cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5047: Role of estrogen receptors alpha and beta in the balance between proliferation and surveillance

Estrogens have paradoxical effects in both promoting and preventing breast cancer. The proliferative actions of estrogens promote the expansion of both normal mammary epithelium and breast cancer. But estrogen also activates p53-mediated surveillance and apoptotic pathways to eliminate cells with potential oncogenic mutations. This is exemplified by tumor regression in response to high dose estrogen-treatment in postmenopausal breast cancer. Estrogens mediate their effects through the activation of two estrogen receptor subtypes: Estrogen Receptor alpha (ERα)and Estrogen Receptor beta (ERβ). Our objective is to examine the contribution of these receptors in mediating surveillance as opposed to proliferation by comparing selective estrogen receptor agonists with 17β-estradiol (E2) for induction of proliferation and surveillance in three model systems: (1) in vivo mouse model, (2) in vitro MCF7-tet-off-ERβ model, and (3) an ex-vivo human mammary explant model. Selective activation of ERβ with the agonist diarylpropionitrile (DPN) in vivo enhances p53-mediated apoptosis in the mouse mammary epithelium without stimulating proliferation. In addition, radiation-induced apoptosis is significantly reduced in mice lacking ERβ (βERKO). E2 or the ERα selective agonist pyrazole triol (PPT) induced the expression of estrogen response genes including progesterone receptor and amphiregulin in all three models. DPN-mediated activation of ERβ failed to induce the expression of these genes. The ERβ agonist DPN selectively induced the expression of genes that repress proliferation including TGFβ and inhibitors of canonical WNT signaling, WNT5a and AXIN2. DPN was also more potent in stimulating EGR1, a modulator of p53 activity, and CEBPd, a pro-apoptotic gene. Conclusions: The ability of DPN and ERβ to potentiate surveillance pathways while limiting proliferation suggests that ERβ agonists may provide a new approach for chemoprevention of breast cancer. Citation Format: D. Joseph Jerry, Karen A. Dunphy, Amy L. Roberts, Margarita Brown. Role of estrogen receptors alpha and beta in the balance between proliferation and surveillance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5047. doi:10.1158/1538-7445.AM2015-5047
Effect of body composition change on markers of metabolic syndrome in breast cancer survivors on either fat or carbohydrate restricted diets.

A21 Women previously treated for breast cancer are at risk for post-treatment morbidity including obesity, cardiovascular disease, diabetes, and sarcopenia or sarcopenic obesity. The encouragement of weight loss for the management of comorbidities and metabolic disturbance, without consideration of protein content or physical activity, may exacerbate sarcopenia, compromise functional status and lead to increasing risk of future fractures. The purpose of this study is to evaluate the relationship between changes in body composition and metabolic status in the survivor population. >In an ongoing, randomized, weight loss intervention of low fat or low carbohydrate diets in breast cancer survivors (N=37; Age 55.4 ± 9.7 yrs; BMI >25 kg/m2) on adjuvant hormonal therapies, standard anthropometry (height, weight, waist, and hip circumferences) and total and region body fat, lean, and bone mass measures were performed (dual X-ray absorptiometry). Total cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL), insulin, glycosylated hemoglobin, and glucose were also measured by the clinical diagnostic laboratory. >At baseline, we found that 32% of participants had elevated (>3.5) TG/HDL values, a sensitive and specific surrogate measure for insulin resistant, dyslipidemic individuals. In intervention completers thus far (N=14), using the new ATP III criterion, cases of metabolic syndrome were cut by 56% following intervention (metabolic syndrome by ATP III 64% at baseline, 29% at 24weeks) in this survivor group. >At 24 weeks, completers also demonstrated significant improvements in weight and body fat, with suggested loss in lean mass. Although measures of glucose were not altered, fasting insulin and glycosylated hemoglobin were significantly reduced, consistent with improved insulin sensitivity. >Investigations of high protein diets in cancer survivors for the preservation of lean mass during weight loss are limited. This preliminary analysis indicates that markers of metabolic syndrome can be improved by diet in breast cancer survivors, but there is a trend toward loss of lean mass accompanying loss of fat. >Variable Change; p-value >Weight (kg) -8.46 ± 4.08; BMI (kg/m2) -3.05 ± 1.6; %Total Body Fat -4.8 ± 3.0; Trunk Fat (kg) -3.4 ± 1.8; Lean Mass (kg) -0.86 ± 1.6; 0.06 >Fasting Plasma Glucose (mg/dl) -3.00 ± 8.99; 0.18 >2hr-Post-Load Glucose (mg/dl) 8.70 ± 28.39; 0.36 >Fasting Insulin (uU/ml) -3.56 ± 5.83; 0.02 >Glycosylated Hemoglobin (%) -0.17 ± 0.34; 0.05 >Total Cholesterol (mg/dl) -8.61 ± 29.95; 0.24 >Triglycerides (mg/dl) 0.06 ± 77.26; 1.0 >High-density lipoprotein cholesterol (mg/dl) 1.56 ± 9.08; 0.48
Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2

The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of a readily available pool of cis retinoids in the eye. However, the mechanism by which this promiscuous enzyme can gain substrate specificity is unknown. Here, we provide evidence for an allosteric modulation of the enzymatic activity by 11-cis retinoids. This regulation is independent from cellular retinaldehyde-binding protein (CRALBP), the major cis-retinoid binding protein. This positive-feedback regulation leads to decreased esterification rates for 9-cis, 13-cis, or all-trans retinols and thus enables preferential synthesis of 11-cis-retinyl esters. Finally, electron microscopy analyses of the purified enzyme indicate that this allosteric effect does not result from formation of functional oligomers. Altogether, these data provide the experimental basis for understanding regulation of AWAT2 substrate specificity.
CRISPR–Cas systems exploit viral DNA injection to establish and maintain adaptive immunity

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems provide protection against viral and plasmid infection by capturing short DNA sequences from these invaders and integrating them into the CRISPR locus of the prokaryotic host. These sequences, known as spacers, are transcribed into short CRISPR RNA guides that specify the cleavage site of Cas nucleases in the genome of the invader. It is not known when spacer sequences are acquired during viral infection. Here, to investigate this, we tracked spacer acquisition in Staphylococcus aureus cells harbouring a type II CRISPR-Cas9 system after infection with the staphylococcal bacteriophage ϕ12. We found that new spacers were acquired immediately after infection preferentially from the cos site, the viral free DNA end that is first injected into the cell. Analysis of spacer acquisition after infection with mutant phages demonstrated that most spacers are acquired during DNA injection, but not during other stages of the viral cycle that produce free DNA ends, such as DNA replication or packaging. Finally, we showed that spacers acquired from early-injected genomic regions, which direct Cas9 cleavage of the viral DNA immediately after infection, provide better immunity than spacers acquired from late-injected regions. Our results reveal that CRISPR-Cas systems exploit the phage life cycle to generate a pattern of spacer acquisition that ensures a successful CRISPR immune response.
Conscientiousness Moderates the Relationship Between Perceived Stress and Depressive Symptoms Among U.S. Chinese Older Adults

Background The present study examined whether individuals' personality traits, Neuroticism and Conscientiousness, moderated the relationship between perceived stress and depressive symptoms among U.S. Chinese older adults. Methods Data analysis was based on the Population Study of Chinese Elderly in Chicago (PINE). Three thousand one hundred and fifty-nine Chinese adults aged 60 years and older participated in the PINE study. They completed scales that assessed their personality (ie, Neuroticism and Conscientiousness of the NEO Five-Factor Inventory), perceived stress (the Chinese Perceived Stress Scale), and depressive symptoms (the Patient Health Questionnaire). Results Perceived stress was positively related to depressive symptoms among U.S. Chinese older adults. No moderation effects were found for Neuroticism. Conscientiousness significantly moderated the perceived stress-depressive symptom relationship. The positive relationship between perceived stress and depressive symptoms was weaker for people who were higher in Conscientiousness than those who were lower in Conscientiousness. Conclusion Conscientiousness mitigated the stress-depressive symptom relationship among U.S. Chinese older adults. Future research is needed to identify the psychological and sociocultural profiles of individuals who show stress resilience and those who are vulnerable. Social services and psychological interventions are needed to promote health and well-being among U.S. Chinese older adults.
ShortCut: Architectural Support for Fast Object Access in Scripting Languages

The same flexibility that makes dynamic scripting languages appealing to programmers is also the primary cause of their low performance. To access objects of potentially different types, the compiler creates a dispatcher with a series of if statements, each performing a comparison to a type and a jump to a handler. This induces major overhead in instructions executed and branches mispredicted.This paper proposes architectural support to significantly improve the efficiency of accesses to objects. The idea is to modify the instruction that calls the dispatcher so that, under most conditions, it skips most of the branches and instructions needed to reach the correct handler, and sometimes even the execution of the handler itself. Our novel architecture, called ShortCut, performs two levels of optimization. Its Plain design transforms the call to the dispatcher into a call to the correct handler --- bypassing the whole dispatcher execution. Its Aggressive design transforms the call to the dispatcher into a simple load or store --- bypassing the execution of both dispatcher and handler. We implement the ShortCut software in the state-of-the-art Google V8 JIT compiler, and the ShortCut hardware in a simulator. We evaluate ShortCut with the Octane and SunSpider JavaScript application suites. Plain ShortCut reduces the average execution time of the applications by 30% running under the baseline compiler, and by 11% running under the maximum level of compiler optimization. Aggressive ShortCut performs only slightly better.
Development of an In Vitro Exposure System for Live Visualization of the Health Impacts of Oily Marine Aerosol on the Human Respiratory System

Aerosolization of oily water droplets has recently been recognized as a potential respiratory health threat to oil spill cleanup workers, communities near spills, and marine mammals in oil-polluted...
THE FEATURES OF THE USE OF THE REAL AND FICTITIOUS PLACE NAMES IN THE LITERARY TEXTS OF THE LANGUAGES OF DIFFERENT SYSTEMS (AZERBAIJANI AND ENGILISH)

In this article the possibilities of the use of place names in the literary texts of the two languages of different systems are grouped. Here the fact is proved that writers treat individually real place names. In the Azerbaijani and English literary texts real place names are used for two reasons. Firstly, to persuade the reader that the events happening in the literary text are real and secondly, to show that place names are the most effective means of expression of the culture and traditions of the people nowadays. Azerbaijani and English writers also use fictitious place names in their works. As to the usage of fictitious place names, in the Azerbaijani literature J. Mammedguluzadeh and in the English literature T. Hardy are the writers who prefer to use fictitious place names in their works which characterize their style. The relevance of this article is defined by the comparative analysis of the stylistic opportunities of place names on the basis of concrete material of the two languages of different systems (Azerbaijani and English). The aim of the research is to define the role of the real and fictitious place names used within the literary text. The subject of the research is to analyse the function of the place names in the literary texts of the two languages of different systems. The object of the research is the real and fictitious place names used by the Azerbaijani and English writers. In the work the complex technique of investigation is applied and such methods as descriptive, comparative, contextual, stylistic, statistical, etc. are used. The Azerbaijani and English literary texts and also scientific literature on onomastics, stylistics and lexicology were the sources of the research. The results of the work can be applied in reading special courses, holding seminars, writing of research papers and dissertations.
Monte Carlo analysis and Bayesian decision theory for assessing the effects of waste sites on groundwater, II: Applications

Abstract In the preceding paper a sequential Bayesian risk methodology is presented for the assessment of the effects of waste sites on groundwater. Specific details of the Monte Carlo implementation depend on the contaminant transport model employed. In the present paper the modifications used to adapt a deterministic numerical transport model for Monte Carlo analysis in the sequential algorithm are presented, followed by a sensitivity analysis of the resulting stochastic transport model. The sensitivity analysis assesses the impacts of the various sources of uncertainty incorporated, and emphasizes the need to explicitly consider such uncertainty in the process of risk assessment for regulatory decision. Similar modifications to a wide range of contaminant transport models have been incorporated into an advisory computer system for groundwater quality modeling and management.
Material structure-property linkages using three-dimensional convolutional neural networks

Abstract The core materials knowledge needed in the accelerated design, development, and deployment of new and improved materials is most accessible when cast in the form of computationally low cost (reduced-order) and reliable process-structure-property (PSP) linkages. Quantification of the material structure (also referred as microstructure) is the core challenge in this task. Conventionally, microstructure quantification has been addressed using highly simplified measures suggested by the governing physics, with the list of measures often suitably augmented by the intuition of the materials expert. In this paper, we develop an objective (data-driven) approach to efficiently and accurately link a three-dimensional (3-D) microstructure to its effective (homogenized) properties. Our method employs a 3-D convolutional neural network (CNN) to learn the salient features of the material microstructures that lead to good predictive performance for the effective property of interest. We then utilize 3-D CNN learned features as estimators of higher-order spatial correlations, and formulate an integrated framework combining 3-D CNN features with 2-point spatial correlations. In this work, we created an extremely large microstructure-property benchmark dataset of 5900 microstructures, and demonstrated that our CNN based approach not only learns interpretable microstructure features, but also leads to improved accuracy in property predictions for new microstructures, while achieving a dramatic reduction in the computation time.
Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer.

Androgen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer’s disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT. Nine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET (18F-FDGPET) at baseline (before treatment) and again after 9 months of ADT. Whole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem. These findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.
Somatostatin and Depression

Much evidence supports a role for somatostatin as a modulator of central nervous system (CNS) activity and indirectly suggests the relevance of somatostatin to several neuropsychiatric disorders, particularly depression.
Land-Use Changes and CO 2 Emissions Due to US Corn Ethanol Production

There is considerable debate about the global extent of land-use change that would be associated with US production of corn ethanol up to the 15 billion gallons implied by the Energy Independence and Security Act of 2007. This article reviews the processes associated with each of the ways in which such production of corn ethanol could impact land-use changes, and then uses the estimated land-use changes to calculate greenhouse gas (GHG) emissions associated with corn ethanol production. The GHG emissions also are a result of land conversion from forest and pasture to cropland.
The Clinical Definitions of Asthma

It is believed that the term “asthma” was coined by Hippocrates around 450 bc. The term literally means “panting,” from the Greek. Descriptions of the clinical presentation of those affected with asthma appear in medical literature throughout history.
Translational Evaluation of Acid/Base and Electrolyte Alterations in Rodent Model of Focal Ischemia.

Abstract Background and Purpose Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion. Methods Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient middle cerebral artery occlusion models. Results Analysis indicated significant differences in the blood gas and electrolytes between pre- to post-middle cerebral artery occlusion. A decrease in pH and sodium with increases in carbon dioxide, potassium, ionized calcium, and glucose changes were found in both middle cerebral artery occlusion models; while hematocrit and hemoglobin were significant in the transient model. pH and ionized calcium were predictors of infarct volume in the permanent model, as changes in pH and ionized calcium decreased, infarct volume increased. Conclusions There are acute changes in acid/base balance and electrolytes during stroke in transient and permanent rodent models. Additionally, we found pH and ionized calcium changes predicted stroke volume in the permanent middle cerebral artery occlusion model. These preliminary findings are novel, and warrant further exploration in human conditions.
A Logic-based Decomposition Approach for Multi-Period Network Interdiction Models

Abstract This research details the creation of a large-scale optimization approach for solving an application of a multi-period bilevel network interdiction problem (NIP). In this class of multi-period NIP, interdiction activities must be scheduled to minimize the cumulative maximum flow over a finite time horizon. A logic-based decomposition (LBD) approach is proposed that utilizes constraint programming to exploit the scheduling nature of this multi-period NIP. Computational results–comparing solutions obtained using the proposed approach versus traditional mixed-integer programming approach–suggest that the LBD approach is more efficient in finding solutions for medium to large problem instances.
Transitioning from the level surface to stairs in children with and without Down syndrome: Motor strategy and anticipatory locomotor adjustments.

Abstract Background Children with Down syndrome (DS) show underdeveloped motor strategy and anticipatory locomotor adjustments (ALA) before crossing an obstacle. Stairs presents another important setting to study environment navigation and motor adaptation. Inclusion of external ankle load is often used to perturb the stability of a system and observe the emergence of new patterns. Research question How do stair height and external ankle load affect motor strategy and ALA in 5-to-11-year-old children with typical development (TD) and with DS when approaching the stairs? Methods Fourteen children with DS and 14 age- and sex-matched children with TD participated in the study. They walked along a 5-meter walkway and ascended 3-step staircases. There were three staircases (low, moderate, and high heights) and 2 loading conditions (no load and ankle load). A 3D motion capture system was used to collect data. Motor strategy was coded for each trial. Step length, width, time, and velocity, minimum toe clearance, and horizontal toe velocity were calculated for the last four steps before stair ascent. Mixed ANOVAs with repeated measures were conducted for statistical analysis. Results The TD group walked up all the stairs, while the DS group displayed a strategy shift from walking to crawling when the stairs became higher. While the TD group maintained the values of most spatiotemporal variables, the DS group continuously decreased step length and velocity but not step width over the last four approaching steps. Ankle load decreased step length, step velocity, minimum toe clearance, and horizontal toe velocity in the DS group, to a greater extent, than in the TD group. Significance Children with DS show underdeveloped motor strategy and ALA when approaching the stairs, and external ankle load further disrupts these patterns. Stair negotiation appears to be an effective assessment tool for evaluating motor adaptation in children with DS.
The Effect of Work and Family Demands and Work Support on Individual Long-Term Health

Although many scholars believe that work and family demands are negatively related to individual’s long-term physical health only few studies have examined this relationship, mostly using cross-sec...
“Turning a Blind Eye to Ratoon Stunting Disease of Sugarcane in Australia” May Be Putting It Too Strongly Without A Lot More Evidence

A recent Feature article, "Turning a Blind Eye to Ratoon Stunting Disease of Sugarcane in Australia" by Dr. Anthony J. Young, claims "The potential RSD plays a significant, industry-wide role in reduced yields and crop deterioration in Australia has been widely overlooked." As a result, "the industry has exhibited what amounts to an ideological attitude, repeatedly claiming the disease is economically managed." These statements are the basis for the provocative title of the article. Dr. Young presents very elaborately constructed arguments that conclude RSD is likely to be more widespread than realized, is causing significant yield losses and loss of varieties, and is the unrecognized cause of multiple yield decline problems. His overall contention is that the RSD situation has been mismanaged to the detriment of the industry. Allegations such as these should be supported by well documented, direct evidence. Are they supported by solid evidence?
Variational Convexity and the Local Monotonicity of Subgradient Mappings

It is well known that the subgradient mapping associated with a lower semicontinuous function is maximal monotone if and only if the function is convex, but what characterization can be given for the case in which a subgradient mapping is only maximal monotone locally instead of globally? That question is answered here in terms of a condition more subtle than local convexity. Applications are made to the tilt stability of a local minimum and to the local execution of the proximal point algorithm in optimization.
Simulation Activity and Inter-Professional Education in Pre-Licensure Nursing Programs in New Jersey: A 3 Year Trend Analysis

Abstract This three-year descriptive study describes variations of academic requirements, simulation activity, and inter-professional education in diploma, associate, and baccalaureate schools of nursing in New Jersey. The sample represents 32,978 students from 2013–2016. A total of 10,717 qualified student applicants were not offered admission to a NJ nursing program and these reasons included lack of qualified faculty and budgeted faculty positions, limited classroom space, and lack of clinical space.
Designing drought indicators.

AbstractDrought indicators hold great potential to assist water management. However, drought information products are traditionally designed by scientists with little input from the end users. This...
A Stochastic Wireline Communication System

This paper proposes a stochastic wireline communication system. In the proposed stochastic system, the information is encoded in the statistical parameter of noise such as standard deviation, and the noise signal is transmitted on the channel. The receiver estimates the standard deviation of the received noise signal and recovers the information. A stochastic receiver architecture, which can differentiate between the noise signals with two different standard deviations is presented. Using mathematical modeling, this paper demonstrates that the proposed stochastic transceiver has a potential to improve the SNR by more than 3dB over a conventional uncoded deterministic transceiver.
Peaceful Assembly and Association: Donald E. Klingner

By the end of the Middle Ages, Italian city-states reflected two divergent models of urban design. In principalities like San Gemignani, ruling families built tall towers along narrow streets as de...
PEDF-Rpsa-Itga6 signaling regulates cortical neuronal morphogenesis

Neuromorphological defects underlie neurodevelopmental disorders and functional defects. We identified a function for ribosomal protein SA (Rpsa) in regulating neuromorphogenesis using in utero electroporation to knockdown Rpsa, which results in apical dendrite misorientation, fewer/shorter extensions with decreased arborization, and decreased spine density with altered spine morphology. We investigated Rpsa ligand, pigment epithelium-derived factor (PEDF), and interacting partner on the plasma membrane, Integrin subunit α6 (Itga6). Rpsa, PEDF, and Itga6 knockdown cause similar phenotypes, with Rpsa and Itga6 overexpression rescuing morphological defects in PEDF deficient neurons in vivo. Additionally, Itga6 overexpression increases and stabilizes Rpsa expression on the plasma membrane by preventing ubiquitination of Rpsa. GCaMP6s was used to functionally analyze Rpsa knockdown via ex vivo calcium imaging. Rpsa deficient neurons showed less fluctuation in fluorescence intensity, suggesting defective sub-threshold calcium signaling. Our study identifies a role for PEDF-Rpsa-Itga6 signaling in neuromorphogenesis, thus implicating these molecules in the etiology of neurodevelopmental disorders and identifying them as potential therapeutic candidates.
On the almost sure convergence rate for a series expansion of fractional brownian motion

Fractional Brownian motions (fBM) and related processes are widely used in financial modeling to capture the complicated dependence structure of the volatility. In this paper, we analyze an infinite series representation of fBM proposed in (Dzhaparidze and Van Zanten 2004) and establish an almost sure convergence rate of the series representation. The rate is also shown to be optimal. We then demonstrate how the strong convergence rate result can be applied to construct simulation algorithms with path-by-path error guarantees.
Pediatric-Onset Postural Orthostatic Tachycardia Syndrome in a Single Tertiary Care Center.

Aim:We characterize the pediatric postural orthostatic tachycardia syndrome (POTS) population seen at a single tertiary care referral center.Method:Retrospective chart review of all pediatric POTS ...
Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice

Our early studies demonstrated an impressive chemopreventive efficacy of dihydromethysticin (DHM), unique in kava, against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice in which DHM was supplemented in the diet. The current work was carried out to validate the efficacy, optimize the dosing schedule, and further elucidate the mechanisms using oral bolus dosing of DHM. The results demonstrated a dose-dependent chemopreventive efficacy of DHM (orally administered 1 h before each of the two NNK intraperitoneal injections, 1 week apart) against NNK-induced lung adenoma formation. Temporally, DHM at 0.8 mg per dose (∼32 mg per kg body weight) exhibited 100% lung adenoma inhibition when given 3 and 8 h before each NNK injection and attained >93% inhibition when dosed at either 1 or 16 h before each NNK injection. The simultaneous treatment (0 h) or 40 h pretreatment (-40 h) decreased lung adenoma burden by 49.8% and 52.1%, respectively. However, post-NNK administration of DHM (1-8 h after each NNK injection) was ineffective against lung tumor formation. In short-term experiments for mechanistic exploration, DHM treatment reduced the formation of NNK-induced O6-methylguanine (O6-mG, a carcinogenic DNA adduct in A/J mice) in the target lung tissue and increased the urinary excretion of NNK detoxification metabolites as judged by the ratio of urinary NNAL-O-gluc to free NNAL, generally in synchrony with the tumor prevention efficacy outcomes in the dose scheduling time-course experiment. Overall, these results suggest DHM as a potential chemopreventive agent against lung tumorigenesis in smokers, with O6-mG and NNAL detoxification as possible surrogate biomarkers.
Quantifying the Where and How Long of Newborn Care.

* Abbreviation: RU-IP — : resource use inflection point In this issue of Pediatrics , Goldin et al1 report their exploration of a “resource use inflection point” (RU-IP) for infants in 43 NICUs. They define the RU-IP as the day of stay on which daily charges dropped to <10% of the first-day NICU room cost and remained there through just before discharge. Most of their patient sample remained in the hospital even after the RU-IP was reached, and 24% of NICU days occurred after this point. In this study, two important issues are highlighted. First, the authors document substantial variation in the timing of discharge between institutions, as defined by the number of days after reaching this milestone of lower resource use (and, implicitly, lower illness acuity). Assuming that the patient populations in these institutions were similar, such variation would suggest that there is potential to reduce resource use by standardizing discharge criteria and practices, as has been done in many other areas of medicine. Second, researchers in this publication join others who argue that … Address correspondence to John A.F. Zupancic, MD ScD, 330 Brookline Ave, Rose 333, Boston, MA 02215. E-mail: jzupanci{at}bidmc.harvard.edu
Engineering Maize rayado fino virus for virus-induced gene silencing.

Maize rayado fino virus (MRFV) is the type species of the genus Marafivirus in the family Tymoviridae. It infects maize (Zea mays), its natural host, to which it is transmitted by leafhoppers including Dalbulus maidis and Graminella nigrifrons in a persistent-propagative manner. The MRFV monopartite RNA genome encodes a precursor polyprotein that is processed into replication-associated proteins. The genome is encapsidated by two carboxy co-terminal coat proteins, CP1 and CP2. Cloned MRFV can be readily transmitted to maize by vascular puncture inoculation (VPI), and such virus systems that can be used in maize are valuable to examine plant gene function by gene silencing. However, the efficacy of marafiviruses for virus-induced gene silencing (VIGS) has not been investigated to date. To this end, MRFV genomic loci were tested for their potential to host foreign insertions without attenuating virus viability. This was done using infectious MRFV clones engineered to carry maize phytoene desaturase (PDS) gene fragments (ZmPDS) at various genomic regions. Several MRFV-PDS constructs were generated and tested for infectivity and VIGS in maize. This culminated in identification of the helicase/polymerase (HEL/POL) junction as a viable insertion site that preserved virus infectivity, as well as several sites at which sequence insertion caused loss of virus infectivity. Transcripts of viable constructs, carrying PDS inserts in the HEL/POL junction, induced stable local and systemic MRFV symptoms similar to wild-type infections, and triggered PDS VIGS initiating in veins and spreading into both inoculated and noninoculated leaves. These constructs were remarkably stable, retaining inserted sequences for at least four VPI passages while maintaining transmissibility by D. maidis. Our data thus identify the MRFV HEL/POL junction as an insertion site useful for gene silencing in maize.
An experimental and theoretical study of the high temperature reactions of the four butyl radical isomers.

The high temperature gas phase chemistry of the four butyl radical isomers (n-butyl, sec-butyl, iso-butyl, and tert-butyl) was investigated in a combined experimental and theoretical study. Organic nitrites were used as convenient and clean sources of each of the butyl radical isomers. Rate coefficients for dissociation of each nitrite were obtained experimentally and are at, or close to, the high pressure limit. Low pressure experiments were performed in a diaphragmless shock tube with laser schlieren densitometry at post-shock pressures of 65, 130, and 260 Torr and post-shock temperatures of 700–1000 K. Additional experiments were conducted with iso-butyl radicals at 805 K and 8.7 bar to elucidate changes in mechanism at higher pressures. These experiments were performed in a miniature shock tube with synchrotron-based photoionization mass spectrometry. The mass spectra confirmed that scission of the O–NO bond is the primary channel by which the precursors dissociate, but they also provided evidence of a minor channel (<7.7%) through HNO loss and formation of an aldehyde. These high pressure experiments were also used to determine the disproportionation/recombination ratio for iso-butyl radicals as 0.3. Reanalysis of the lower-temperature literature and the present data yielded rate constants for the disproportionation reaction, iso-butyl + iso-butyl = iso-butene + iso-butane. A chemical kinetics model was developed for the reactions of the butyl isomers that included new paths for highly energized adducts. These adducts are formed by the addition of H, CH3 or C2H5 to the butyl radicals. Accompanying theoretical investigations show that chemically activated pathways are competitive with stabilization of the adduct by collision under the conditions of the laser schlieren experiments. These calculations also show that at 10 bar and T < 1000 K stabilization is the only important reaction, but at higher temperatures, even at 10 bar, chemically activated product channels should also be considered. Branching fractions and rate coefficients are presented for these reactions. This study also highlights the importance of the radical structure for determining branching ratios for disproportionation and recombination of alkyl radicals, and these were facilitated by theoretical calculations of recombination rate coefficients for the four butyl radical isomers. The results reveal previously unknown features of butyl radical chemistry under conditions that are relevant to a wide range of applications and reaction mechanisms are presented that incorporate pressure dependent rate coefficients for the key steps.
Radar-Inertial State Estimation and Obstacle Detection for Micro-Aerial Vehicles in Dense Fog

Disaster response and search and rescue missions are among the most difficult missions in which an autonomous robot can be deployed. These require a robot to autonomously navigate chaotic, unstructured indoor and outdoor environments. However popular state estimation and mapping methods using vision and lidar are severely handicapped by fog, smoke, or other airborne particulates; conditions common in disaster scenarios. This work presents radar-based methods for state estimation and mapping that are not affected by smoke and fog. We demonstrate the performance of these methods are comparable to other popular methods in favorable conditions. We also demonstrate visual and lidar-based methods degrade quickly in fog, while our methods do not.
Language Protections for All? Extending and Expanding the Language Protections of the Voting Rights Act

In 2006, Congress renewed Section 203 of the Voting Rights Act, which provides language accommodation in the voting sphere for United States citizens who are Asian American, Native Alaskan, American Indian, or of Spanish-heritage. This chapter in the forthcoming book, DEMOCRACY, PARTICIPATION AND POWER: PERSPECTIVES ON REAUTHORIZATION OF THE VOTING RIGHTS ACT, seeks to build an argument for the extension of Section 203 of the Voting Rights Act to cover and protect additional language minority populations. In doing so, the research focuses particularly on the experiences of Arab American citizens in the United States and builds a case for their inclusion in Section 203.
White Hoarders: A Portrait of Whiteness and Resource Allocation in College Algebra

This study uses Critical Race Theory, Settler Colonialism, and Critical Whiteness Studies to frame how property is recognized only under the auspices of whiteness. In the college algebra classroom,...
Examining the Relationship between the Lethality Assessment/Domestic Violence High-risk Team Monitoring (LAP/DVHRT) Program and Prosecution Outcomes.

Lethality assessment (LAP) and team monitoring of high-risk offenders (DVHRT) are recent U.S. policy innovations designed to identify domestic violence offenders who are at high risk for perpetrati...
A comparative analysis of attribution methods for newly diagnosed cancer patients to hospitals in oncology care.

60Background: Attribution is the term that describes how payers and employers determine which provider is responsible for a member’s care, when prospective patient selection is not available. Sever...
Obesity Is a Risk Factor Associated with H. pylori-negative MALT Lymphoma of Stomach.

OBJECTIVE More than 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are attributed to Helicobacter pylori infections. However, the pathogenesis of H. pylori-negative MALT lymphomas is controversial, and additional etiologies need to be investigated. MATERIALS A retrospective study of gastric MALT lymphoma cases over a 15-year period revealed 56 cases. The H. pylori status, clinical information, and body mass index (BMI) data were collected. The results of the urea breath test, serology, stool antigen, and previous biopsy results were documented. RESULTS The 56 cases had an average height of 166.57 cm (range, 147.3-190.5), weight of 83.98 kg (range 55-153.1), and body mass index (BMI) of 30.34 kg/m2 (range, 17.96-49.77). Twenty-one cases were H. pylori-positive (37.5%), with a mean BMI of 27.36 kg/m2 (range, 17.96-47.25), and BMI>30 kg/m2 in 5 (23.8%) patients. Thirty-five cases were H. pylori-negative, with a mean BMI of 31.90 kg/m2 (range, 18.17-49.77), and 20 (57.1%) having BMI>30 kg/m2. A Fisher's exact test and two-tailed test showed a statistically significant difference between the two groups. CONCLUSION Obesity leads to a baseline state of chronic inflammation and increased production of pro-inflammatory cytokines that can stimulate the lymphocytes, leading to lymphomatous proliferation. Our study suggests a potential correlation between obesity and the risk of development of primary gastric MALT lymphoma.
Expression of Genes Located on the Incompatibility Group FIB Plasmids at Transcription and Protein Levels in Iron-Modified Growth Conditions

Salmonella enterica strains often harbor plasmids representing several incompatibility groups (Inc) including IncFIB, which have been previously associated with carrying antimicrobial resistance and virulence associated genes. To better understand the distribution of virulence factors, we analyzed 37 complete whole genome and plasmid sequences of different S. enterica isolates from multiple serovars that carried IncFIB plasmids. Many of the sequences analyzed carried multiple virulence-associated genes, including those associated with iron acquisition systems; thus we aimed to determine how iron-rich (IR) and various iron-depleted (ID) conditions affected the transcription of iron acquisition and virulence genes including sitA, iutA, iucA, and enolase at different time intervals. Wild type S. enterica strain SE163A and a transconjugant (SE819::IncFIB) were grown in Luria-Bertani (LB) IR and LBID broth for 2, 4, and 18 h. sitA, iutA, and enolase that were grown in LBID conditions were substantially upregulated when compared to LBIR conditions. For both S. enterica strains that were grown at various LBID conditions, 200 µM bipyridyl had the highest transcription for all four genes, followed by the 100 µM concentration. An antibody using a peptide targeting aerobactin receptor gene iutA encoded by IncFIB was generated and used to examine the protein expression in the wild-type, recipient, and transconjugant strain in LB, LBID, and LBIR growth conditions using Western blot analyses. A 70 KDa protein band was detected in the wild-type and transconjugant that carried the IncFIB plasmid, while this band was not detected in the recipient strain that lacked this plasmid. These data provide valuable information to improve our understanding on the iron regulation of virulence associated factors encoded by the IncFIB plasmids.
Quantifying ambient nitrogen uptake and functional relationships of uptake versus concentration in streams: a comparison of stable isotope, pulse, and plateau approaches

Nutrient releases and spiraling metrics are frequently used to quantify the downstream transport of nutrients and to better understand the effects of anthropogenic inputs to downstream waters. Ambient uptake rates in streams can be measured through stable isotope enrichments, while pulse and plateau additions can estimate such rates via extrapolation and modeling techniques, respectively. Data from these releases can be used to estimate ambient uptake rates from nutrient additions and possibly determine the functional relationships between nutrient concentrations and uptake rates. Here, we compared estimated ambient rates calculated from established pulse and plateau approaches, results obtained from new modeling approaches, and rates at ambient concentrations from stable isotope enrichments. Comparative releases of NH4Cl and 15NH4Cl were conducted in four experimental reaches across the grassland Kings Creek and urban Campus Creek, KS. Nutrient uptake was predominantly linear with increasing ammonium. Estimated ambient uptake rates varied among sites, release methods, and data analysis approaches. However, plateau ambient rates from new modeling approaches matched closely with measured ambient rates from isotope enrichments at three sites, suggesting that modeled plateau data may be best for a first look at determining nutrient uptake rates at an individual site. Limitations and benefits of each approach vary; however, baseflow discharge may be a key driver when choosing a method. If possible, multiple methods should be attempted at each location and under each novel set of conditions to determine the best approach prior to designing and implementing a more extensive series of measurements.
The frz Signal Transduction System Controls Multicellular Behavior in Myxococcus xanthus

Myxococcus xanthus is an unusual gram-negative bacterium in that it exhibits a variety of social behaviors and has a complex life cycle. This chapter focuses on the frz signal transduction system, which is a two-component signal transduction system involved in the social behavior of M. xanthus. The authors investigated the isolation of mutants defective in development, and were particularly interested in one group of these mutants, called frizzy or frz, which sporulated normally but formed tangled, frizzy filaments under fruiting conditions instead of the normal fruiting bodies. Based on recombinational and complementation analyses, the frz genes were grouped into at least five complementation groups: frzA, frzB, frzC, frzE, and frzF. The homologies did not prove that the frz genes were chemotaxis genes, because the conserved protein motifs could have evolved new functions. To show spatial chemotactic movement in M. xanthus, it was necessary to set up agar plates, which maintain steep and stable chemical gradients. The authors set up these gradients using petri plates that contain multiple compartments, and found that most frz mutants were no longer able to respond to the spatial or temporal chemical gradients and did not exhibit any chemotactic movements. Western immunoblot and primer extension analysis showed that FrzZ is indeed expressed in vivo during both vegetative growth and development. Genetic, biochemical, behavioral, and molecular biology studies all indicate that the frz genes are the chemotaxis genes of M. xanthus.