective in amounts of the same order of magnitude as vitamins or hormones. The concentration of Ch. E. is high in all nerve fibers but rises higher in the synaptic region. This is particularly conspicuous in nonmyelinated fibers. Direct evidence for the localization of Ch. E. at the neuronal surface has been offered with experiments on the giant axon of the squid. The polarized state of the membrane is due to a selective permeability to K ions, which are present in different concentrations on the two sides of the membrane. Any stimulus acting on the cell surface causes the local breakdown of resistance and increased permeability to all ions. The membrane becomes depolarized, the resting potential disappears or may be even reversed. It is found that if the release of ACh and its subsequent breakdown are responsible for the alterations of the nerve membrane, chemical reactions must supply the energy for the resynthesis of ACh in the recovery process.
Dissociable effects of the kappa opioid receptor agonist nalfurafine on pain/itch-stimulated and pain/itch-depressed behaviors in male rats.

Nalfurafine is a G protein signaling-biased kappa opioid receptor (KOR) agonist approved in Japan for second-line treatment of uremic pruritus. Neither nalfurafine nor any other KOR agonist is currently approved anywhere for treatment of pain, but recent evidence suggests that G protein signaling-biased KOR agonists may have promise as candidate analgesics/antipruritics with reduced side effects compared to nonbiased or s-arrestin-signaling-biased KOR agonists. This study compared nalfurafine effects in rats using assays of pain-stimulated and pain-depressed behavior used previously to evaluate other candidate analgesics. Nalfurafine effects were also examined in complementary assays of itch-stimulated and itch-depressed behavior. Intraperitoneal lactic acid (IP acid) and intradermal serotonin (ID 5HT) served as noxious and pruritic stimuli, respectively, in male Sprague Dawley rats to stimulate stretching (IP acid) or scratching (ID 5HT) or to depress positively reinforced operant responding in an assay of intracranial self-stimulation (ICSS; both stimuli). Nalfurafine was equipotent to decrease IP acid-stimulated stretching and ID 5HT-stimulated scratching; however, doses of nalfurafine that decreased these pain/itch-stimulated behaviors also decreased control ICSS performance. Moreover, nalfurafine failed to alleviate either IP acid- or ID 5HT-induced depression of ICSS. These results suggest that nalfurafine-induced decreases in pain/itch-stimulated behaviors may reflect nonselective decreases in motivated behavior rather than analgesia or antipruritus against the noxious and pruritic stimuli used here. This conclusion agrees with the absence of clinical data for nalfurafine analgesia and the weak clinical data for nalfurafine antipruritus. Nalfurafine bias for G protein signaling may not be sufficient for clinically safe and reliable analgesia or antipruritus.
Research on Cognitive, Personality, and Social Psychology: II

This account is the second of two chapters addressing a portion of the ETS research on cognitive, personality, and social psychology conducted since the organization’s inception. The topics covered include, in cognitive psychology, creativity; in personality psychology, cognitive styles and kinesthetic aftereffect; and in social psychology, risk taking.
Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR.

Abstract Objectives Activation of the bile acid (BA) receptors farnesoid X receptor (FXR) or G protein-coupled bile acid receptor (GPBAR1; TGR5) improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods Wild-type (WT), Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα) as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP) whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders.
Reframing the Dominant Diversity Discourse: Alternate Conversations for Creating Whole System Change.

Diversity and inclusion (D&I) efforts in higher education are decades old, yet progress continues to be slow and elusive for many campuses. Recent events in colleges and universities across the United States suggest that long-standing challenges related to access, equity and inclusion remain as entrenched and intractable as they have ever been, resulting in campus environments that may be unwelcoming or hostile to faculty, staff and students from underrepresented groups. One reason for the partial success of university D&I programs is that they overemphasize individual actors, attitudes and behaviors while neglecting the systemic, organizational cultures in which those actors reside. Drawing on the organization development and change literatures, this paper offers three alternate perspectives for reframing campus diversity work, arguing that all D&I initiatives must consider the 1) contextual, 2) multilevel and 3) systemic nature of change if they are to be robust and successful.
New Developments in the Definition and Diagnosis of Autism

There is no way to discuss the diagnosis and definition of psychopathology without first surveying the confusion surrounding these issues. There are few conferences, symposia, and colloquia of mental health professionals in which diagnostic issues are not discussed and disputed. The similarities among these diagnostic disputes do not prevent them from being repeated regularly. A great range of attitudes toward diagnostic classification can be found among researchers and clinicians. Some have devoted their careers to demonstrating the validity of a particular diagnostic category. Others have met in committees and professional groups in order to categorize the entire field of mental disorders. There are still others who believe that diagnostic labeling should be abandoned all together. They think it condemns human beings to arbitrary pigeonholes and results in restrictive and stereotype treatment. Most of all, it is extremely difficult not to have mixed feelings about the diagnostic classification process. It touches on so many of our basic interests and professional activities that we are drawn into the confusion whether we like it or not.
Risk of hepatic events in patients treated with vancomycin in clinical studies: a systematic review and meta-analysis.

Background: Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events.
Why do depressed people prefer sad music

One of the cardinal symptoms of major depressive disorder (MDD) is persistent sadness. Do people with MDD actually prefer sad stimuli, potentially perpetuating their depression? Millgram, Joormann, Huppert, and Tamir (2015) observed such preferences and interpreted them as reflecting a maladaptive emotion regulatory goal to upregulate sad feelings. We assessed emotional music choice among both those with MDD and healthy controls (HC), and assessed the reasons for music preferences in these two groups. Seventy-six female participants (38 per group) completed two tasks: (1) Millgram et al.'s (2015) music task wherein participants listened to happy, neutral, and sad music excerpts and chose the one they wanted to listen to most, and (2) a novel Emotional Music Selection Task (EMST) wherein participants chose preferred music clips, varying in emotion and energy level, in paired-choice trials. In the replication music task, MDD people were more likely to choose sad music. However, inconsistent with any motivation to upregulate sadness, people with MDD reported that they chose sad music because it was low in energy levels (e.g., relaxing). EMST results revealed that MDD people had a stronger preference for both low energy and sad music, relative to HC. The strong appeal of sad music to people with MDD may be related to its calming effects rather than any desire to increase or maintain sad feelings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
My Mother the Car (or Why It's a Bad Idea to Give Your Car a Personality)

What happens when we endow an autonomous vehicle with a personality? It sounds like a good idea—witty banter, friendly advice, and encouragement from your car. But science fiction writers predicted this technology and both the good and bad scenarios that could arise. A brief sample of some of these situations from American television and film is enlightening but suggests that granting a personality to an auto is ill-advised. This theme issue explores the state and potential benefits and ethical dilemmas of connected and autonomous vehicles. While fully autonomous vehicles are already experimentally deployed, they will become ubiquitous within a few years. Soon after we should see an experimental deployment of vehicles that have a level of artificial intelligence such that they could be considered “sentient” (self-aware) or even “anthropomorphic” (human-like). These vehicles could do much more than self-drive or give us driving advice, travel information, and various forms of infotainment. They could also remind us of important stops to be made, listen to our complaints about traffic and other drivers, and even provide us with soothing advice. And this advice could be given with the benefit of an artificial personality—one that could be formal, friendly, or even replicates that of a famous person, celebrity, or a loved one.
The candle seesaw

A candle skewered transversely near its center of mass by a needle and balanced between two low-friction supports, when lit on both ends, will drip asymmetrically and begin to oscillate like a seesaw; these oscillations grow in time. We examine the onset of instability, and find that the candle does not oscillate quasi-stably until the vertical center of mass is lowered by the symmetrical melting of each end, creating a physical pendulum with a well-defined characteristic period. Additional asymmetric dripping below horizontal drives the pendulum, leading to linear growth in amplitude. The drop release becomes phase locked to the seesaw motion of the candle. We develop a small-angle analytical model that predicts the maximum growth rate when the dripping rate matches the seesaw frequency. Measurements of the motion, droplet phase, and melting rate confirm the validity of the model. We compare our results to earlier studies and make suggestions for the demonstrator.
Interval estimation for linear functions of medians in within‐subjects and mixed designs

The currently available distribution-free confidence interval for a difference of medians in a within-subjects design requires an unrealistic assumption of identical distribution shapes. A confidence interval for a general linear function of medians is proposed for within-subjects designs that do not assume identical distribution shapes. The proposed method can be combined with a method for linear functions of independent medians to provide a confidence interval for a linear function of medians in mixed designs. Simulation results show that the proposed methods have good small-sample properties under a wide range of conditions. The proposed methods are illustrated with examples, and R functions that implement the new methods are provided.
A patient-centric liquid chromatography-tandem mass spectrometry microsampling assay for analysis of cannabinoids in human whole blood: Application to pediatric pharmacokinetic study

Abstract Medical cannabis is increasingly used for the treatment of various ailments in children and adults. Three major cannabinoids in cannabis are delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). There is a growing need to develop and utilize a patient-centric blood microsampling methodology to enable clinical trials and facilitate therapeutic drug monitoring. We have employed the volumetric absorptive microsampling (VAMS™) devices that enables accurate and precise collection of a fixed volume (20 µL) of blood, minimizing the impact of hematocrit on accurate quantitation. We developed an ultra-performance liquid chromatographic method with tandem mass spectrometry detection for the quantification of three cannabinoids (THC, CBD, and CBN) employing deuterium labelled internal standards (THC-D3, CBD-D3, and CBN-D3). Sample extraction of VAMS™ devices, followed by solid phase extraction, reverse phase chromatographic separation, and selective detection using tandem mass spectrometry with a 6-minute runtime per sample was developed. Standard curves were linear between 1 and 500 ng/mL for THC and 0.5–500 ng/mL for CBD and CBN. Intra-day accuracies were within 91.3–112% while inter-day accuracies were within 94.4–107% with both having precisions (CV (%)) of
L’Assommoir ou les déboires du premier objet

This essay draws on Melanie Klein’s psychoanalytical theories to demonstrate that the world of Zola’s L’Assommoir may be read as the actualization of the mental phantasies that inhabit the psyche o...