cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5096: Targeted ablation of essential oncogenes in rhabdomyosarcoma with CRISPR/Cas9 gene therapy

Targeted therapy seeks to exploit unique vulnerabilities in cancer cells not present in normal tissue. The development of effective therapies targeting essential tumor proteins has had significant challenges particularly for tumor oncogenes many of which have proven “undruggable”. Targeting these critical tumor oncogenes has been one of the foremost challenges in cancer research. Current sequencing technology facilitates rapid identification of novel cancer mutations yet there are no effective therapeutic strategies aimed at targeting essential cancer genes at the genome level. To overcome the challenges associated with targeting “undruggable” cancer proteins, we have employed high efficiency CRISPR/Cas9 genome editing technology to destroy cancer cells by directly targeting the genomic DNA of essential cancer genes. We used pediatric rhabdomyosarcoma to demonstrate the potential of CRISPR/Cas9 gene therapy in solid tumor preclinical xenograft mouse models. Rhabdomyosarcoma is an aggressive pediatric sarcoma characterized by myogenic differentiation arrest. The two major subtypes of rhabdomyosarcoma (RMS), embryonal (ERMS) and alveolar (ARMS) are defined largely by either activation of the RAS pathway (ERMS) or the presence of a fusion oncogene between PAX3 and FOXO1 (ARMS). CRISPR/Cas9 was first used to target critical exons in the activated RAS or PAX3/FOXO1 oncogenes unique to each RMS subtype, using inducible or viral CRISPR delivery systems. Targeting these essential genes resulted in significant regression of tumor xenografts due to a combination of cell death and differentiation. By precisely targeting the activating mutations in the RAS oncogene or the fusion site in the PAX3/FOXO1 fusion gene we further demonstrate that tumor-specific CRISPR/Cas9-mediated gene therapy can also be achieved. This strategy disrupts the essential cancer oncogenes with minimal impact to normal cells that do not harbor the unique cancer mutations. Our results highlight the utility of exploiting essential cancer genetic mutations for personalized therapy. This novel approach to cancer therapy provides a potential alternative strategy for targeting “undruggable” oncogenes while establishing a foundation for further development of CRISPR/Cas9 gene therapy for cancer treatment Citation Format: Michael Phelps, Heechang Yang, Eleanor Chen. Targeted ablation of essential oncogenes in rhabdomyosarcoma with CRISPR/Cas9 gene therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5096. doi:10.1158/1538-7445.AM2017-5096
Security Glitches: The Failure of the Universal Camouflage Pattern and the Fantasy of “Identity Intelligence”

Focusing on the paradoxes revealed in the multibillion dollar mistake of the Universal Camouflage Pattern (UCP) and the expansive ambit of a leaked National Security Agency briefing on its approach...
War, Sleep and PTSD War, and War-Related Trauma: An Overview

Throughout history, times of massive destruction create an atmosphere of chaos that compels individuals to face the terror of unanticipated injury, loss, and death. During natural or man-made disasters, war, and acts of terror, psychological injury may occur on its own or in conjunction with physical injury. This psychological trauma may occur following exposure to the injury and death of others, the disruption of the physical environment, or as a consequence of the terror and helplessness that these events combine to evoke.
Probing the Mechanism of Receptor Activity-Modifying Protein Modulation of GPCR Ligand Selectivity through Rational Design of Potent Adrenomedullin and Calcitonin Gene-Related Peptide Antagonists.

Binding of the vasodilator peptides adrenomedullin (AM) and calcitonin gene–related peptide (CGRP) to the class B G protein–coupled receptor calcitonin receptor–like receptor (CLR) is modulated by receptor activity–modifying proteins (RAMPs). RAMP1 favors CGRP, whereas RAMP2 and RAMP3 favor AM. Crystal structures of peptide-bound RAMP1/2-CLR extracellular domain (ECD) heterodimers suggested RAMPs alter ligand preference through direct peptide contacts and allosteric modulation of CLR. Here, we probed this dual mechanism through rational structure-guided design of AM and CGRP antagonist variants. Variants were characterized for binding to purified RAMP1/2-CLR ECD and for antagonism of the full-length CGRP (RAMP1:CLR), AM1 (RAMP2:CLR), and AM2 (RAMP3:CLR) receptors. Short nanomolar affinity AM(37–52) and CGRP(27–37) variants were obtained through substitutions including AM S45W/Q50W and CGRP K35W/A36S designed to stabilize their β-turn. K46L and Y52F substitutions designed to exploit RAMP allosteric effects and direct peptide contacts, respectively, yielded AM variants with selectivity for the CGRP receptor over the AM1 receptor. AM(37–52) S45W/K46L/Q50W/Y52F exhibited nanomolar potency at the CGRP receptor and micromolar potency at AM1. A 2.8-A resolution crystal structure of this variant bound to the RAMP1-CLR ECD confirmed that it bound as designed. CGRP(27–37) N31D/S34P/K35W/A36S exhibited potency and selectivity comparable to the traditional antagonist CGRP(8–37). Giving this variant the ability to contact RAMP2 through the F37Y substitution increased affinity for AM1, but it still preferred the CGRP receptor. These potent peptide antagonists with altered selectivity inform the development of AM/CGRP-based pharmacological tools and support the hypothesis that RAMPs alter CLR ligand selectivity through allosteric effects and direct peptide contacts.
Siguiendo los rastros de los depósitos rituales: esbozo de un marco arqueológico para el estudio de las prácticas rituales en Palenque

Diversas excavaciones arqueologicas desarrolladas en las Tierras Bajas del sureste de Mexico, Guatemala y Belice han revelado patrones generalizados en las practica rituales, incluso en el tipo de materiales utilizados en ofrendas rituales y entierros humanos colocados dentro de los pisos y plazas de templos publicos y casas privadas. Sin embargo, las evidencias materiales de eventos rituales pasados parecen ser marcadamente diferentes en las Tierras Bajas noroccidentales, de modo particular en la ciudad de Palenque. Este articulo discute las ofrendas de los templos de Palenque, asi como los resultados preliminares de las excavaciones realizadas en un grupo residencial y encuentra que los materiales de los depositos rituales de este sitio a menudo comprenden posibles materiales organicos en lugar de aquellos encontrados tipicamente en los ejemplos de las Tierras Bajas orientales. Con el fin de considerar como tales practicas eran distintas en esta region, se propone un enfoque mas integral de una arqueologia del ritual que incluya la presencia de microrresiduos de las acciones rituales.
Electrophysiological Methods in the Study of Water Transport Across Cell Membranes

The study of water transport across the plasma membrane of animal cells has clearly lagged behind work on transport of ions and nutrients, although cell volume and hence water transport are essential for normal cell function. New physiological, biophysical and molecular approaches have been applied to the problem of water transport across cell membranes by several groups of investigators in recent years, resulting in significant progress in understanding the pathways and mechanisms of water transport and the nature and mechanisms of cell volume regulation. The purpose of this article is to review the use of electrophysiological approaches in the assessment of water transport across cell membranes.
Integration of Spatial Distribution in Imaging-Genetics

To better understand diseases such as cancer, it is crucial for computational inference to quantify the spatial distribution of various cell types within a tumor. To this end, we used Ripley’s K-statistic, which captures the spatial distribution patterns at different scales of both individual point sets and interactions between multiple point sets. We propose to improve the expressivity of histopathology image features by incorporating this descriptor to capture potential cellular interactions, especially interactions between lymphocytes and epithelial cells. We demonstrate the utility of the Ripley’s K-statistic by analyzing digital slides from 710 TCGA breast invasive carcinoma (BRCA) patients. In particular, we consider its use in the context of imaging-genetics to understand correlations between gene expression and image features using canonical correlation analysis (CCA). Our analysis shows that including these spatial features leads to more significant associations between image features and gene expression.
Monitoring of Pulse Pressure and Arterial Pressure Waveform Changes during the Valsalva Maneuver by a Portable Ultrasound System

This work presents non-invasive evaluation of the arterial blood pressure (ABP) waveform during the Valsalva maneuver. Ultrasound scanning is conducted to acquire blood flow and arterial distension signals. Motion-tolerant ultrasound measurement schemes are employed by using two wide rectangular transducers. Pulse pressure (PP) estimated at the common carotid artery is compared to that of a finger waveform measured by a volume clamping device. The changes of PP are correlated between the two measurements. A more depressed dicrotic notch during the Valsalva strain is observed, and beat-to-beat variations of PP and a pulse rate caused by respiration and baroreflex is observed during the control. This validation suggests novel opportunities to investigate the pathophysiology of cardiovascular diseases through the noninvasive ABP waveform monitoring during the stress test.
Diverse Alternative Learning Visions 2026–2066: Transforming and Reframing the University as a Lifelong Social Design Lab

California State University, East Bay (CSUEB) represents one of the most diverse campuses in the United States, and has started a number of programs in long term and futures thinking to celebrate diverse, alternative visions of the future. In the summer of 2016, for five weeks, multiple university stakeholders, including the University President, deans, faculty, staff and the university advancement team, engaged onsite in a futures design thinking process to envision a new Twenty first century commons space at the university. The ultimate goal was to transform and expand the university’s central library within the next ten years (by 2026) and for the next fifty years (to 2066). Six teams of stakeholders participated in forecasting, a human-centered design process shaping a twenty-first approach to education. In assessing this forecasting efforts, the following question was addressed: How did design futures thinking shape our vision of the new library and information commons space on the CSUEB campus? Although initial steps have been taken to realize the outcomes from this project, additional important work is needed to institutionalize full innovative changes.
Evaluation of the effects of an oral notch inhibitor, crenigacestat (LY3039478), on QT interval, and bioavailability studies conducted in healthy subjects

Crenigacestat (LY3039478) is a Notch inhibitor currently being investigated in advanced cancer patients. Conducting clinical pharmacology studies in healthy subjects avoids nonbeneficial drug exposures in cancer patients and mitigates confounding effects of disease state and concomitant medications. Three studies were conducted in healthy subjects, assessing safety, pharmacokinetics, effect on QT interval, and relative and absolute bioavailability of crenigacestat. Crenigacestat was administered as single 25, 50, or 75 mg oral doses or as an intravenous dose of 350 µg 13C15N2H-crenigacestat. Electrocardiogram measurements, and plasma and urine samples were collected up to 48 h postdose, and safety assessments were conducted up to 14 days postdose. Exposures were dose proportional in the 25 to 75 mg dose range and mean elimination half-life was approximately 5–6 h. The exposure achieved from the new formulated capsule was approximately 30% and 20% higher for area under the plasma concentration time curve from time zero to infinity [AUC(0–∞)] and maximum plasma concentration (Cmax), respectively, compared to the reference drug in capsule formulation. The geometric least-squares mean [90% confidence interval (CI)] absolute bioavailability of crenigacestat was 0.572 (0.532, 0.615). The regression slope (90% CI) of placebo-adjusted QTcF against crenigacestat plasma concentration was − 0.001 (− 0.006, 0.003), suggesting no significant linear association. Thirty-nine subjects completed the studies and the majority of adverse events were mild. Single oral doses of 25 to 75 mg crenigacestat and an IV dose of 350 µg 13C15N2H-crenigacestat were well tolerated in healthy subjects.
Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort

Background and aims Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn's disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis. Methods This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30. Results Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7-2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors. Conclusions Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.
Neurodevelopmental Outcomes in Children with Complex Congenital Heart Disease

The purpose of this article is to better understand the challenges that children with congenital heart disease (CHD) face and the elements that put them at higher risk, and also to review existing interventions and discuss how they impact long-term neurodevelopment. Approximately 1–2% of all children are born each year with CHD, and survival into adulthood now surpasses 80%. It has thus become increasingly more important to recognize and manage the common complications seen in this population. There are a number of factors that contribute to increased risk for adverse neurodevelopmental outcomes, including underlying genetic abnormalities, altered cerebral blood flow, pre- and post-operative factors, sub-optimal nutrition, parental stress, and socioeconomic considerations. These are important to recognize and address where possible. It is now also apparent that there is a unique pattern of neurodevelopmental delays seen in this population and they encompass motor, language, cognitive, executive function, adaptive, behavioral, and autism spectrum disorder parameters. CHD affects many individuals and the neurodevelopmental impact is not insignificant. Early identification and management through cardiac neurodevelopmental programs and support through programs such as early intervention are critical to optimizing the neurodevelopmental outcomes and quality of life of individuals with CHD. Future directions should include further research into what impacts neurodevelopmental outcomes in children with CHD and how to intervene.
Are You Speaking: Real-Time Speech Activity Detection via Landmark Pooling Network

In this paper, we propose a novel visual information based framework to solve the real-time speech activity detection problem. Unlike conventional methods which commonly use the audio signal as input, our approach incorporates facial information into a deep neural network for feature learning. Instead of using the whole input image, we further develop a novel end-to-end landmark pooling network to act as an attention-guide scheme to help the deep neural network only focus the related portion of the input image. This helps the network to precisely and efficiently learn highly discriminative features for speech activities. What’s more, we implement a recurrent neural network with the gated recurrent unit scheme to make use of the sequential information from video to produce the final decision. To give a comprehensive evaluation of the proposed method, we collect a large-scale dataset from unconstrained speech activities, which consists of a large number of speech/non-speech video sequences under various kinds of degradation. Experimental results demonstrate the superiority of our proposed pipeline over previous approach in terms of performance and efficiency.
Resonant Two-Photon Photoelectron Imaging and Intersystem Crossing from Excited Dipole-Bound States of Cold Anions

We report the observation of a dipole-bound state (DBS) 659 cm-1 below the electron detachment threshold of cryogenically cooled deprotonated 4,4'-biphenol anion (bPh-) and 19 of its lowest vibrational levels. Resonant two-photon photoelectron imaging (R2P-PEI) via the vibrational levels of the DBS displays a sharp peak with a constant binding energy. This observation indicates vertical detachment from the vibrational levels of the DBS to the corresponding neutral levels with the conservation of the vibrational energy, suggesting that the highly diffuse electron in the DBS has little effect on the neutral core. The R2P-PEI spectra also exhibit two features at lower binding energies, which come from intersystem crossings from the DBS to two lower-lying valence-bound triplet excited states of bPh-. The current study discloses the first R2P-PEI spectra from vibrational excited states of a DBS and direct spectroscopic evidence of transitions from a DBS to valence-bound states of anions.
Functions of the Rule of Law

This concise essay examines multiple manifest and latent functions of the rule of law. The rule of law is characterized as a society in which government officials and the populace are generally bound by and abide law. The functions covered include: personal and collective security and trust; integration of society; legal restrictions on officials; liberty and guiding conduct; economic development; a pivotal place for legal professionals; entrenching power structures; normative commitment and critical standard; and rhetoric. The discussion raises core issues about each function.
Accurate estimation of microbial sequence diversity with Distanced.

Motivation Microbes are the most diverse organisms on the planet. Deep sequencing of ribosomal DNA (rDNA) suggests thousands of different microbes may be present in a single sample. However, errors in sequencing have made any estimate of within-sample (alpha) diversity uncertain. Results We developed a tool to estimate alpha diversity of rDNA sequences from microbes (and other sequences). Our tool, Distanced, calculates how different (distant) sequences would be without sequencing errors. It does this using a Bayesian approach. Using this approach, Distanced accurately estimated alpha diversity of rDNA sequences from bacteria and fungi. It had lower root mean square prediction error (RMSPE) than when using no tool (leaving sequencing errors uncorrected). It was also accurate with non-microbial sequences (antibody mRNA). State-of-the-art tools (DADA2 and Deblur) were far less accurate. They often had higher RMSPE than when using no tool. Distanced thus represents an improvement over existing tools. Distanced will be useful to several disciplines, given microbial diversity affects everything from human health to ecosystem function. Availability and implementation Distanced is freely available at https://github.com/thackmann/Distanced. Supplementary information Supplementary data are available at Bioinformatics online.
First Year “Must Do’s”: Prepared for Building a Clinical Practice

The leap from graduating chief resident or fellow to attending physician is one of the most critical and daunting times in a surgeon’s career. Here, we have outlined key “must dos” in the first year to ensure that milestones are reached and the research mission and personal/family life does not suffer during the course of building an academic clinical practice. This includes identifying requirements for board certification early and planning backwards from these dates; developing a strategic debt management plan, retirement and insurance plan; keeping a case log and identifying clinical mentors. The basics of laboratory set up including how to leverage mentors’ experience when hiring laboratory staff, negotiating research regulations, and curating a reputation are emphasized.
A Macrocyclic Ruthenium Carbene for Size-Selective Alkene Metathesis

The synthesis of a macrocyclic Ru carbene catalyst for selective cross alkene metathesis is reported. The new catalyst showed different reactivity for various type 1 alkenes in homodimerization which correlated with the aggregrate size of the allylic substituent. The altered reactivity profile allowed for selective product formation in competition cross alkene metathesis between two different type 1 alkenes and tert-butyl acrylate. Selectivity in these reactions is attributed to the ability of the macrocyclic catalyst to differentiate alkenes based on their size. Two preparative examples of cross metathesis with the macrocyclic catalyst are also provided.
Autoimmunity and organ damage in systemic lupus erythematosus

Impressive progress has been made over the last several years toward understanding how almost every aspect of the immune system contributes to the expression of systemic autoimmunity. In parallel, studies have shed light on the mechanisms that contribute to organ inflammation and damage. New approaches that address the complicated interaction between genetic variants, epigenetic processes, sex and the environment promise to enlighten the multitude of pathways that lead to what is clinically defined as systemic lupus erythematosus. It is expected that each patient owns a unique 'interactome', which will dictate specific treatment.
Passive Investment and Share Repurchases

We investigate the association between passive investment and share repurchases, both at historically high levels and the subject of scrutiny. We report that firms with more passive ownership exhibit higher levels of repurchase activity, including repurchases resulting in reported earnings that meets or beats analysts’ earnings forecasts. We also find that repurchase activity more negatively affects firms’ future employment, capital expenditures, and performance when the firm has more passive owners. We conclude that passive investment is associated with an increase in the quantity and a reduction in the quality of firms’ repurchase activities.
Ionizing Radiation and Life

Ionizing radiation includes all electromagnetic waves from ultraviolet light to gamma rays, for the simple reason that the localized interaction of light with matter is by photons with energy proportional to frequency. With frequencies below ultraviolet light in the spectrum, the photons have insufficient energy to break typical organic molecular bonds. Subatomic particles moving with high kinetic energy can also be ionizing, and therefore potentially damaging to organic tissue. These realizations make radiation dosimetry an important topic. On the positive side, mild radiation facilitates genetic mutation, necessary for evolution, and strong radiation can be used in therapy to purposely kill aberrant cells.
Reorganisation and development of a consultant-led cardiology service leads to substantial reductions in length of stay, all-cause inhospital and 30-day post-discharge mortality in acute coronary syndromes

Background East Lancashire Hospitals NHS Trust (ELHT) reorganised its services in October 2007 with all acute admissions sent to one site (Royal Blackburn Hospital). This allowed the development of a 24/7 consultant-led cardiology service (three newly appointed interventional and three non-interventional cardiologists). Management of a new 10-bedded coronary care unit was taken over by the cardiologists who also provided a daily ward round in the medical admissions unit and the general cardiology ward. The emphasis was on the early recognition of the high to intermediate risk patients who were most likely to benefit from assessment and management directed by consultant cardiologists. Methods We performed an audit of all patients admitted with acute coronary syndromes (ACS) between two periods: group 1—between October 2006 and September 2007 and group 2—between October 2007 and September 2008. The data were obtained from the MINAP database. We looked at the following endpoints: length of stay, inhospital and 30-day postdischarge all-cause mortality. Results 633 patients were admitted between 2006 and 2007 and 748 patients between 2007 and 2008. The mean age was higher (70.3 vs 68.2 years; p = 0.006) and there was a greater proportion of women (42% vs 35%; p = 0.008) in group 1. There was no difference between the two groups in terms of the number of patients with diabetes or hypertension at admission. There was a significant reduction in the length of stay from a median (interquartile range) of 7 days (5–11) to 5 days (3–9); p Conclusion The development of a modern and comprehensive consultant cardiologist-led service directed towards the early recognition and appropriate management of patients admitted with ACS is associated with impressive reductions in all-cause mortality. This improvement in outcomes occurred with an equally impressive reduction in hospital length of stay.
Inclusion of a music learner with ASD through play-full intersubjectivity:

Through a case study of Jad (pseudonym), a music learner with autism spectrum disorder (ASD), I sought to understand his experiences as he engaged in peer scaffolding activities of a choral ensembl...
Termination of Related and Unrelated Joint Ventures: A Contingency Approach

Abstract Previous research has investigated various factors that influence joint venture (JV) termination. Yet the majority of studies do not distinguish between different types of JVs, particularly whether a JV is related or unrelated to the parent firm. Due to their inherent differences, related and unrelated JVs are likely to evolve distinctly, and their tendency to terminate may also differ under various conditions. This study takes a contingency approach and argues the impact of various factors on JV termination depends upon JV relatedness. An event history analysis finds increases in environmental uncertainty and higher resource complementarity reduce the likelihood that a firm will terminate unrelated JVs as compared to related JVs. Conversely parent firm performance and wider JV scope increase the likelihood that the firm will terminate unrelated JVs as compared to related JVs. The findings suggest the need to consider JV relatedness in understanding JV evolution and termination.
Retrogression and Reaging of AA7075 and AA6013 Aluminum Alloys

Retrogression and reaging (RRA) is of interest to the automotive industry for manufacturing components of high-strength aluminum alloys. RRA heat treatments are investigated for AA7075-T6 and AA6013-T6 materials. Retrogression is demonstrated to be a thermally activated process reasonably characterized with a single activation energy. Activation energies for retrogression are measured as 97 ± 7 and 160 ± 30 kJ/mol for AA7075-T6 and AA6013-T6, respectively. Critical retrogression times, tR* and t R max , are defined and measured across a range of retrogression temperatures. These data are used with the concept of reduced time to predict combinations of temperature and time that produce successful retrogression heat treatments. Recommended retrogression heat treatments are 200 °C for 3 to 12 minutes for AA7075-T6 and 240 °C for 7 minutes for AA6013-T6. Data from reaging heat treatments confirm a significant RRA response in AA6013. Recommended reaging heat treatments are 120 °C for 24 hours for retrogressed AA7075 and 190 °C for 1 hour for retrogressed AA6013. A reaging heat treatment that simulates the automotive paint-bake cycle, 185 °C for 25 minutes, is almost as effective as the recommended reaging heat treatment for AA6013 but is significantly less effective than the recommended reaging heat treatment for AA7075.
Comparison of the Limb-lead Electrocardiogram to the 12-Lead Electrocardiogram for Identifying Conditions Associated with Sudden Cardiac Death in Youth Athletes

The optimal screening strategy to prevent sudden cardiac death (SCD) in athletes remains unknown. Pre-participation screening with electrocardiogram (ECG) remains controversial. The utility and accuracy of limb-lead (LL) ECG alone in identifying cardiac abnormalities associated with SCD has not been studied. This study was a comparative secondary data analysis, comparing the interpretation accuracy of 4 physicians evaluating publicly available ECGs of the most common cardiac conditions associated with SCD in athletes. Each physician interpreted a total of 100 ECGs: 50 normal ECGs (25 LL and 25 standard 12L) and 50 abnormal ECGs (25 LL and 25 standard 12L). The agreement between LL ECGs and 12L ECGs was assessed by Cohen's kappa coefficient and the accuracy of identifying an abnormal ECG was compared across LL and 12L ECGs using a chi-squared test. Inter-rater reliability was assessed by estimating the Fleiss's kappa coefficient. The sensitivity of LL ECG and 12L ECG was identical at 86%. The specificity of LL ECG was 75% (95% CI = 65% to 83%) and 12L ECG was 82% (95% CI = 73% to 89%). Substantial agreement was seen between LL ECG and 12L ECG interpretation across all readers (k = 0.63; 95% CI = 0.49 to 0.77). Interpretation accuracy was 81% (95% CI = 74% to 86%) and 84% (95% CI 78% to 89%) using LL ECG and 12L ECG, respectively (p = 0.43). In conclusion, the accuracy, sensitivity, and specificity were high and comparable for both LL ECG and 12L ECG in identifying cardiovascular conditions associated with SCD. Agreement between LL ECG and 12L ECG was substantial.
The Challenge of the Rule of Law

THE lecture last week considered the Rule of Law concept in historical perspective. Aside from its possible, highly restricted connotation of public order maintained by the force of politically organized society, three basic meanings or emphases were identified in discussions of the Rule of Law: first, certain constitutional principles, particularly those ascribed by Dicey to 19th-century Britain; second, certain valuable procedural safeguards of a fair trial; and third, those asserted universal and perhaps immutable principles, derived from God or Nature by the rational faculties of man, available to guide and, in some views, to invalidate positive legal action. Without denying the significance of any of these emphases, I suggested certain criticisms as relevant insofar as any one emphasis is advanced as the sole definition of the Rule of Law, and that concept, in turn, is offered as a general safeguard against abuses of the power of the modern state. Today the analysis of the Rule of Law will be continued, but from a somewhat different perspective. I hope to come somewhat closer to the heart of the problem which underlies thought and discussion about the Rule of Law and then, proceeding functionally, synthesize a concept somewhat more responsive to the needs of that basic problem. Initially, it seems essential to consider what is meant by law, if the "Rule thereof" is to mean anything. This necessity is regrettable, for the literature overflows with much good ink spilled over this question. The discussion of the meaning of "law" has often been acrimonious and frequently arid. Why then must it be prolonged? Cannot this definitional problem be set aside so that we can get on with our chores? In Shakespeare's Verona, Juliet inquires of Romeo, "What's in a name? That which we call a rose By any other name would smell as sweet." The obvious good sense which underlies the question and comment is very appealing. Why not conclude that definition may properly be stipulative, and if anyone questions
Ranking structure in communication fabrics

We present our experience and case studies for proving liveness of communication fabrics. A methodology is developed that reveals ranking structure underlying the state spaces of such fabrics. This enables an efficient proof of liveness using the k-LIVENESS algorithm leveraging this ranking structure. An open-source infrastructure for the k-LIVENESS algorithm has been implemented that has a provision for specifying and leveraging ranking structures in the form of stabilizing constraints. A significant speed-up was achieved with this modified k-LIVENESS framework when proving response property of communication fabrics.
Characterization of the glutamyl-tRNA(Gln)-to-glutaminyl-tRNA(Gln) amidotransferase reaction of Bacillus subtilis.

In Bacillus subtilis, the formation of glutaminyl-tRNA is accomplished by first charging tRNA(Gln) with glutamate, which is then amidated. Glutamine was preferred over asparagine and ammonia as the amide donor in vitro. There is a functional analogy of this reaction to that catalyzed by glutamine synthetase. Homogeneous glutamine synthetase, from either B. subtilis or Escherichia coli, catalyzed the amidotransferase reaction but only about 3 to 5% as well as a partially purified preparation from B. subtilis. Several classes of glutamine synthetase mutants of B. subtilis, however, were unaltered in the amidotransferase reaction. In addition, there was no inhibition by inhibitors of either glutamine synthetase or other amidotransferases. A unique, rather labile activity seems to be required for this reaction. Images
Optimizing flow control for buffered switches

We address a problem often neglected in the presentation of credit flow control (FC) schemes for buffered switches, namely the issue of FC bandwidth and FC optimization, i.e. how many and which credits to return per packet cycle. Under the assumption of bursty traffic with uniform destinations, we show via simulations that, independent of switch size and without loss in performance, the number of credits to be returned can be reduced to one. We further introduce the notion of credit contention and credit scheduling. We analyze four credit scheduling strategies under varying system and buffer size. Our results demonstrate that, with a proper credit scheduler in place, contention resolution is resolved much faster than with conventional schemes. Our findings suggest that scheduling of credits is a means for the switch to determine its future arrivals during contention phases.
Philosophical and Ethical Foundations of Systems Thinking

Drawing on more than a decade of research on the social implications of systems thinking, as well as practical experience in integrative, community-based approaches to education, this paper is an inquiry into philosophical and ethical considerations growing out of recent developments in systems thinking. In his foundational work on general system theory, Ludwig von Bertalanffy distinguishes between three general developments in the systems field: systems technology, systems science, and systems philosophy. These three dimensions of systems thinking each nurture distinct and often widely divergent theoretical and practical orientations. In his abstract for this session, Gary Metcalf asks whether the systems approach really has anything to offer. Science is a form of social feedback; it has created an enormous body of knowledge about the world and shaped humanity’s understanding of the nature of our collective reality. Knowledge then informs action. Assumptions built into scientific frameworks condition certain kinds of actions, as Bertalanffy has noted. Systems thinking as science nurtures a way of thinking that engenders a different kind of practice; systems as philosophy cultivates an ethic of integration and collaboration that has the potential to transform the nature of social organization. Although humanity still has a lot to learn about living more harmoniously and sustainably, systems thinking has made significant contributions in this direction in many fields, both theoretical and practical. The challenge is to integrate what we have learned, to communicate these insights to a larger audience, and to nurture institutional practices that honor the ethical principles inherent in the systems view.
4-Aminobutyrate Aminotransferase

The analogues 5-phospho-pyridoxal-aminooxyacetate and 4-vinyl-pyridoxal 5-phosphate inhibit reduced 4-aminobutyrate aminotransferase reconstituted with pyridoxal 5-phosphate, but they do not affect the catalytic activity of the holoenzyme. The binding of the 5-phosphopyridoxal adducts to the holoenzyme was monitored by measuring the fluorescence properties of the protein and the ligands. The presence of nonequivalent binding sites in reduced samples of enzyme containing 1 mol and 1.8 mol P-pyridoxyl residues/mol dimer was detected by steady and nanosecond fluorescence spectroscopy. The spectroscopic properties (fluorescence lifetime τ= 1 ns, polarization = 0.36 and quantum yield = 0.01) of the first molecule of 5-phospho-pyridoxyl are different from the properties of the second molecule of 5-phospho-pyridoxyl covalently bound to the enzyme (τ= 2.1 ns, P= 0.16, QT= 0.1). The spectroscopic properties of pyridoxal 5-phosphate and 5-phospho-pyridoxal-aminooxyacetate bound to different sites on the holoenzyme can be used to deduce proximity relationships between the catalytic sites of 4-aminobutyrate aminotransferase. On the basis of resonance energy transfer measurements, it is proposed that a distance of 27 A (2.7 nm) separates the two catalytic binding sites.
Performance of Reed-Solomon coded beamforming in MIMO Rayleigh fading channels

In this paper, we study Reed-Solomon (RS) coded beamforming in multiple-input-multiple-output (MIMO) Rayleigh fading channels. To combat the fading, we introduce a block interleaver into RS-coded beamforming systems and we present the performance analysis of such systems. We show that the interleaver can greatly improve the performance of RS coded beamforming systems, especially in the systems with a small number of antennas. We also observe that the interleaver gain in a RS coded beamforming system vanishes as the number of antennas increases. We illustrate that the proposed approach has potential to evaluate the tradeoffs between spatial diversity and time diversity via symbol interleaving.
Origin and evolution of polygonal cracks in hydrous sulphate sands, White Sands National Monument, New Mexico

The nucleation and propagation of polygonal cracks in hydrous sulphate dunes at White Sands National Monument, New Mexico, are affected by water availability, transport through the sand and exchange with the atmosphere. These gypsum sands are cohesive enough to crack due to capillary forces and gypsum cements formed during evaporation. Surface cracks form five-sided polygons with a variety of triple-junction angles. Cracks extend down to variable depths and polygons increase in size with depth, showing a maturation similar to experimentally produced polygonal columns in drying corn starch. Results from two years of monitoring crack geometries, temperature and humidity demonstrate that cracks form when water is lost to the atmosphere through the transport of water vapour. Subsurface relative humidity below 5 to 10 cm is almost always maintained at 100% by the evaporation and condensation of water in thin films on grains. The amplitude of daily temperature and thus absolute humidity changes decreases with depth, consistent with lower evaporation and condensation rates with increasing depth. Changes in absolute humidity and the contrast between humidity in pore spaces versus the overlying atmosphere result in significant water loss from the dunes except during times of precipitation and frost/dew condensation. This water loss allows cracks to nucleate and propagate into the dunes. This study hypothesizes that crack tips propagate into sand to the depth at which thin films of water on grains are drying, and that this depth varies from the surface of the dune during precipitation events to depths greater than 45 cm when dunes are drier.
Micronutrient status of the rice plant

Soil solution Zn, Cu, Mn and Fe concentrations which were monitored throughout the growing season were found to be representative for flooded rice culture. Plant Zn, Cu, Mn and Fe contents of top, middle and bottom leaves as well as whole plants were also measured periodically throughout the growing season. These data were found to be within reported ranges for rice plants grown on flooded soils. Simple regression analyses were performed between plant micronutrient contents for each plant part sampled and the corresponding soil solution values. Results showed that the most promising portions of the rice plant to sample for accurate assessment of plant response to changes in soil solution micronutrient concentration as a function of time are as follows: (a) for Zn, bottom leaf; (b) for Cu, top or bottom leaf, whole plant; (c) for Mn, top leaf and (d) for Fe, bottom leaf or whole plant. re]19750915
Gender encounters in a virtual community: identity formation and acceptance

ABSTRACT Identity formation and acceptance in a virtual community are areas that one could consider the stepping stones to understanding the myriad nuances that compose a social relationship in cyberspace. This paper explores a Multi-User Domain (MUD) called “Multiple Worlds” (MW), a “community talker” dealing with adult conversations on sexually explicit topics. It gives an account of how people strike up conversations under their new identities. It also discusses the role gender plays in identity formation and its subsequent acceptance by other members in that community. Finally, the paper presents some issues for the future study of cybercultures.
Acoustic liquid manipulation

Acoustic Liquid Manipulation (ALM) is a term coined to describe the use of non-linear acoustics to move liquid, manipulate liquid surfaces, and propel buoyant objects. It differs from acoustic levitation because it does not rely on standing waves but instead uses focused directed beams operating at RF frequencies, employs burst modulation and transmits through liquids. Transducers with simple focusing lenses were employed initially but now the emphasis is on acoustic phased arrays. Applications both real and contemplated involve the acoustic dispensing of droplets from needles, ejection of droplets from free surface pools, and acoustic manipulation of free surfaces, bubbles and objects. NASA is evaluating these techniques for a variety of multiphase fluid systems including space experiments and systems for the Space Station. Meanwhile, ground manufacturing applications range from PC board electronics to micro-electronic and micro-machine scale devices. ALM is already being developed to reduce or eliminate masks in plating and etching operations, which, in turn, reduces waste products.
Effect of Massive Progestational Hormone Treatment on the Parturient Human Uterus

Clinical trials were designed to examine the question of whether progestational hormone treatment distinctly and predictably affects the already evolved spontaneous activity of the parturient human uterus. The specific question was whether a single massive dose of a potent progestational hormone predictably suppresses the activity of the parturient human uterus. 62 patients were in the completed study 38 controls and 24 hormone-treated patients. Only those patients were placed in the study group who displayed advanced spontaneous activity during early labor. After spontaneous activity had been recorded for 1 hour the patients received intramuscularly a single massive dose of a potent progestational hormone medroxyprogesterone acetate (MPA). The intraamniotic pressure was continuously measured after the administration of the hormone until the time of delivery. The difference at 5 and 10 hours after hormone treatment was statistically significant. The control curve had a slight upward tendency; the experimental curve a slight downward tendency. In that these curves represent averages the position of any single point along the curve is determined by the position of the majorty of points at this particular time. Thus the eventual acceleration of activity at the end of labor of the MPA-treated individual patients was masked by the low average activity of those women in whom acceleration had not yet occurred. Considering averages it appears that massive MPA treatment induced a slight and transient damping effect on uterine activity during early labor.
A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients.

Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for > or = 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ . kg body wt-1 . d-1, 1.5 g protein . kg body wt-1 . d-1, and 0.3 g glutamine . kg body wt-1 . d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 mumol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses.
Fuzzy linguistic model based control

A new approach to rejecting measurable disturbances in multistage continuous manufacturing processes is presented. This approach, called fuzzy linguistic model-based compensation, is empirically shown to be effective, in comparison with ordinary feedback, in predicting the influence of the disturbance and countering its effect. It is shown how this strategy can improve the behavior of the system in the presence of significant time delay which is common in continuous manufacturing processes. How this approach can be applied to structurally similar situations and possibly extended into analytic form is considered. >