cssi/SciSciGPT-SciSciNet huggingface dataset:
A gating motif in the translocation channel sets the hydrophobicity threshold for signal sequence function

A critical event in protein translocation across the endoplasmic reticulum is the structural transition between the closed and open conformations of Sec61, the eukaryotic translocation channel. Channel opening allows signal sequence insertion into a gap between the N- and C-terminal halves of Sec61. We have identified a gating motif that regulates the transition between the closed and open channel conformations. Polar amino acid substitutions in the gating motif cause a gain-of-function phenotype that permits translocation of precursors with marginally hydrophobic signal sequences. In contrast, hydrophobic substitutions at certain residues in the gating motif cause a protein translocation defect. We conclude that the gating motif establishes the hydrophobicity threshold for functional insertion of a signal sequence into the Sec61 complex, thereby allowing the wild-type translocation channel to discriminate between authentic signal sequences and the less hydrophobic amino acid segments in cytosolic proteins. Bioinformatic analysis indicates that the gating motif is conserved between eubacterial and archaebacterial SecY and eukaryotic Sec61.
Work and Non-Work Physical Activity Predict Real-Time Smoking Level and Urges in Young Adults

INTRODUCTION Physical activity (PA) and smoking are inversely related. However, evidence suggests that some types of PA, namely work-related PA, may show an opposite effect. Despite growing knowledge, there remains a paucity of studies examining the context of these behaviors in naturalistic settings or in young adults, a high-risk group for escalation. METHODS Participants were 188 young adults (mean age = 21.32; 53.2% female; 91% current smokers) who participated in an electronic diary week to assess daily smoking and urges and a PA recall to examine daily PA. PA was coded into non-work-related and work-related activity to examine differential effects. We considered both participants' weekly average PA and their daily deviations from their average. RESULTS Mixed-effects regression models revealed that higher weekly average non-work PA was associated with lower smoking level and urges. Daily deviations in non-work PA did not predict urges; however, increased daily non-work PA relative to participants' weekly average was associated with lower smoking for females but higher levels for males. Regarding work PA, only higher weekly average work PA was associated with higher smoking level for both genders; work PA did not predict urges. CONCLUSIONS Results extend previous literature by documenting differential associations between non-work and work PA and young adult smoking and suggest that young adults engaged in work PA should be considered a high-risk group for escalation. Findings provide theoretical and clinical implications for the use of PA in intervention and highlight the necessity of considering PA as a multidimensional construct when examining its links to health behavior.
PGE2 secretion by the conceptus and binding by non‐pregnant endometrium in the horse

Summary Conceptus PGE2 secretion was determined by incubating equine conceptuses (7/day) in vitro for 24 h. Day-11, -13 and -15 conceptuses secreted (mean ± sem) 91.2 ± 23.7, 92.8 ± 15.9 and 170.8 ± 24.9 ng PGE2/24 h, respectively. Day-15 conceptuses secreted more (P 0.10) in the dissociation constant between days. These results demonstrate that equine conceptuses secrete PGE2, and non-pregnant equine endometrium specifically binds PGE2 during the period of maintenance of the corpus luteum.
Development of Hydrogel-Based Keratoprostheses: A Materials Perspective

Research and development of artificial corneas (keratoprostheses) in recent years have evolved from the use of rigid hydrophobic materials such as plastics and rubbers to hydrophilic, water-swollen hydrogels engineered to support not only peripheral tissue integration but also glucose diffusion and surface epithelialization. The advent of the AlphaCor core-and-skirt hydrogel keratoprosthesis has paved the way for a host of new approaches based on hydrogels and other soft materials that encompass a variety of materials preparation strategies, from synthetic homopolymers and copolymers to collagen-based bio-copolymers and, finally, interpenetrating polymer networks. Each approach represents a unique strategy toward the same goal: to develop a new hydrogel that mimics the important properties of natural donor corneas. We provide a critical review of these approaches from a materials perspective and discuss recent experimental results. While formidable technical hurdles still need to be overcome, the rapid progress that has been made by investigators with these approaches is indicative that a synthetic donor cornea capable of surface epithelialization is now closer to becoming a clinical reality.
Liquidity of Corporate Bonds

This paper examines the liquidity of corporate bonds. Using transaction-level data for a broad cross-section of corporate bonds from 2003 through 2007, we construct a measure of illiquidity by estimating the magnitude of price reversals in corporate bonds. We flnd the illiquidity in corporate bonds to be signiflcant and substantially more severe than what can be explained by bid-ask bounce. We establish a robust connection between our illiquidity measure and liquidity-related bond characteristics. In particular, it is higher for older and smaller bonds and bonds with smaller average trade sizes and higher idiosyncratic return volatility. Aggregating our illiquidity measure across bonds, we flnd strong commonality in the time variation of bond illiquidity, which rises sharply during market crises and reaches an all-time high during the recent sub-prime mortgage crisis. Moreover, monthly changes in aggregate illiquidity are strongly related to changes in the CBOE VIX Index. We also flnd a robust positive relation between our illiquidity measure and bond yield spreads that is economically signiflcant.
Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions.

Basic fibroblast growth factor (bFGF) supports the survival of neurons from many regions of the E18 fetal rat brain. Survival was significantly increased for neurons derived from the hippocampus, entorhinal cortex (EC), frontal cortex, parietal cortex (PC), occipital cortex, striatum, septum, and thalamus, but not from the subiculum (Sb). The proportion of neurons rescued by bFGF varied among brain regions, suggesting the existence of subpopulations of responsive neurons. Like hippocampal neurons, neurons from the EC and PC required about 1 pM bFGF (10–20 pg/ml) for half-maximal response; striatal neurons, in contrast, required about 3 pM bFGF. Neurite outgrowth after 24 hr exposure was significantly increased for neurons from the hippocampus, EC, and PC, while striatal neurons had only a marginal response. Although bFGF stimulated some astrocytic proliferation in the cultures, glial contamination was maintained at 2% or less. Acidic FGF (aFGF) supported smaller numbers of neurons from each region, although it significantly increased survival of neurons from hippocampus, EC, PC, striatum, and Sb. The concentration required for half-maximal survival was around 100–300 pM (2–5 ng/ml). It appears that bFGF and aFGF are potent trophic factors for many populations of CNS neurons and could potentially play a significant role in nervous system development.
The redesign of a quantitative literacy class: student responses to a lab-based format

The purpose of this study was to observe students´retention, success and attitudes towards mathematics in a community college quantitative literacy course, taught in a lab-based format. The redesigned course implemented the daily use of Microsoft Excel in the classroom demonstrations, group activities and infividual assignments, and utilized data from many fields of study. Results showed statistically significant growth in attitudes towards real-world application problems, the use of computers in mathematics, and the consideration of taking additional mathematics courses. There was also marginally significant growth in students´attitudes towards the relevance and utility of mathematics. Higher retention and success rates in the redesigned course were also observed, although those rates were not found to be statistically significant.
A generalization of the rotation matrix and related results

Abstract A new generalization of the rotation group involving a skew circulant matrix is given. Using the exponential map, a unified treatment is given to this generalization and to one due to Ungar. The special functions associated with the corresponding Lie groups are the trigonometric and hyperbolic functions of order n . Infinitesimal generators and invariants under the corresponding transformations are also obtained. A general theorem on linear transformations involving circulant and skew circulant matrices is also given.
Factors Affecting Continued Use of Social Media

This research paper focuses on factors which affect the continued use of social media technology. Using the Technology Acceptance Model, the Theory of Reasoned Action and the Theory of Planned Behavior, a research model was constructed which focused on a set of core constructs, including Perceived Usefulness, Social Norms, Self-Efficacy, and Attitudes and their overall impact on users Continuous Intent to Use social media technologies. Results will be shared with conference participants.
Organotypic Endothelial Cell Surface Molecules Mediate Organ Preference of Metastasis

Metastases are tumor colonies that develop in distant, often multiple organ sites by dissemination from a malignant primary tumor. Although the most frequent organ sites of distant metastases are the first organs encountered by blood-borne tumor cells, many cancers metastasize to sites which are unrelated to the initial organ entered by circulating tumor cells and, thus, display unique organ colonization patterns that do not fit simple, anatomical-mechanical trapping theories of tumor cell dissemination.1–7 For example, breast adenocarcinomas metastasize frequently to liver, bone, brain, and adrenals, in addition to the expected, high incidence of metastasis to the lungs, and carcinomas of the prostate metastasize most often to bone. This nonrandom pattern of metastasis was first described by Paget,8 who championed the “seed and soil” hypothesis of the metastatic spread. He postulated that gross tumor development was a consequence of the provision of a fertile environment (the soil) in which compatible tumor cells (the seeds) could proliferate.4 Numerous studies on the mechanisms of preferential metastasis have since shown that tumor cell implantation, invasion, survival, and growth at secondary organ sites depend upon a number of tumor cell and host characteristics that provide the proper cellular and stromal environment for metastasis to develop.9–16
X-radiation and Growth Substances as Affectin Plant Primordial Tissues

Since little attention has been given to the primordial regions of plants as influenced by X-radiation and chemical growth-promoting substances the author has carried out experiments to determine effects of these agencies on growing points. Snow1 observed that heteroauxin applied to the growing regions of certain plants caused union of leaf primordia, and Bausor2 describes the development of root primordia on stems, petioles, and apical meristem when these parts are treated with beta-naphthoxyacetic acid.In the present study, seedlings of sunflower (Helianthus annuus), zinnia (Zinnia elcgans), and tomato (Lycopersicum esculentum) were given moderate X-ray doses (2300 to 2500 r-units for sunflower and zinnia and up to 3000 r-units for tomato). Plants were stunted, and showed rough, warty, and abnormally-shaped leaves, with fasciation of leaves and of stems and frequent fusion of leaf primordia, as previously reported by Johnson.3 Often, a few weeks after treatment, the meristematic region was divided into ...
Microstructure-Dependent Nucleation in Atomic Layer Deposition of Pt on TiO2

The effects of TiO2 microstructure on Pt nucleation and on formation of continuous ultrathin Pt films by atomic layer deposition (ALD) were investigated. Pt was deposited by a metalorganic Pt precursor ((methylcyclopentadienyl)trimethylplatinum) and air as a counter reactant on in situ grown ALD TiO2 surfaces. For the same number of Pt ALD cycles, the Pt surface coverage was found to depend on the thickness of the underlying TiO2. From X-ray diffraction (XRD) analysis, it was found that the amorphous microstructure of as-deposited TiO2 transforms into anatase microstructure because of an annealing effect at the elevated Pt ALD temperature, and that this effect is a function of TiO2 thickness. Transmission electron microscopy revealed that continuous growth of ALD Pt occurs on anatase TiO2 whereas island growth occurs on amorphous TiO2. These results indicate that Pt nucleation is significantly affected by the microstructure of TiO2. Effects beyond surface hydrophilicity, such as a catalytic effect, are ne...
Application of Fuzzy Control in Managment of Construction Ma-chine Spare Parts

In order to study the decision-making problem of inventory and storage mode of construction machine spare parts,the decision on variety and inventory is made,and the requirement and order strategy model of construc- tion machine spare parts is established based on the theories of fuzzy control.It is proved that this method is the sc entific basis of the management of construction machine spare parts
16 RISK FACTORS LEADING TO SEVERE RESPIRATORY SYNCYTIAL VIRUS INFECTION IN FULL-TERM INFANTS.

Prematurity, chronic lung disease, and congenital heart disease have been identified as risk factors for severe respiratory syncytial virus (RSV) infection and hospitalization. Objective To characterize additional risk factors that lead to severe RSV infection in infants > 36 weeks gestation. Methods The medical records of all children less than 2 years of age hospitalized for RSV infection during 2 RSV seasons (2003-2004 and 2004-2005) were reviewed. The data recorded included age, length of hospital stay, intensive care unit (PICU) stay, and oxygen and ventilation requirement. Any risk factors that may have led to hospitalization or more severe disease were recorded. Results A total of 106 infants > 35 weeks9 gestation were identified. The table below summarizes severity of RSV infections according to some of the risk factors that were identified: Underlying diseases included those with congenital anomalies, Down syndrome, and neuromuscular disease. Ten patients had overlapping risk factors (ie, some had asthma as well as tobacco exposure). Conclusions Although having school-aged siblings predisposed to a higher frequency of RSV hospitalizations, having an underlying disease, such as Down syndrome or congenital heart disease, predisposed to a more severe course of RSV hospitalization as indicated by the much longer length of hospital and PICU stay. Patients exposed to passive smoking appear to have the mildest hospitalization course with virtually no PICU admission. Interestingly, patients with reactive airway disease were much older and also tended to have a milder hospitalization course. In general, patients with no risk factors for RSV infection were much younger than the others and had a more severe RSV course. The 10 patients with multiple risk factors did not have a worse hospital course compared with those with a single risk factor.
Reform of Legal Institutions

Jerome Frank was interested not only in describing and analyzing our judicial institutions but also in proposing positive legal reforms. Because he viewed the trial courts as the most important and most neglected aspect of our court system, he devoted much attention to their improvement. Failure to achieve just solutions to individual cases, Frank maintained, was primarily caused by weaknesses in the fact-finding ability of our lowest courts.1
Preoperative Planning and Prosthetic Selection

As is true for all surgical procedures, a careful and complete preoperative preparation is essential to the ultimate success of a total knee replacement. Most orthopaedic surgeons are aware of this fact and have at least a vague idea of what they must do to prepare for an upcoming total knee procedure. However, if the total knee procedure is to be successfully and safely carried out, preoperative preparation must also be carried out by the patient and his or her family and by the hospital at which the procedure is to be performed The surgeon is responsible for initiating and guiding this preparation by the patient and the hospital. The surgeon must recognize and acknowledge the importance of this preparation and should be prepared to assure that the patient and hospital are as ready for the upcoming total knee arthroplasty as he or she is. In this chapter, I will discuss the preparation that the surgeon, patient and hospital should carry out prior to the performance of a primary or revision total knee arthroplasty
Utilization of 4T score to determine the pretest probability of heparin-induced thrombocytopenia in a community hospital in upstate New York.

Background : Thrombocytopenia is common in hospitalized patients. Heparin-induced thrombocytopenia (HIT) is a life-threatening condition which can lead to extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by 4T score and immunoassays through testing for anti-PF4/heparin antibodies. Clinical practice guidelines published by the American Society of Hematology in 2013 recommended use of the 4T score before ordering the immunoassays as a measure of pretest probability. The purpose of this study was to evaluate the utilization of 4T score before ordering anti-PF4/heparin antibodies at Unity Hospital. Methods : We did a retrospective chart review for patients who are 18 years or older, admitted to Unity Hospital between July 1, 2013, and December 31, 2014, and had anti-PF4/heparin antibodies ordered. Subjects who had prior history of HIT or had end-stage renal disease on hemodialysis were excluded. After calculating 4T score retrospectively, we calculated the proportion of patients who had 4T score documented prior to ELISA testing and proportion of ELISA tests, which were not indicated due to a 4T score less than or equal to 3 using Minitab 16. Results : Review of 123 patients, with an average age of 69.4 years, showed that testing was indicated in 18 patients. Six subjects had positive results, and testing was indicated in all of them. 4T score was documented in three patients. This quality improvement study showed that 4T score documentation rate at Unity Hospital is 2.4%. Anti-PF4/heparin antibody testing was indicated in 14.6%. This test is being overused in thrombocytopenia work up at Unity Hospital, costing $9,345. The topic was reviewed for residents. A prompt and calculator for 4T score were added to electronic medical records before ordering the test as a step to improve high value care.
Cities, museums and soft power

When you think of a museum, what image comes to mind? Perhaps you think of a specific institution, such as the nearby art museum, historic house, or zoo, with whom you connect onsite or online. Or,...
Prevention of Early Substance Use Mediates, and Variation at SLC6A4 Moderates, SAAF Intervention Effects on OXTR Methylation

The Strong African American Family (SAAF) program has been shown to have a variety of short and long-term benefits for participating youth and families. However, biological mechanisms potentially influencing long-term effects on resilience in young adulthood have not been examined. In the current investigation, we examine the effects of SAAF on methylation of the OXTR gene in young adulthood, focusing on a regulatory region previously identified to be both responsive to stress and implicated in resilience. Using the subsample of participants from the original study for whom methylation data was available (N = 388), we replicated the previously reported G × E effect on prevention of early substance use and then examined whether there would also be a moderated effect on OXTR methylation in early adulthood, with “s” allele carriers, but not “LL” participants, showing a significant indirect effect of SAAF on OXTR methylation. Results suggest that for susceptible youth (i.e., “s” allele carriers), preventive intervention may “get under the skin,” in a manner potentially beneficial for long-term outcomes. Implications for examination of OXTR methylation in future prevention research are discussed.
Defining deer overabundance and threats to forest communities: From individual plants to landscape structure

AbstractChanges in habitat and reduction in predation and hunting pressure are two primary causes of high-density populations of white-tailed deer (Odocoileus virginianus) in many areas of eastern North America. Despite increasing recognition of the major effects deer exert on forest communities, deciding when deer are overabundant remains a major challenge to managers charged with conserving native plant communities. In this context, we define overabundance as a condition where deer are causing the local extinction of a native plant species. Because this definition is difficult to apply from a management perspective, we outline an approach using native understory forbs. Indicator species are selected based on combined criteria of palatability to deer, leaf and flower morphology, and demographic characteristics. Four indices related to plant population viability are derived from understory survey data: flowering rate, mean stem height, stage-class distribution, and deer browsing pressure. We apply this an...
National Rates, Causes, Risk Factors, and Outcomes Associated With 30-Day and 90-Day Readmissions Following Degenerative Posterior Cervical Spine Surgery Utilizing the Nationwide Readmissions Database.

BACKGROUND Hospital readmissions have profound financial and clinical impacts. Analyses of 30-day readmissions following spine surgery have been previously reported utilizing administrative databases. However, time periods outside the initial 30 days have not been well studied. Furthermore, these databases have limitations regarding coding and institutional crossover. OBJECTIVE The authors sought to analyze 30-day and 90-day readmission rates and risk factors using the Nationwide Readmissions Database (NRD) in a retrospective cohort receiving elective, posterior cervical spine surgery for degenerative conditions. METHODS NRD is a new source containing approximately 50% of US hospitalizations, with patient-linkage numbers to longitudinally track patients. Patients 18 years of age or older were identified. Preoperative characteristics, demographics, and surgical characteristics were chosen for predictor variables. Thirty-day and 90-day readmission rates were calculated. Statistical analysis was completed using SPSS v.23 software via univariate and multivariate analyses. RESULTS Between January and September 2013, a total of 29 990 patients were identified. Readmission rates for 30- and 90-days were 5.4% and 10.0%, respectively. The most common reason for readmission during 30-day and 90-day periods was complications of surgical and/or medical care (31.0% vs 21.9%, respectively). The strongest risk factors for 30-day readmission included wound dehiscence, weekend admission at index hospitalization, coagulopathy, and incidental durotomy. The strongest risk factors for 90-day readmission included thromboembolic complications, postoperative hemorrhage, and comorbidities. CONCLUSION Identification of predictors of readmission is important to allow for changes in perioperative management to potentially reduce readmissions and improve outcomes. Additionally, knowledge about readmission risk factors allows for preoperative counseling.
Vascular Diseases of the Spleen: A Review.

Vascular diseases of the spleen are relatively uncommon in the clinical practice. However, the reported incidence has been progressively increasing, probably due to advances in the imaging modalities used to detect them. This disease condition often presents with non-specific clinical manifestations, but can be associated with significant morbidity and mortality. This review article aims to provide updated clinical information on the different vascular diseases of the splenic vasculature—splenic vein thrombosis, splenic vein aneurysm, splenic artery aneurysm, splenic arteriovenous fistula, and spontaneous splenorenal shunt—in order to aid clinicians in early diagnosis and management.
Abstract 29: Heme Levels Are Increased in the Hearts of Patients with End-Stage Heart Failure

Introduction: Diseases of iron imbalance can cause cardiomyopathy, as observed in hereditary hemochromatosis or Friedreich’s ataxia. However, the iron status of a failing heart has not been systematically examined. Results: The iron levels were quantified in ten hearts from human patients with end-stage cardiomyopathy and ten unmatched healthy control hearts. Total cellular and cytosolic non-heme iron levels were significantly reduced in failing hearts; however, there was a 2-fold increase in cytosolic heme levels in heart failure, as measured by the total protoporphyrin IX (PPIX) content. The amount of iron-free PPIX was low and did not differ between the two groups, suggesting that the majority of PPIX is complexed with iron to form heme, and thus our assay accurately estimates heme levels in the heart. To study the mechanism for the increased heme content in failing hearts, we examined the expression of genes involved in heme and iron homeostasis. Consistent with elevated heme, there was a decrease in the levels of the cellular iron importer (transferrin receptor 1 orTfR1) and the first enzyme in heme synthesis (δ-aminolevulinic acid synthase 1 or ALAS1), both of which are negatively regulated by heme. Other genes involved in heme synthesis, iron incorporation into PPIX, and heme degradation were not affected. However, we noted a significant increase in the mRNA and protein levels of ALAS2 in the failing hearts. ALAS2 is normally expressed in hemoatopoietic cells and displays very low expression in the heart. Its induction in the setting of heart failure provides a possible explanation for increased heme levels. We then assessed whether increase in ALA and heme in failing hearts is associated with generation of reactive oxygen species (ROS). Addition of exogenous ALA led to a four-fold increase in ROS, while incubation with hemin have doubled ROS levels in these cells, suggesting that augmentation of heme synthesis may exacerbate heart failure by increasing the oxidative stress. Conclusions: Our results suggest that heme levels are increased in human hearts with end-stage cardiomyopathy, possibly through the induction of ALAS2 expression. The elevated heme levels may exacerbate heart failure by increased production of ROS.
Is retained bone debris in cannulated orthopedic instruments sterile after autoclaving

Aims Cannulated surgical instruments may retain biologic debris after routine cleaning and sterilization. Residual debris after cleaning is assumed to be sterile; however, there is no experimental basis for this assumption. The purpose of this study was to determine the sterility of retained biodebris found within cannulated surgical instruments after autoclave sterilization. Materials and Methods Fifteen cannulated drill bits were used to drill pig scapulae to create a plug of bone that was exposed to a mixture of Bacillus cereus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus for 60, 120, or 180 minutes prior to sterilization. The drill bits were autoclave sterilized using standard settings. The “sterilized” bone cores were then incubated in solution and streak-plated on blood agar. Results All 3 positive controls were positive for the experimental bacteria. Two negative controls were positive for contaminant bacteria. A B. cereus strain was recovered from 1 of the experimental group drill bits in the 180-minute group. Pulsed-field gel electrophoresis confirmed that the recovered B. cereus strain was identical to the experimental inoculate. Conclusion Retained biodebris in cannulated drills may not be sterile after standard autoclave sterilization. In addition, delay of surgical instrument reprocessing may increase the risk of resistant contamination.
The Superconductive Critical Magnetic Field of Beryllium

We have measured the temperature dependence of the superconductive critical magnetic field of three samples of beryllium from three different sources. The irregular geometric shape of one sample prevented a complete analysis of the data, but the data for the other two samples were well represented by the BCS model of superconductivity. The values of T c and H c (0) are found to be sample dependent. For the purest sample studied, T c =24.34±0.02 mK, H c (0)=107.7±0.2 μT and (γ/V)=32.9±0.3 μJ/cm3 K2. By a very small extrapolation of the data as a function of purity, it is inferred that the critical parameters for pure Be are: T c =24.38±0.02 mK, H c (0)=107.9 μT±0.2 μT and (γ/V)=33.0±0.3 μJ/cm3 K2.
Assessment of the Hepatic Vessels with MDCT

Multidetector computed tomography angiography (MDCTA) is an established, noninvasive and effective imaging method to evaluate the liver primarily for neoplasm staging and presurgical planning. However, its role has also extended into variety of other clinical indications. Technological advances in MDCT scanners and post processing now offer new opportunities with CTA but the challenges of protocol optimization should be confronted. In this article, we will focus on the technical details with MDCTA protocols for the liver and discuss the common pathologic conditions where CTA is now considered integral to patient management.
The chemokine system: a possible therapeutic target in acute graft versus host disease.

Allogeneic hematopoetic stem cell transplantation often presents the only chance for cure in a number of malignant and nonmalignant hematologic diseases. However, its beneficial effects are counterweighed by the development of potentially lethal complications, most importantly the development of acute and chronic graft-vs.-host disease (GVHD). Alloantigen-reactive immune responses mediate injury and destruction of GVHD target organs, including the gastrointestinal tract, the liver, the skin, and the lung. Donor leukocyte infiltration into the respective tissues is orchestrated by interactions between chemokines and chemokine receptors, which will be reviewed using a basic science – clinical comparative approach.
Abstract 5309: beta-Arrestin 1 (bArr1) and Ankyrin 2 (ANK2) Regulate Cav1.2 Trafficking through Complex G Protein Mediated Signaling

Mechanisms governing the trafficking of cardiac voltage dependent calcium channels (Ca v 1.2) remain largely unknown. We have previously shown that neuronal calcium channels are internalized into clathrin coated vesicles upon G protein coupled receptor (GPCR) activation. Here, we hypothesize that GPCR mediated signaling regulate Ca v 1.2 trafficking and surface expression through interaction with cytoskeletal and signaling molecules. Methods : Sequential immunoprecipitation in adult rat cardiomyocytes was used to investigate the interaction between Ca v 1.2, cytoskeletal and signaling molecules. Live cell imaging and immunofluorescence microscopy were used to measure changes in the cellular localization of Ca v 1.2 and these proteins upon activation of GPCR signaling. Results : Cav1.2 interacts with ANK2, βArr1 and spectrin. Sustained β adrenergic receptor (βAR) activation increases Cav1.2/spectrin and decreases Ca v 1.2/ANK2 and Ca v 1.2/βArr1 interactions. Sustained βAR activation induces rapid ( v 1.2/ANK2 co-localization is markedly reduced (−58% p v 1.2/ANK2 interaction decreases (−40±12%, p v 1.2 internalization suggesting that G i/o mediates this response. Similarly, Src kinase inhibition reduces (by 90%) Ca v 1.2 internalization. Differential labeling of pre-existing Ca v 1.2 at the cell membrane and newly inserted Ca v 1.2 using fluorophore conjugated dihydropyridines reveal that activation of G i/o proteins underlies Ca v 1.2 internalization and insertion. In contrast, activation of the muscarinic M2 receptor (10μM carbachol) causes only insertion of new channels (n=14) and fails to alter the association of Ca v 1.2 with ANK2 and spectrin. Finally PI3 kinase inhibition (10nM wortmannin) prevents Ca v 1.2 membrane insertion. Conclusions : Our findings reveal novel signaling mechanisms that regulate Ca v 1.2 trafficking, internalization and membrane insertion in a receptor subtype dependent manner. These mechanisms may be central to pathologies associated with a hyperadrenergic state. This research has received full or partial funding support from the American Heart Association, AHA National Center.
When should one stop cholinesterase inhibitors in patients with Alzheimer's disease?

To submit questions for this regular feature, please send them to the Journal of Psychiatry & Neuroscience / Revue de psychiatrie & de neuroscience, Royal Ottawa Hospital, LG 2044, 1145 ave. Carling Ave., Ottawa ON K1Z 7K4, Canada; fax 613 722-5871. Please include details of any relevant case and your name, address, telephone and fax numbers as well as your email address. The information in this column is not intended as a definitive treatment strategy but as a suggested approach for clinicians treating patients with similar histories. Individual cases may vary and should be evaluated carefully before treatment is provided.
Ontogeny of the Receptor and Responsiveness to Estrogen in the Genital Tract of the Chick Embryo

ABSTRACT In the embryonic genital tract of the chick, the appearance of estrogen receptor is an early event. Estrogen receptor is detectable in the cytoplasm of the Mullerian duct on day 8 of embryo development. The concentration of cytoplasmic receptor was maximal on day 12 of incubation and remained at that level until hatching. The receptor was capable of translocation into the nucleus as early as day 10 of incubation. The nuclear capacity for binding the estrogen-receptor complex increased linearly from day 10 to a maximum at day 15, which was maintained until hatching. Development of estrogen binding capacity by chromatin in the genital tract paralleled the increase in nuclear binding capacity and maturation of chromatin composition. The capacity for estrogen binding during chromatin development was maximal at day 15 of development; the chromatin binding sites then represented 14–18% of the total nuclear binding sites. These observations indicate that the apparatus for responding to estrogen in the genital tract of chick embryos reaches its full capacity 5 to 6 days before hatching. The following parameters were found to be maximally responsive to estrogen stimulation (reaching the level in newborn) at day 15–21 of embryonic development: a) Chromatin template capacity and RNA chain initiation sites, b) The activity of ornithine decarboxylase, the rate-limiting enzyme for polyamine synthesis, c) The number of tubular gland cells. The following biochemical events were found to be independent of the concentration of estrogen receptor: a) The synthesis of mRNAov in tubular gland cells in response to estrogen, which did not reach its maximal rate in the embryonic stage, b) The synthesis of ovalbumin, which continued to rise throughout embryonic development. (This study was supported by NIH grants HD-08218, HD-09467 and AG-00523.)
ST-ELEVATED MYOCARDIAL INFARCTION IN A LEFT MAIN CORONARY ARTERY: A CLINICAL DILEMMA

Management of an acute left main coronary artery (LMCA) thrombus is challenging. A 39 year-old healthy Russian male presented with 24h of chest pain radiating down his left arm associated with dyspnea and diaphoresis. He was in mild distress. Electrocardiogram revealed an evolving anterolateral ST-
Training Non-Native Consonant Production with Perceptual and Articulatory Cues.

Background/aims Adult learners often struggle to produce novel phonemes in a second language and lack clear articulatory targets. This study investigates the combined efficacy of perceptual and articulatory training, the latter involving explicit instruction about tongue position and laryngeal control, for the production of non-native phonemes. Methods Native English speakers were trained on a series of Hindi coronal stop consonants, with production assessed before, during, and after training sessions, on the basis of acoustic cues to place of articulation and voicing. Results Improvement in production was most apparent during artic u-latory training, when cues to target articulation were available to learners. Some improvements were maintained after training was concluded. Conclusion Articu-latory training can contribute useful cues to pronunciation for early learners. Improvement in acquisition of targets varies in stability across learners and targets.
Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease.

Abstract Background To circumvent the challenges associated with delivering large compounds directly to the brain for the treatment of Parkinson's disease (PD), non-invasive procedures utilizing smaller molecules with protective and/or restorative actions on dopaminergic neurons are needed. New method We developed a methodology for evaluating the effects of a synthetic neuroactive peptide, DNSP-11, on the nigrostriatal system using repeated intranasal delivery in both normal and a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. Results Normal rats repeatedly administered varying doses of DNSP-11 intranasally for 3 weeks exhibited a significant increase in dopamine (DA) turnover in both the striatum and substantia nigra (SN) at 300 μg, suggestive of a stimulative effect of the dopaminergic system. Additionally, a protective effect was observed following repeated intranasal administration in 6-OHDA lesioned rats, as suggested by: a significant decrease in d-amphetamine-induced rotation at 2 weeks; a decrease in DA turnover in the lesioned striatum; and an increased sparing of tyrosine hydroxylase (TH) positive (+) neurons in a specific sub-region of the lesioned substantia nigra pars compacta (SNpc). Finally, tracer studies showed 125I-DNSP-11 distributed diffusely throughout the brain, including the striatum and SN, as quickly as 30 min after a single intranasal dose. Comparison with existing methods The results of bilateral intranasal administration of DNSP-11 are compared to our unilateral single infusion studies to the brain in rats. Conclusions These studies support that DNSP-11 can be delivered intranasally and maintain its neuroactive properties in both normal rats and in a unilateral 6-OHDA rat model of PD.
Inguinal hernias in children.

Background An inguinal hernia is one of the most common paediatric surgical presentations in a primary care setting. Hernias can present in multiple ways, ranging from an emergency such as a strangulated hernia to a less urgent reducible hernia. Objective The aim of this article is to aid in appropriate diagnosis and management of hernias in children. The article also provides useful tips for hernia reduction that are especially beneficial in the primary care setting and assist with the identification of hernias that require urgent referral. Discussion Recognising the signs of a hernia containing compromised contents is essential to prevent serious complications such as intestinal perforation, testicular atrophy and ovarian damage. Other common conditions such as hydrocoele and undescended testis are sometimes confused with an inguinal hernia. Young patients under the age of three months and patients with concern for compromised contents require urgent referral. Recent evidence regarding controversial issues in inguinal hernia repair such as the role of laparoscopy and the relevance of a contralateral patent internal inguinal ring will be discussed.
Accuracy and Reliability of Commercial Wrist-Worn Pulse Oximeter During Normobaric Hypoxia Exposure Under Resting Conditions.

Purpose: The present study analyzed peripheral blood oxygen saturation (SpO2) and heart rate (HR) measurements taken on the Garmin fēnix® 5X Plus watch, comparing them to measurements taken on a st...
[Kawasaki disease - a new manifestation of COVID-19 in children]

Since the outbreak of coronavirus disease 2019 (COVID-19) in Europe and America, the incidence of Kawasaki disease has significantly increased, which has aroused concern among pediatricians and parents. COVID-19 can cause inflammation reactions of multiple organs, which is similar to the systemic vasculitis of Kawasaki disease, and even COVID-19 can cause skin rash on the extremities of the limbs, which is also similar to Kawasaki disease. The cause of Kawasaki disease is currently unclear, and it cannot be ruled out that COVID-19 is associated with an increased incidence of Kawasaki disease. Therefore, during the epidemic of COVID-19, if children have symptoms similar to Kawasaki disease, intravenous immunoglobulin is recommended as early as possible to reduce the incidence of coronary artery lesions.
Intertemporal Risk and the Cross Section of Expected Stock Returns

Existing portfolio-level evidence about the Intertemporal Capital Asset Pricing Model (ICAPM) of Merton (1973) and Campbell (1996) is mixed. To avoid problems associated with the use of portfolios to test asset-pricing models, I develop a new firm-level approach to test the ICAPM while overcoming potential econometric issues with using individual stocks. The ICAPM performs quite well, explaining a substantial portion of the variation in average returns left unexplained by the CAPM. Moreover, investors accept lower returns on assets that hedge against adverse shifts in the investment opportunity set, consistent with equilibrium ICAPM predictions. I also investigate the conjecture that the SMB and HML factors of the Fama-French (1993) model proxy for intertemporal risk. The empirical evidence suggests the Fama-French model is not an ICAPM model.
Increases in Risky Drinking During the COVID-19 Pandemic Assessed via Longitudinal Cohort Design: Associations With Racial Tensions, Financial Distress, Psychological Distress and Virus-Related Fears.

BACKGROUND: The COVID-19 pandemic has created disruptions to daily life resulting in wide-spread unemployment and psychological distress. Recent studies have reported high rates of alcohol use during this time; however, longitudinal data remain scarce and factors associated with increases in high-risk drinking observed over time are unknown. AIMS: The current study examined changes in high-risk drinking patterns across four 7-day observation periods, prior to and following a university wide campus closure. Additionally, factors associated with changes in alcohol use patterns were examined including financial distress, psychological distress, impact of racial tensions and virus-related fears. METHOD: Students (N = 1001) in the Midwestern USA completed repeated assessments between March and June 2020. Each survey included a timeline follow-back measure of alcohol use. Pandemic-related distress spanning several factors was assessed at the final follow-up. RESULTS: Risky drinking patterns increased significantly over time. Overall, psychological distress and impact of racial tensions were associated with higher rates of risky drinking, whereas COVID-19-related fears were associated with lower rates. However, only financial-related distress was associated with an increase in risky drinking patterns over time. CONCLUSIONS: Increased risky drinking patterns observed in the current study may signal problems that are likely to persist even after the direct impact of the COVID-19 pandemic on daily life ends. Individuals experiencing financial distress may represent a particularly high-risk group. Interventions targeting the cross-section of job loss, financial stress and problematic alcohol use will be important to identify.
A Simple Test for the nth term of a Series to Approach Zero

(1988). A Simple Test for the nth term of a Series to Approach Zero. The American Mathematical Monthly: Vol. 95, No. 10, pp. 942-942.
Using Article 20

Using Article 20 is a companion piece to Strengthening Article 20, 38 U.S.F. L. REV. 701 (2004). Assuming article 20 can be invigorated (see Strengthening Article 20), this article sets forth the specific argument attorneys would make under article 20 for domestic violence survivors. It argues that United States’ law (U.S. statutory law, case law, state constitutional law, federal constitutional law, and U.S. treaty obligations) recognizes the impermissibility of making a woman choose between her life and her child; this is the choice inflicted on a domestic violence victim by the Hague Convention. Referring to this law, it suggests that the fundamental principles relating to the protection of human rights in the United States should prohibit a U.S. court from returning a domestic violence victim’s child. The article uses a hypothetical problem to set up the analysis and addresses a few of the relevant doctrinal issues.
Socioeconomic differentials in fertility in South Korea.

Background South Korea has one of the lowest fertility rates in the world, reaching a record low of 0.98 in 2018. Understanding socioeconomic differentials in fertility in South Korea has become an important social and policy issue. Objective This study examines socioeconomic differentials in first and second childbirths among married women using various indicators of socioeconomic status at the individual and household level. Methods Using the Korean Labor and Income Panel Study (1998-2017), discrete-time hazard models are used to evaluate the relationships between multiple indicators of socioeconomic status and the transition to first and second births. Results Higher socioeconomic status (e.g., husband's college education and standard employment, homeownership) is conducive to a transition to parenthood and second births. However, the wife's employment - standard employment in particular - is negatively associated with both first and second childbirth. Among the indicators of socioeconomic resources, stable housing arrangements and the husband's employment security appear to be the most important factors for a married couple's fertility decisions. Conclusions Socioeconomically disadvantaged married couples tend to delay their transition to parenthood. In addition, those with high SES are more likely than their counterparts with low SES to have second births. If these patterns persist, they have important implications for the demographic process and social stratification. Contribution The findings of this study contribute to a comprehensive understanding of socioeconomic differentials in fertility in South Korea and therefore have important policy implications. These findings will also prove useful to other societies with very low fertility rates.
Perspective on theories for reversible potentials for reactions taking place on electrode surfaces

Abstract This article provides a brief overview of three models for calculating activation energies and reversible potentials for oxidation and reduction reactions involving protons at the electrochemical interface and advances the understanding of one of them. Two incorporate the electrode potential in the calculations, the local reaction center (LRC) model where an external electron source or sink is at the chosen potential, and slab-band density functional (DFT) codes which incorporate surface charging to set the potential. The simplest theory comes in two forms: the linear Gibbs energy relationship (LGER) and the computational hydrogen electrode (CHE) model. They have empirical components, inputting experimental data and predicting reversible potentials for surface reactions from calculations of energies for adsorbates at the vacuum interface. LGER uses experimentally measured standard reversible potentials as parameters and CHE employs the work function of the standard hydrogen electrode and the standard value of 0 V for this electrode as parameters. A relationship between LGER and CHE is derived. While LGER predictions depend on two calculated adsorption energies, CHE is demonstrated by means of a Haber cycle to effectively depend on the energy calculated for the reaction in solution as well as the two adsorption energies.