cssi/SciSciGPT-SciSciNet huggingface dataset:
G protein effects on Ca2+ release and excitation-contraction coupling in skeletal muscle fibers

Skeletal muscle excitation-contraction (EC) coupling may involve secondary mechanisms, such as those involving G proteins. The aim of this study was to identify possible G protein effects on sarcoplasmic reticulum (SR) Ca2+ release, in general, and on voltage-dependent EC coupling, in particular. Effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) were studied using a single peeled rabbit skeletal muscle fiber preparation that is capable of releasing SR Ca2+ in response to transverse tubule (TT) depolarization. Because of possible nonspecific and residual effects of 200 microM GTP gamma S, a lower concentration of 50 microM GTP gamma S was used to stimulate G proteins in the peeled fiber system. Under conditions for steady-state (resting) polarization of TT, GTP gamma S rarely elicited SR Ca2+ release. When the TTs are in steady-state (resting) depolarization, 50 microM GTP gamma S or GTP elicited SR Ca2+ release and associated tension transients in only 69% of fibers tested. In contrast GTP gamma S always augmented Ca2+ release during TT depolarization-induced EC coupling. These results indicate the presence of at least two excitatory G proteins for SR Ca2+ release, only one of which is a modulator, albeit nonessential, of peeled fiber EC coupling.
Correlation of left phrenic arterial flow with regional diaphragmatic blood flow.

Previous work has assumed that left phrenic arterial blood flow (Qpa) reflects diaphragmatic blood flow. We have tested this assumption in four anesthetized mechanically ventilated dogs by measuring Qpa with a Doppler flow probe and regional diaphragmatic blood flow with radiolabeled microspheres. Flows were examined during control 1 (diaphragm at rest), pacing (phrenic pacing: rate 20/min, duty cycle 0.33), control 2, hypotension (rest with mean arterial pressure reduced by 45% of the control 1 value), and hypotension and pacing. As a percent of the control 1 value, Qpa was 511 +/- 107% during pacing, 139 +/- 12% during control 2, 40 +/- 13% during hypotension, and finally 347 +/- 31% during hypotension and pacing. Similarly, percent left hemidiaphragmatic blood flow (Qlh) was 362 +/- 91% during pacing, 91 +/- 10% during control 2, 14 +/- 2% during hypotension, and finally 213 +/- 50% during hypotension and pacing. The changes in flow to the left costal and crural diaphragm were similar to those recorded for Qlh. We conclude that Qpa correlates with total and regional diaphragmatic blood flow (r = 0.77–0.81, P less than 0.001) under conditions of supramaximal phrenic nerve stimulation in which the metabolic demands of the region perfused by the phrenic artery are presumed to be similar to the metabolic demands of the rest of the diaphragm.
Correction for Chatterjee et al., RsmC of Erwinia carotovora subsp. carotovora Negatively Controls Motility, Extracellular Protein Production, and Virulence by Binding FlhD and Modulating Transcriptional Activity of the Master Regulator, FlhDC

Volume 191, no. 14, p. [4582–4593][1], 2009. Pages 4585 and 4586, Fig. 2 and 3: We recently discovered image duplications in two figures in this article. Well images for protease (Prt) activity in [Fig. 2A][2] (FlhDC+ RsmC−) and C (AC5142/ flhDC + ) and 3A (RsmC+) appear to be duplicates.
Biochemical Properties of Three Extracellular Pectate Lyases of ErwiniaChrysanthemi EC16

Pectate lyase (PEL) is the major factor in the development of soft rot diseases caused by E. chrysanthemi. The strain EC16 produces several pectate lyases, of which the structural genes for some have been cloned. To compare the biochemical and immunological properties and to identify the respective structural genes, three pectate lyases (PEL-A, PEL-B, and PEL-C) were purified by ultrafiltration of culture supernatant, chromatography on pectate gels, and chromatofocusing. The apparent molecular weights (and pIs) of PEL-A, PEL-B, and PEL-C were 43 Kd (7.8), 45 Kd (8.2) and 50 Kd (9.9), respectively. The pectate lyases had similar calcium requirements, pH optima, affinities for polygalacturonate (PGT), and rates of substrate cleavage. The enzymes, however, differed in their mode of PGT cleavage in that PEL-C produced unsaturated dimer and oligomers (trimer, tetramer). In addition, the rate at which the enzymes caused electrolyte loss from potato tuber tissue differed with PEL-C being the most efficient, followed by PEL-B and PEL-A. The structural gene of PEL-A was identified by comparing the periplasmic proteins of a PEL+E. coli with the purified enzyme in SDS-polyacrylamide gels, while the PEL-C structural gene was identified by antigen titration. The gene specifying PEL-B remains to be identified.
Optimal Shortest Path and Minimum-Link Path Queries in the Presence of Obstacles (Extended Abstract)

We present efficient algorithms for shortest-path and minimumlink-path queries between two convex polygons inside a simple polygon, which acts as an obstacle to be avoided. We also extend our results to the dynamic case, and give a unified data structure that supports both queries for convex polygons in the same region of a connected planar subdivision. Performing shortest-path queries is a variation of the wellstudied separation problem, which has not been efficiently solved before in the presence of obstacles. Also, it was not previously known how to perform minimum-link-path queries in a dynamic environment, even for two-point queries.
Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a life-threatening Mendelian disorder with a mean life expectancy of 33 years despite maximally tolerated standard lipid-lowering therapies. This disease is an ideal candidate for gene therapy, and in the last few years, a number of exciting developments have brought this approach closer to the clinic than ever before. In this review, we discuss in detail the most advanced of these developments, a recombinant adeno-associated virus (AAV) vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing. We also review ongoing development of approaches to enhance transgene expression, improve the efficiency of hepatocyte transduction, and minimize the AAV capsid-specific adaptive immune response. We include a summary of key gene therapy approaches for HoFH in pre-clinical development, including RNA silencing of t﻿he gene encoding HMG-CoA reductase (HMGCR) and induced pluripotent stem cell transplant therapy.
Seismic Performance of Light-Framed Wood Structures with Toggle-Braced Fluid Dampers

In recent years, seismic damping systems have been employed in numerous steel and concrete framed buildings. Such systems dissipate a significant portion of the seismic input energy, thereby relieving the energy dissipation demand on the structural framing system and thus reducing damage. As part of a NEESR project to develop a performance-based approach to seismic design of multi-story light-framed wood structures, the application of damping systems to such structures has been evaluated via seismic shaking table tests and numerical simulations. This paper focuses on the results from shaking table tests of wood shear walls employing toggle-braced fluid dampers. Within the context of performance-based seismic design, the effect of the fluid dampers on the deformation demand and hysteretic energy dissipation demand is emphasized. The results demonstrate that toggle-braced fluid dampers provide a significant increase in the seismic resistance of the walls, allowing them to achieve high levels of performance when subjected to strong ground motions.
Observations On The Biting Of Humans By Euhoplopsyllus Glacialis Affinis (Siphonaptera: Pulicidae) And A Review Of Its Plague-Transmission Potential

Three separate instances are reported in which Euhoplopsyllus glacialis affinis , a flea parasitizing cottontails ( Sylvilagus spp.), was found invading buildings and biting humans. In one instance the plague organism, Yersinia pestis , was isolated from fleas collected by those bitten. A review of published information and epidemiological records and data presented in this study indicate that E. g. affinis is of minimal importance as a plague vector, and that there is little risk of human infection from this flea.
Impacts of Tapered Sidewall Profiles With High Aspect Ratio on Subwavelength Grating Structure

We have numerically demonstrated the significant impacts on the resonance mode characteristics of subwavelength grating structures due to tapered sidewall profile and high aspect ratio, which is normally obtained due to the practical CMOS-compatible fabrication and etching processes. Our simulation results have revealed that the tapered sidewall profile with high aspect ratio plays important roles on the resonance mode behavior of subwavelength grating photonic devices. The coupling mechanism between the guided mode resonance and the grating cavity is also emphasized. Our numerical studies can be utilized for a series of integrated photonic devices applications, such as compact optical filter, photonic amplifier, and lasers, while considering realistic subwavelength grating structures due to current nanoelectronics fabrication process.
Essential HIV/AIDS facts: What you need to know in 1992

The fast pace of HIV/AIDS research and the wide spectrum of issues involved can be intimidating for busy primary care physicians who see HIV-infected patients infrequently. The information covered in this article is intended to form a core that should be a part of all physicians' medical knowledge today.
Resultats Recents Lies Au Theoreme D’Irreductibilite de Hilbert

Le theoreme d’irreuctibilite de Hilbert est un reltat de la fin du siele dernier [17]. Le probleme est le suivant: etant donnes un corps k et Pl ,…, Pn n polynomes irreductibles dans k(X1,..., Xr)[Y1 ,..., Ys] , montrer que l’ensemble qu’on note classiquement Hk(P1 ,..., Pn), constitue des specialisations (xl , x2 ,..., xr) des indeterminees (X1 ,..., Xr) pour lesquelles les polynomes Pi(xl ,..., xr , Y1 ,..., Ys), i= 1,2 ,..., n, sont irreductibles dans k[Y1 ,..., Ys], contient beaucoup d’elements de kr. Precisement, on appelle partie hilbertienne de kr tout ensemble, intersection d’un ensemble du type Hk(P1 ,..., Pn) avec un ouvert de Zariski de kr et on dit que le corps k est hilbertien si pour tout entier r≥1, les parties hilbertiennes sont non vides. On appelle aussi ensemble mince tout ensemble dont le complementaire contient une partie hilbertienne. En ces termes, le theoreme d’irreductibilite de Hilbert s’enonce:
Abstract A49: Quality of life in lower income, primarily African American, cancer survivors

Introduction: While racial/ethnic cancer health disparities in incidence, treatment, and mortality are well documented, the psychosocial characteristics of underserved, minority cancer survivors are poorly understood. In this study, we explore quality of life in lower income, primarily African American survivors in treatment or follow-up for a first cancer diagnosis. Methods: We examined baseline data from an intervention trial conducted in a safety net hospital in Alabama. Health related quality of life (QOL) was measured by three subscales of the Functional Assessment of Cancer Therapy-General Scale (FACT-G): social/family well being (SWB, scale range 0 – 28), functional well-being (FWB, scale range 0 – 28) and emotional well-being (EWB, scale range 0 – 24). QOL subscales for the total sample were examined by using t-score conversions to obtain a normative comparison to a reference group of 2236 adult cancer patients (mean of 50 and range of 0 – 100; Bruckner et al., 2005). Regression analyses were conducted to examine the relation between QOL subscales and potential correlates including age, marital status, education, cancer type and time since diagnosis. Results: At the time of this analysis, a total of 106 participants were enrolled in the study. Of these, 72 (67.9%) were female and 82 (77.4%) were African American. The mean age was 53 years (±10) and 81 (76.4%) had up to 12 years of education. The average annual income was less than $10,000. The most common cancer diagnoses were breast (36.8%) and colorectal (15.1%) cancer. The mean time since diagnosis was 28.5 months. On the FACT subscales, participants reported a mean of: 22.0 ±5.8 on SWB; 17.1 ±7.3 on FWB; and 19.1 ±4.8 on EWB, with higher scores suggesting greater well-being. Converting the FACT-G subscales to t-scores yielded respective SWB, FWB and EWB scores of 49.8, 47.2 and 50.1. Of potential correlates entered into the regression models for SWB, EWB and FWB, only older age was significantly associated with better FWB (p = .05) and longer time since diagnosis was significantly associated with better SWB (p = .05). Conclusions: Quality of life subscales SWB, FWB and EWB for these lower income, predominantly African American cancer survivors compare well to the more heterogeneous reference group of adult cancer patients, especially for older survivors and those further away from diagnosis. These findings suggest the need for further research to identify the characteristics contributing to QOL success. It also suggests further research into the use of the FACT-G in this population as it may not adequately measure the quality of life domains of poor cancer survivors.
Quantifying uncertainty in outdoor air flow control and its impacts on building performance simulation and fault detection

Abstract There is usually discrepancy between deterministic modeling and actual operations of HVAC (heating, ventilation and air-conditioning) systems to some extent depending on the model comprehensiveness. Our main challenge is to express associated uncertainty in model outcomes in a way that is helpful to those trying to use the predictions from simulations to make decisions. Considerable research is underway to quantify uncertainty in building simulation. A recent trend is to include HVAC system parameters in uncertainty analysis. Outdoor air control has significant impact on energy consumption and indoor air quality. This study investigates the uncertainties of outdoor air control of a particular system type. Based on the analysis, the authors have identified the uncertain parameters, quantified their uncertainty patterns and mapped them to building performance simulation in terms of energy consumption and ventilation requirement. The simulated results show that the uncertainty in outdoor air control can lead to 17% difference in cooling consumption and 43% difference in heating consumption compared with using standard outdoor air control settings in EnergyPlus simulation. The effects of the identified uncertainty on fault detection are also discussed.
Die Strategie umsetzen

Korvette, ein Unternehmen, das als Koffer- und Geratediscounter anfing und seinen Verkaufsraum im zweiten Stockwerk einer Fabrikhalle in Manhattan hatte, wurde bereits 1962 zu einer profitablen Discountkette mit einem Dutzend Laden.1 Der Anfangserfolg fuhrte zu einer aggressiven Wachstumsstrategie, die dann im Desaster endete. Das Unternehmen weitete sehr schnell sowohl die Zahl der Laden als auch die Zahl der bedienten Stadte aus, erweiterte die Produktlinie durch Mode, Mobel und Lebensmittel, stattete die Geschafte vornehmer aus.
Assessing student knowledge, confidence, accuracy, and proficiency in providing Medicare Part D assistance

Abstract Purpose To assess the impact of coordinated didactic, simulation-based, and experiential learning on pharmacy students’ knowledge and confidence with Medicare Part D and their accuracy and proficiency with the Medicare Plan Finder Tool. Educational Activity Forty-two pharmacy students participated in a two-semester Medicare Part D elective course in which didactic, simulation-based and experiential learning methods were employed. Students’ knowledge, confidence, accuracy, and proficiency were assessed at three course time points: first day of class, last day of in-class education, and after completion of outreach. Findings Student confidence with Part D and efficiency using the Plan Finder Tool significantly improved at each successive time point (p Summary Basic Part D knowledge improved with the didactic and simulation-based portion of the course. The experiential component improved student confidence and efficiency in helping Medicare beneficiaries.
Prevention of Contraceptive Failure—An Overview

This paper will focus on the prevention of two aspects of this subject: failure to use contraception and contraceptive failure.
Polymeric spatial resolution test patterns for mass spectrometry imaging using nano-thermal analysis with atomic force microscopy.

Rationale As the spatial resolution of mass spectrometry imaging technologies has begun to reach into the nanometer regime, finding readily available or easily made resolution reference materials has become particularly challenging for molecular imaging purposes. This paper describes the fabrication, characterization and use of vertical line array polymeric spatial resolution test patterns for nano-thermal analysis/atomic force microscopy/mass spectrometry chemical imaging. Methods Test patterns of varied line width (0.7 or 1.0 μm) and spacing (0.7 or 1.0 μm) were created in an ~1-μm-thick poly(methyl methacrylate) thin film using electron beam lithography. The patterns were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy topography and nano-thermal analysis/mass spectrometry imaging. Results The efficacy of these polymeric test patterns for the advancement of chemical imaging technique was illustrated by their use to judge the spatial resolution improvement achieved by heating the ionization interface of the current instrument platform. The spatial resolution of the mass spectral chemical images was estimated to be 1.4 μm, based on the ability to statistically distinguish 0.7 μm-wide lines separated by 0.7 μm-wide spacings in those images when the interface cross was heated to 200 oC. Conclusions This work illustrates that e-beam lithography is a viable method to create spatial resolution test patterns in a thin film of high molecular weight polymer to allow unbiased judgment of intra-laboratory advancement and/or inter-laboratory comparison of instrument advances in nano-thermal analysis/atomic force microscopy/mass spectrometry chemical imaging.
A Behavioral Learning Framework of How Emerging Economy Enterprises Upgrade Capabilities

Prior research on organizational capability upgrading has limited its focus on the upgrading means and outcomes, leaving the upgrading process under studied. To fill the gap, in this paper, we theoretically explain and empirically test the process during which firms decide on two alternative capability upgrading directions: capability-deepening or capability-broadening upgrading. We propose that firms choose a certain capability upgrading direction as a deliberate problem-solving process, and that an effective learning mechanism is needed to facilitate the process. Specifically, a firm with high perceived proprietary resource constraints tends to have high engagement in capability-deepening upgrading, while a firm that possesses high ordinary resource slack will have high engagement in capability- broadening upgrading. Further, international benchmarking serves as an important mediating mechanism that guides the firm to a specific capability upgrading pattern to resolve the identified problem. The finding...
Novel natural product therapeutics targeting both inflammation and cancer

Inflammation is recently recognized as one of the hallmarks of human cancer. Chronic inflammatory response plays a critical role in cancer development, progression, metastasis, and resistance to chemotherapy. Conversely, the oncogenic aberrations also generate an inflammatory microenvironment, enabling the development and progression of cancer. The molecular mechanisms of action that are responsible for inflammatory cancer and cancer-associated inflammation are not fully understood due to the complex crosstalk between oncogenic and pro-inflammatory genes. However, molecular mediators that regulate both inflammation and cancer, such as NF-κB and STAT have been considered as promising targets for preventing and treating these diseases. Recent works have further demonstrated an important role of oncogenes (e.g., NFAT1, MDM2) and tumor suppressor genes (e.g., p53) in cancer-related inflammation. Natural products that target these molecular mediators have shown anticancer and anti-inflammatory activities in preclinical and clinical studies. Sesquiterpenoids (STs), a class of novel plant-derived secondary metabolites have attracted great interest in recent years because of their diversity in chemical structures and pharmacological activities. At present, we and other investigators have found that dimeric sesquiterpenoids (DSTs) may exert enhanced activity and binding affinity to molecular targets due to the increased number of alkylating centers and improved conformational flexibility and lipophilicity. Here, we focus our discussion on the activities and mechanisms of action of STs and DSTs in treating inflammation and cancer as well as their structure-activity relationships.
Elucidating the role of plexin D1 in body fat distribution and susceptibility to metabolic disease using a zebrafish model system

Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution of lipid deposited within adipose tissue (AT) - so called body fat distribution (BFD) - is a strong risk factor for NCDs. BFD is highly heritable; however, the genetic basis of BFD is almost entirely unknown. Genome-wide association studies have identified several loci associated with BFD, including at Plexin D1 (PLXND1) - a gene known to modulate angiogenesis. We recently demonstrated that zebrafish homozygous for a null mutation in plxnd1 had a reduced capacity to store lipid in visceral AT (VAT) leading to altered BFD. Moreover, we found that type V collagens were upregulated in plxnd1 mutants, and mediated the inhibitory effect of Plxnd1 on VAT growth. These results strengthen evidence that Plxnd1 influences BFD in human populations, and validate zebrafish as a model to study BFD. However, many pertinent questions remain unanswered. Here we outline potential Plxnd1 mechanisms of action in AT, and describe the genetic architecture at human PLXND1 that is associated with BFD and NCD susceptibility.
Autonomic Mediation of Stress-Related and Anxiety Disorders Using Heart Rate Variability Biofeedback

This article briefly describes a cardiorespiratory type of biofeedback called heart rate variability biofeedback. The rationale for the technique is outlined and the protocol described. Gevirtz (2013) has reviewed the HRVB outcome literature up to 2013. For a more theoretical paper see Lehrer & Gevirtz (2014).
A Comparative Evaluation Study of Growth Conditions for Culturing the Isolates of Campylobacter spp.

Campylobacter is one of the leading causes of foodborne travelers’ diarrhea worldwide. Although a large number cases of campylobacteriosis go undiagnosed or unreported, it is considered as the second most common foodborne illness in the USA affecting over 1.3 million individuals every year. Of various Campylobacter species, C. jejuni, C. coli, and C. lari have been accounted for causing more than 99% of human infections. Thus, there is a need to have efficient isolation method to protect public health on food safety and monitoring the burden of campylobacteriosis. Nevertheless, it is a challenging task as the exposure of environmental stress during isolation process makes Campylobacter species less culturable. Sixteen Campylobacter spp. were used to evaluate the current protocols used in Campylobacter isolation. For optimal recovery, a range of growth media (Bolton, Columbia, Muller Hinton, CVA Campy and mCCDA), incubation temperatures, and additional supplements (including antibiotics) were tested. Blood agars without antibiotics were sufficient for the initial recovery. Afterward, the isolates could grow on agars without any supplements, and in some cases growth was observed in the presence of antibiotics. Incubation at 37 °C was found to be the optimal temperature for the recovery and the growth of most species. Additionally, a food adulteration study was also carried out by artificially contaminating three food matrices that included egg, milk, and infant cereal, with two isolates of C. jejuni and C. coli. Results of this study should provide the insight for culturing and isolation of Campylobacter from food and other sources.
Leber’s Congenital Amaurosis

Leber’s congenital amaurosis has been described as an infantile form of retinitis pigmentosa (RP), although in toddlers and adults it is a separate entity. It is also called hereditary retinal blindness and Leber’s congenital tapetoretinal degeneration.
Major coronary risk factors and death from coronary heart disease: baseline and follow-up mortality data from the Second National Health and Nutrition Examination Survey (NHANES II).

Background Although the major risk factors for coronary heart disease (CHD) are well-established, intense efforts persist in the search for "novel" or "emerging" risk factors because of the notion that as many as half of CHD victims may not have the traditional risk factors. Objective Compare prevalences of major risk factors among persons with fatal CHD in a nationally representative population sample. Methods Baseline data from the Second National Health and Nutrition Examination Survey and 17-year follow-up mortality data were examined for 8,069 adults (3,701 men; 4,368 women) aged 30 to 75 years in 1976–1980. We calculated sex-specific prevalences of hypertension, elevated total cholesterol (≥240 mg/dL), cigarette smoking, and the presence of at least one of these three major risk factors. The relative risk of death from CHD associated with the three major risk factors was calculated in sex-specific multivariable models adjusted for age, race, and education. Results Overall, nearly 75% of US adults had at least one of the three major risk factors. Those who died of CHD, compared to those who did not die of CHD, had respectively, greater prevalences of hypertension (men: 48% vs. 38%; women: 76% vs. 33%). Similarly, persons who had fatal CHD were more likely to have elevated total cholesterol (men: 53% vs. 30%; women: 55% vs. 34%), although the finding was not statistically significant in women. Smoking prevalence was also greater among persons who died of CHD than those who did not for both men (64% vs. 40%) and women (43% vs. 33%). The proportion of persons with at least one of the three major risk factors was significantly ( P ≤0.01) greater among those who died from CHD compared with those who did not (men: 92% vs. 74%; women: 98% vs. 70%). The risk of fatal CHD was 51% lower among men and 71% lower among women with none of the 3 risk factors compared to those with at least one. Had all three major risk factors not occurred, 64% of all CHD deaths among women and 45% of all CHD deaths among men could have been avoided. Conclusions Nine out of ten US adults who died of CHD had at least one of the three major established risk factors. Thus, the notion that many CHD victims do not have the traditional risk factors is a misconception. Policies and strategies that increase the prevalence of a low risk profile are needed, and aggressive efforts in the prevention and control of the major established risk factors remain the key to continued reductions in CHD mortality.
BLOCKAGE OF RNA POLYMERASE AS A POSSIBLE TRIGGER FOR U.V. LIGHT-INDUCED APOPTOSIS

To study the triggering mechanism(s) of the induction of apoptosis following exposure to u.v. light, we used a genetic approach involving cell strains derived from patients with inherited deficiencies in nucleotide excision repair. It was found that cells from patients with Cockayne's syndrome, which are deficient in the processing of u.v.-induced pyrimidine dimers from the transcribed DNA strand, are induced to undergo apoptosis at much lower doses of u.v. light than cells with proficient strand-specific repair. The induction of apoptosis correlated to the induction of p53 and to the inhibition of total RNA and poly(A) mRNA synthesis. We also show that active p53 proteins accumulate following u.v.-irradiation without any apparent requirement for DNA strand breaks or excision repair intermediates. We propose that the blockage of RNA polymerases at DNA lesions in the transcribed strand triggers the induction of a pathway leading to apoptosis. These findings may help explain a long standing enigma of why, despite the DNA repair deficiency, patients with Cockayne's syndrome do not experience an elevated risk for skin cancer since potentially pre-mutagenic cells are eliminated by an easily triggered apoptotic pathway.
The Beginning of the End: On the Origin of Final Cause

Over the last decade or so we have seen a proliferation of models and simulations, largely inspired by biological evolution and cognitive development, in which complex behavior emerges from the local interactions of large populations of simple units. This includes Wolfram’s revival of work based on cellular automata (Wolfram, 1986), the promotion of the neural network paradigm by the Parallel Distributed Processing Research Group (Rumelhart et al., 1986), Holland’s genetic algorithms (Holland, 1975) and classifier systems (Holland, 1986), the logic nets and catalytic reaction systems investigated by Kauffman (1993), and many variations and combinations of these. This work has been done under the various designations of machine learning, artificial life, complexity studies, and evolutionary (or emergent) computation.
Using Spatially Adaptive Filters to Map Late Stage Colorectal Cancer Incidence in Iowa

Disease rates computed for small areas such as zip codes, census tracts or census block groups are known to be unstable because of the small populations at risk. All people in Iowa diagnosed with colorectal cancer between 1993 and 1997 were classified by cancer stage at the time of their first diagnosis. The ratios of the number of late-stage cancers to cancers at all stages were computed for spatial aggregations of circles centered on individual grid points of a regular grid. Late-stage colorectal cancer incidence rates were computed at each grid point by varying the size of the spatial filter until it met a minimum threshold on the total number of colorectal cancer incidences. These different-sized areas are known as spatially adaptive filters. The variances analyzed at grid points showed that the maps produced using spatially adaptive filters gave higher statistical stability in computed rates and greater geographic detail when compared to maps produced using conventional fixed-size filters.
TERESA VILLAVERDE: MAKING OMELETS WITHOUT EGGS

Nearly 50 percent of the students graduating with degrees in film directing programs are women; nearly half of the film audiences around the globe are women; yet, women direct only 8 percent of the films. Like most other industries, men control by men the film industries. An opportunity to direct a film is hard to come by for men. It’s even harder for women. However, when a woman breaks through the glass ceiling, the results are refreshingly satisfying – bringing new perspectives on the female experience and interpersonal relationships. The purpose of this paper is to bring to focus the work of a Portuguese film director, Teresa Villaverde. She began her film career as an actor in A Flor do Mar /Hovering over the Water (1986) and directed her first feature film, A Idade Maior (1991). Since then, she has directed more than a dozen films. For many of these, she has also doubled as writer, editor, cinematographer, and producer. Not only is she a prolific auteur director, her work has earned recognition at international film festivals. The paper describes her professional career and some of the themes she has tackled in her films, e.g., the homeless, the socially alienated, the abused and silenced and the economically unnecessary. Although working with small budgets, she has established herself among the most significant directors in Europe. Relying on existing interviews and reviews, the paper presents Villaverde as a role model for other young filmmakers pursuing careers in cinema.
Task Allocation and the Logic of Research Questions: How Ants Challenge Human Sociobiology

After biologist Deborah Gordon made a series of experimental discoveries in the 1980s, she argued that a change in terminology regarding the division of labor among castes of specialists was needed. Gordon’s investigations of the interactive effects of ants in colonies led her to believe that the established approach Edward O. Wilson had pioneered was biased in a way that made some alternative candidate adaptive explanations invisible. Gordon argued that this was because the term “division of labor” implied a division among specialists that was unwarranted, and proposed “task allocation” as a better description that did not bias research against the alternative causes she had discovered. Gordon’s empirical findings and theoretical proposals also vindicate the initial critics of Wilson’s human sociobiology who have been dismissed as political radicals, but her proposals have been widely misunderstood by many contemporary behavioral ecologists. The terminological and methodological confusions rampant in contemporary discourse can be clarified by applying a framework developed by Elisabeth Lloyd involving an analysis of the constraints imposed by different research questions. Applying this framework will show how the methodological problems involving description raised by the initial critics of Wilson’s human sociobiology extended to his analysis of ants, indicating that they were not challenging Wilson’s naturalistic approach to the study of human evolution, but rather his methods. It will also show how confusion over how Gordon’s proposed research questions have been conflated with the possible answers she has argued ought to be investigated. This in turn will clarify contemporary disputes over her proposal to abandon the term “division of labor.”
Gold foil-based biosensor for the determination of hydrogen peroxide

Hydrogen peroxide ($\text{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$) plays a critical role in the regulation of multifarious physiological processes. We developed a sensor containing a mercaptopropionic acid (MPA) monolayer covalently immobilized with Horseradish peroxidase (HRP) enzyme for the electrochemical detection of hydrogen peroxide ($\textbf{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$). A gold foil substrate was chemically treated with nitric acid and were used as working electrode. Platinum wire and Ag-Ag/Cl were used as counter and reference electrodes, respectively. The acid treated gold electrode with the immobilized enzyme shown to have improved catalytic activity in the reduction of $\textbf{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$. The steady-state current response increases linearly with $\textbf{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$ concentration from 10 $\mu \textbf{M}$ to 9 mM with a low detection limit of 60 $\mu \textbf{M}$ and showed a sensitivity of 0.4 mA/ mM cm$^{\mathbf {2}}$. This electrochemical sensor is demonstrated to be highly selective and sensitive in the presence of interfering analytes. The improved activity and simple preparation method of the electrode makes the MPAHRP modified gold electrode promising for being developed as an attractive robust material for electrochemical $\textbf{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$ sensing.
The Juvenile Idiopathic Arthritis (JIA) Susceptibility Locus, IL2RA, Includes An Intronic Enhancer That Is Attenuated By JIA-Associated Genetic Variants

Like most rheumatic diseases, genetic risk loci for juvenile idiopathic arthritis (JIA) are highly enriched for H3K4me1/H3K27ac histone marks, epigenetic signatures often associated with enhancer function. We sought to determine whether an H3K4me1/H3K27ac region of the JIA risk locus, IL2RA exhibits enhancer function and whether enhancer function is altered by JIA-associated genetic variants. We used a conventional luciferase reporter assay to query enhancer function across an H3K4me1/H3K27ac-marked region within the first intron of the IL2RA gene. We used the same approach to query the effects of 4 single nucleotide polymorphisms (SNPs) on enhancer function. We identified a 657 base pair region within the first intron of IL2RA that demonstrated brisk enhancer function. Enhancer activity was observable in both Jurkat T cells and myeloid HL60 cells. We identified 2 genetic variants, rs117119468 (C->T), and rs12722502 (C->T), that attenuated enhancer activity in this 657 bp region. Conclusions – The JIA-associated risk locus, IL2RA, contains at least one functional enhancer that is active in both lymphoid and myeloid cells. We identified 2 genetic variants that attenuate activity of this enhancer, making them strong candidates as causal variants.
Structural insights into the aPKC regulatory switch mechanism of the human cell polarity protein lethal giant larvae 2.

Metazoan cell polarity is controlled by a set of highly conserved proteins. Lethal giant larvae (Lgl) functions in apical-basal polarity through phosphorylation-dependent interactions with several other proteins as well as the plasma membrane. Phosphorylation of Lgl by atypical protein kinase C (aPKC), a component of the partitioning-defective (Par) complex in epithelial cells, excludes Lgl from the apical membrane, a crucial step in the establishment of epithelial cell polarity. We present the crystal structures of human Lgl2 in both its unphosphorylated and aPKC-phosphorylated states. Lgl2 adopts a double β-propeller structure that is unchanged by aPKC phosphorylation of an unstructured loop in its second β-propeller, ruling out models of phosphorylation-dependent conformational change. We demonstrate that phosphorylation controls the direct binding of purified Lgl2 to negative phospholipids in vitro. We also show that a coil–helix transition of this region that is promoted by phosphatidylinositol 4,5-bisphosphate (PIP2) is also phosphorylation-dependent, implying a highly effective phosphorylative switch for membrane association.
Individual and family-based approaches to increase physical activity in adolescents with intellectual and developmental disabilities: Rationale and design for an 18 month randomized trial

Abstract Adolescents with intellectual and developmental disabilities (IDD) are less physically active and have lower cardiovascular fitness compared with their typically developing peers. This population faces additional barriers to participation in moderate-to-vigorous physical activity (MVPA) such as reliance on parents, lack of peer-support, and lack of inclusive physical activity opportunities. Previous interventions to increase MVPA in adolescents with IDD have met with limited success, at least in part due to requiring parents to transport their adolescent to an exercise facility. We recently developed a remote system to deliver MVPA to groups of adolescents with IDD in their homes via video conferencing on a tablet computer. This approach eliminates the need for transportation and provides social interaction and support from both a health coach and other participants. We will conduct a 18-mo. trial (6 mos. active, 6 mos. maintenance, 6 mos. no-contact follow-up) to compare changes in objectively assessed MVPA in 114 adolescents with IDD randomized to a single level intervention delivered only to the adolescent (AO) or a multi-level intervention delivered to both the adolescent and a parent (A + P). Our primary aim is to compare increases in MVPA (min/d) between the AO and A + P groups from 0 to 6 mos. Secondarily we will compare changes in MVPA, sedentary time, cardiovascular fitness, muscular strength, motor ability, quality of life, and the percentage of adolescents achieving the US recommendation of 60 min. MVPA/d across 18 mos. We will also explore the influence of process variables/participant characteristics on changes in MVPA across 18 mos. NCT registration: NCT03684512
The writing of Spanish majors: A longitudinal analysis of syntactic complexity

Abstract Measures of syntactic complexity are often employed as a way to objectively characterize the development of second language (L2) writing. Complexity measures are eclectic and may be based on length of syntactic unit, relationships between clauses, and variety of syntactic structures. Development in written complexity is of particular interest to university foreign language (FL) departments given its connection to academic discourse. However, few studies explore longitudinal syntactic complexity development in the academic discourse of university FL majors. The present study, part of a larger program assessment project, performs a comprehensive longitudinal analysis of the L2 Spanish written complexity development of three university students over the course of their Spanish major program. A total of 42 academic texts were analyzed for eight complexity measures based on length, inter-clausal relationships, and phrasal/clausal variety. Results show that students develop certain measures more than others, with the greatest growth in length-based measures. Additionally, the importance of inter-learner variability is evident, as participants show clear individual tendencies. Findings are discussed in light of methodological choices, and implications for university FL major programs are explored.
Overcoming challenges in exposure therapy

Abstract Although exposure therapy is an empirically supported treatment for children and adolescents, challenges may arise when implementing exposures in clinical practice. This chapter reviews common challenges that occur when using exposure therapy. Several recommendations are offered to navigate and overcome these challenging situations based on clinical experience and expertise. The chapter concludes with considerations for when challenges persist in treatment.
Evaluation and mitigation of trace 210Pb contamination on copper surfaces

Abstract Clean materials are required to construct and operate many low-background physics experiments. High-purity copper has found broad use because of its physical properties and availability. In this paper, we describe methods to assay and mitigate 210Pb contamination on copper surfaces, such as from exposure to environmental radon or coming from bulk impurities. We evaluated the efficacy of wet etching on commercial samples and observed that 210Po contamination from the copper bulk does not readily pass into solution. During the etch, the polonium appears to trap at the copper–etchant boundary, such that it is effectively concentrated at the copper surface. We observed a different behavior for 210Pb; high-sensitivity measurements of the alpha emissivity versus time indicate the lowest level of 210Pb contamination ever reported for a commercial copper surface: 0 ± 12 nBq/cm 2 (1 σ ). Additionally, we have demonstrated the effectiveness of mitigating trace 210Pb and 210Po surface backgrounds using custom, high-purity electroplating techniques. These approaches were evaluated utilizing assays performed with an XIA UltraLo-1800 alpha spectrometer.
Collection weeding: Innovative processes and tools to ease the burden

Abstract Evaluating collections and ultimately removing content poses a variety of difficult issues, including choosing appropriate deselection criteria, communicating with stakeholders, providing accountability, and managing the overall timetable to finish projects on time. The Science and Engineering librarians at Brigham Young University evaluated their entire print collection of over 350,000 items within one year, significantly reducing the number of items kept on the open shelves and the physical collection footprint. Keys to accomplishing this project were extensive preparation, tracking progress and accountability facilitated by Google Sheets and an interactive GIS stacks map, and stakeholder feedback facilitated by a novel web-based tool. This case study discusses guidelines to follow and pitfalls to avoid for any organization that is considering a large- or small-scale collection evaluation project.
Ethnicity or Religion? A Theory of Identity Choice with Evidence from the Russian North Caucasus

Previous research has either equated religion- and language-based group identities or asserted that their social effects are the same. This article proposes a novel differentiation between religious and ethnic self-identification that accounts for in-group income inequality and the social role of the group. The study argues that ethnicity-based identities tend to be associated with economic activities, thereby increasing the demand for income equality within such groups. Religious identities, on the contrary, are centered around noneconomic activities and have the ideological framework for reconciling material inequalities. The observable implication of this distinction is that the high-, low-, and middle-income categories of the multicultural society will display differential association with ethnic and religious identities. Ethnic groups will have lower in-group income inequality as a result of the exclusion of the poor and the departure of the rich. Religious groups, on the contrary, will have higher in-group income inequality due to the capacity of religion to accommodate both poor and rich. Relevant empirical tests from the ethnically and religiously diverse Russian North Caucasus region indicate support for the proposed theory.
Exploiting nanoscale cooperativity for precision medicine

Precise spatiotemporal control of molecular transport is vital to functional physiological systems. Nature evolved to apply macromolecular cooperativity to achieve precision over systemic delivery of important molecules. In drug delivery, conventional nanocarriers employ inert materials and rely on passive accumulation for tissue targeting and diffusion for drug release. Early clinical studies show these nanodrugs have not delivered the anticipated impact on therapy. Inspired by nature, we propose a design principle that incorporates nanoscale cooperativity and phase transition to sense and amplify physiological signals to improve the therapeutic outcome. Using ultra-pH-sensitive (UPS) nanoparticles as an example, we demonstrate how all-or-nothing protonation cooperativity during micelle assembly/disassembly can be exploited to increase dose accumulation and achieve rapid drug release in acidic microenvironments. In a separate study, we show the effectiveness of a single polymer composition to accomplish cytosolic delivery of tumor antigens with activation of stimulator of interferon genes (STING) in lymph node-resident dendritic cells for cancer immunotherapy. Molecular cooperativity is a hallmark of nanobiology that offers a valuable strategy to functionalize nanomedicine systems to achieve precision medicine.
Methods for the Construction of Recombinant Oncolytic Myxoma Viruses

Myxoma virus (MYXV) has proven to be an effective candidate for oncolytic virotherapy in many preclinical cancer models. As a nonhuman pathogen, MYXV does not need to overcome any preexisting antiviral immunity, and its DNA cannot integrate into the host genome, making it an extremely safe vector. Moreover, the large dsDNA genome of MYXV allows the insertion of multiple transgenes and the design of engineered recombinant oncolytic viruses (OVs) with enhanced immunostimulatory or other desired properties. In this chapter, we describe detailed protocols for the generation and characterization of transgene-armed recombinant MYXV vectors.
Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population.

Background and Purpose: Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a t...