cssi/SciSciGPT-SciSciNet huggingface dataset:
Variability in Sleep Patterns: an Emerging Risk Factor for Hypertension.

In this review, we summarize recent epidemiological data (2014–2019) that examine the association of sleep variability with blood pressure (BP), discuss potential underlying mechanisms, and highlight future research directions. Higher standard deviations of sleep duration and sleep-onset timing were not related to BP. However, a higher Sleep Regularity Index score was associated with lower odds of hypertension. Studies on social jetlag, a prevalent form of sleep variability, reported null associations. In contrast, lower interdaily stability in circadian rest-activity rhythms, a measure of invariability in sleep-wake cycles between days and synchronization to light and dark cycles, was associated with higher BP and greater hypertension odds, particularly among non-shift workers. Sleep variability is consistently associated with risk factors for hypertension. Evidence on sleep variability and BP is limited and varies depending on the measure used to characterize day-to-day variability in sleep. Studies that identify and utilize a standard definition of sleep variability, incorporate a 24-h ambulatory BP monitoring, and ensure coinciding timing of sleep and BP measurements are necessary to disentangle these relationships.
Differential DNA accessibility to polymerase enables 30-minute phenotypic β-lactam antibiotic susceptibility testing of carbapenem-resistant Enterobacteriaceae.

The rise in carbapenem-resistant Enterobacteriaceae (CRE) infections has created a global health emergency, underlining the critical need to develop faster diagnostics to treat swiftly and correctly. Although rapid pathogen-identification (ID) tests are being developed, gold-standard antibiotic susceptibility testing (AST) remains unacceptably slow (1–2 d), and innovative approaches for rapid phenotypic ASTs for CREs are urgently needed. Motivated by this need, in this manuscript we tested the hypothesis that upon treatment with β-lactam antibiotics, susceptible Enterobacteriaceae isolates would become sufficiently permeabilized, making some of their DNA accessible to added polymerase and primers. Further, we hypothesized that this accessible DNA would be detectable directly by isothermal amplification methods that do not fully lyse bacterial cells. We build on these results to develop the polymerase-accessibility AST (pol-aAST), a new phenotypic approach for β-lactams, the major antibiotic class for gram-negative infections. We test isolates of the 3 causative pathogens of CRE infections using ceftriaxone (CRO), ertapenem (ETP), and meropenem (MEM) and demonstrate agreement with gold-standard AST. Importantly, pol-aAST correctly categorized resistant isolates that are undetectable by current genotypic methods (negative for β-lactamase genes or lacking predictive genotypes). We also test contrived and clinical urine samples. We show that the pol-aAST can be performed in 30 min sample-to-answer using contrived urine samples and has the potential to be performed directly on clinical urine specimens.
Genome Sequence of a Staphylococcus aureus Strain Isolated from a Dairy Cow That Was Nonresponsive to Antibiotic Treatment.

ABSTRACT Staphylococcus aureus can cause mastitis in dairy cattle. We report the genome sequence of a Staphylococcus aureus strain isolated from a dairy cow with a chronic case of mastitis. The infection with this strain of Staphylococcus aureus was not cleared from the animal with antibiotic treatment.
Discovery and engineering of colchicine alkaloid biosynthesis.

Few complete pathways have been established for the biosynthesis of medicinal compounds from plants. Accordingly, many plant-derived therapeutics are isolated directly from medicinal plants or plant cell culture1. A lead example is colchicine, a US Food and Drug Administration (FDA)-approved treatment for inflammatory disorders that is sourced from Colchicum and Gloriosa species2–5. Here we use a combination of transcriptomics, metabolic logic and pathway reconstitution to elucidate a near-complete biosynthetic pathway to colchicine without prior knowledge of biosynthetic genes, a sequenced genome or genetic tools in the native host. We uncovered eight genes from Gloriosa superba for the biosynthesis of N-formyldemecolcine, a colchicine precursor that contains the characteristic tropolone ring and pharmacophore of colchicine6. Notably, we identified a non-canonical cytochrome P450 that catalyses the remarkable ring expansion reaction that is required to produce the distinct carbon scaffold of colchicine. We further used the newly identified genes to engineer a biosynthetic pathway (comprising 16 enzymes in total) to N-formyldemecolcine in Nicotiana benthamiana starting from the amino acids phenylalanine and tyrosine. This study establishes a metabolic route to tropolone-containing colchicine alkaloids and provides insights into the unique chemistry that plants use to generate complex, bioactive metabolites from simple amino acids. Discovery of a near-complete colchicine biosynthetic pathway enables the engineered production of the tropolone-containing alkaloid N-formyldemecolcine from amino acid precursors in Nicotiana benthamiana.
Electrochemical incineration of benzoquinone in aqueous media using a quaternary metal oxide electrode in the absence of a soluble supporting electrolyte

Electrochemical incineration of p-benzoquinone was evaluated as a model for the mineralization of carbon in toxic aromatic compounds. A Ti or Pt anode was coated with a film of the oxides of Ti, Ru, Sn and Sb. This quaternary metal oxide film was stable; elemental analysis of the electrolysed solution indicated the concentration of these metal ions to be 3μg L−1 or less. The anode showed good reactivity for the electrochemical incineration of benzoquinone. The use of a dissolved salt matrix as the so-called ‘supporting electrolyte’ was eliminated in favor of a solid-state electrolyte sandwiched between the anode and cathode. This substitution permitted the electrolysis solution to be analysed by electrospray mass spectrometry (ESMS); however, as a consequence, electrolysis periods were excessively long. Total organic carbon (TOC) and chemical oxygen demand (COD) decreased to 1–2 mgL−1 after 64h of electrolysis. The solution pH changed from 5 to 4. Phenolic and carboxylic acid intermediate products such as hydroquinone, maleic acid, fumaric acid, succinic acid, malonic acid, acetic acid and formic acids were identified and quantified using solid phase microextraction with gas chromatography with mass spectrometric detection (GCMS) or liquid chromatography (LC) with conductivity detection, absorbance detection, or electrosprary mass spectrometry (ESMS). Less than 1% of the carbon in benzoquinone was converted to acetone and acetaldehyde.
Role for ovarian hormones in purinoceptor-dependent natriuresis.

Premenopausal women have a lower risk of hypertension compared to age-matched men and postmenopausal women. P2Y2 and P2Y4 purinoceptor can be considered potential contributors to hypertension due to their emerging roles in regulating renal tubular Na+ transport. Activation of these receptors inhibits epithelial Na+ channel activity (ENaC) via a phospholipase C (PLC)-dependent pathway resulting in natriuresis. We recently reported that activation of P2Y2 and P2Y4 receptors in the renal medulla by UTP promotes natriuresis in male and ovariectomized (OVX) rats, but not in ovary-intact females. This led us to hypothesize that ovary-intact females have greater basal renal medullary activity of P2 (P2Y2 and P2Y4) receptors regulating Na+ excretion compared to male and OVX rats. To test our hypothesis, we determined (i) the effect of inhibiting medullary P2 receptors by suramin (750 μg/kg/min) on urinary Na+ excretion in anesthetized male, ovary-intact female, and OVX Sprague Dawley rats, (ii) mRNA expression and protein abundance of P2Y2 and P2Y4 receptors, and (iii) mRNA expression of their downstream effectors (PLC-1δ and ENaCα) in renal inner medullary tissues obtained from these three groups. We also subjected cultured mouse inner medullary collecting duct cells (segment 3, mIMCD3) to different concentrations of 17s-estradiol (E2, 0, 10, 100, and 1000 nM) to test whether E2 increases mRNA expression of P2Y2 and P2Y4 receptors. Acute P2 inhibition attenuated urinary Na+ excretion in ovary-intact females, but not in male or OVX rats. We found that P2Y2 and P2Y4 mRNA expression was higher in the inner medulla from females compared to males or OVX. Inner medullary lysates showed that ovary-intact females have higher P2Y2 receptor protein abundance, compared to males; however, OVX did not eliminate this sex difference. We also found that E2 dose-dependently upregulated P2Y2 and P2Y4 mRNA expression in mIMCD3. These data suggest that ovary-intact females have enhanced P2Y2 and P2Y4-dependent regulation of Na+ handling in the renal medulla, compared to male and OVX rats. We speculate that the P2 pathway contributes to facilitated renal Na+ handling in premenopausal females.
Correlation between modified Magee equation-2 and Oncotype-Dx recurrence scores using both traditional and TAILORx cutoffs and the clinical application of the Magee Decision Algorithm: a single institutional review.

Oncotype Dx (ODX) is used to predict recurrence risk for estrogen-positive (ER +), HER2-negative and lymph node negative breast cancer, however, due to the cost its use may be limited in low-resource areas. The aim of this study is to assess the concordance between the modified Magee Equation-2 (MME-2) and ODX recurrence scores (RS). The secondary aim is to apply the Magee Decision Algorithm (MDA) using the MME-2 to determine which patients are unlikely to benefit from ODX testing. All newly diagnosed ER + , HER2 negative, lymph node negative breast cancer patients with available ODX-RS from 2008–2018 were included. The original pathology reports were reviewed and chart review was performed. The MME-2 scores were calculated and correlated with the ODX-RS. The MDA was applied to our cohort to assess which patients would not benefit from ODX testing. A total of 579 patients were included. There was an overall moderate correlation between ODX-RS and MME-2 score (Pearson correlation coefficient = 0.635). The overall concordance between ODX and MME-2 scores was similar when using both the traditional and TAILORx cutoffs (63.3% vs. 63.7%, respectively). Applying the MDA, for patients with MME-2 scores 30, 90% had the expected ODX-RS of > 25. Concordance was highest in the high-risk category using both cutoffs. For patients with MME-2 18–25 and a mitotic score of 1, 88.8% had the expected ODX-RS of > 25. There is a moderate correlation between MME-2 score and ODX-RS. The overall concordance was similar for both traditional and TAILORx cutoffs. The strongest concordance was found in the high-risk category for both cutoffs. The MME-2 can be used to identify patients unlikely to benefit from ODX testing using the MDA.
Noninvasive Cardiac Output Monitoring Using Electrical Cardiometry and Outcomes in Critically Ill Children

Cardiac output (CO) measurement is an important element of hemodynamic assessment in critically ill children and existing methods are difficult and/or inaccurate. There is insufficient literature regarding CO as measured by noninvasive electrical cardiometry (EC) as a predictor of outcomes in critically ill children. We conducted a retrospective chart review in children
Cytosolic Proteostatic Adaptation to Mitochondrial Stress Causes Progressive Muscle Wasting

ABSTRACT Muscle wasting (or atrophy), defined by reduced myofiber size and muscle strength, occurs in primary neuromuscular diseases and during aging. The progressive loss of muscle mass with aging is known as sarcopenia, and affects 35.4% and 75.5% of women and men over 60 years of age, respectively 1. Mitochondrial dysfunction has been proposed to contribute to progressive muscle wasting 2, 3. Interestingly, substantial levels of bioenergetic deficiency and oxidative stress seem to be insufficient by themselves to intrinsically cause muscle wasting during aging4. This raises the possibility that mitochondria may affect muscle mass by additional mechanisms. Here, we show that chronic adaptations to mitochondrial protein overload cause muscle wasting. Protein overloading, together with conditions that directly and indirectly affect the protein import machinery, are known triggers of mitochondrial Precursor Over-accumulation Stress (mPOS), a newly discovered cellular stress mechanism caused by toxic accumulation of precursor proteins in the cytosol 5–7. Our evidence was obtained from transgenic mice that were generated to have a two-fold increase in the nuclear-encoded Ant1 protein that is involved in ATP/ADP exchange on the inner mitochondrial membrane (IMM). These animals progressively lost muscle mass with age, although their lifespan was unaffected. At two years of age, the skeletal muscle of these mice was severely atrophic. The ANT1-transgenic muscles have a drastically remodeled transcriptome that appears trying to counteract mPOS, by repressing protein synthesis and stimulating proteasomal function, autophagy, lysosomal amplification and Gadd45a-signaling. These processes are all known to promote muscle wasting 8, 9. Thus, chronic proteostatic adaptation to mPOS is a robust mechanism of muscle wasting. These findings may help improve the understanding of how mitochondria contribute to muscle wasting during aging. They may also have direct implications for human diseases associated with ANT1 overexpression10–12.
On Multivariate Goodness-of-Fit and Two-Sample Testing

It is shown how classification learning machines can be used to do multivariate goodness-of-fit and two-sample testing.
Adaptive Virtual Reality Exergame for Individualized Rehabilitation for Persons with Spinal Cord Injury

Typical exergames used for rehabilitative therapy can be either too difficult to play or monotonous leading to a lack of adherence. Adapting exergames by tuning various gameplay parameters based on the individual’s physiological ability maintains a constant challenge to improve a participant’s level of engagement and to encourage the physical performance of the user to achieve rehabilitation goals. In this paper we developed a pilot exergame using a commercially available virtual reality (VR) system with varied and customizable gameplay parameters and accessible interface. A baseline task VR tool was previously developed to determine an individual player’s initial 3-D spatial range of motion and areas of comfort. We observed the effects of adjusting gameplay parameters on a participant’s physiological performance by measuring velocity of motions and frequency and effort of targeted movements. We calculated joint torques through inverse kinematics to serve as an analysis tool to quantitatively gauge muscular effort. The system can provide an improved rehabilitation experience for persons with tetraplegia in home settings while allowing oversight by clinical therapists through tracking of physiological performance metrics and movement analysis from mixed reality videos.
Fully Integrated Electronic-Photonic Sensor for Label-Free Refractive Index Sensing in Advanced Zero-Change CMOS-SOI Process

Immediate and widely accessible diagnostics are the key for halting rapidly spreading, and potentially fatal pathogens. A low cost, scalable, real-time biosensing platform unlocks the path towards miniaturized and cost-effective Point of Care (POC) sensors. Here we solve this problem by developing the world’s first fully integrated electronic-photonic, real-time, label-free Refractive Index (RI) sensor, utilizing on-chip electronics and micro-ring resonators (MRRs) in a commercial CMOS 45nm RFSOI platform. RI sensing and real time molecular kinetics are demonstrated for the first time in a monolithic electronic-photonic system-on-chip without requiring bulky optics and off-chip electronic equipment, enabling self-contained real-time POC sensors. The sensitivity performance corresponds to a limit of detection (LoD) of a single 100nm nanoparticle, similar to the size and RI of the SARS-CoV-2 virus.
Of pandemics and zombies: The influence of prior concepts on covid-19 pandemic-related behaviors

We use a concepts and categories research perspective to explore how prior conceptual knowledge influences thinking about a novel disease, namely COVID-19. We collected measures of how similar people thought COVID-19 was to several existing concepts that may have served as other possible comparison points for the pandemic. We also collected participants' self-reported engagement in pandemic-related behaviors. We found that thinking the COVID-19 pandemic was similar to other serious disease outbreaks predicted greater social distancing and mask-wearing, whereas likening COVID-19 to the seasonal flu predicted engaging in significantly fewer of these behaviors. Thinking of COVID-19 as similar to zombie apocalypse scenarios or moments of major societal upheaval predicted stocking-up behaviors, but not disease mitigation behaviors. These early category comparisons influenced behaviors over a six-month span of longitudinal data collection. Our findings suggest that early conceptual comparisons track with emergent disease categories over time and influence the behaviors people engage in related to the disease. Our research illustrates how early concept formation influences behaviors over time, and suggests ways for public health experts to communicate with the public about emergent diseases.
Fighting for a Just Transition

This article posits a Just Transition framework as a useful lens for the next phase of clean energy advocacy in Yucatan, and in Mexico as a whole. This framework is the product of collaboration between a coalition of U.S.-based advocates and frontline community groups who believe that the transition away from fossil fuels requires more than a fuel switch — it requires a complete reimagining of the economy. A Just Transition requires resistance; advocates, academics, and community members must fight to stay informed about proposed and ongoing development. It also requires rethinking and realigning the existing system of power and governance and elevating marginalized voices.
A ratiometric near-infrared fluorescent probe based on a novel reactive cyanine platform for mitochondrial pH detection

A near-infrared reactive cyanine platform (probe A) was prepared by condensation of 9-chloro-1,2,3,4-tetrahydro-10-methyl-acridinium iodide with Fisher's aldehyde. A near-infrared fluorescent probe (probe B) was prepared by modifying a reactive chlorine atom of probe A with tert-butyl(2-aminoethyl)carbamate through a substitution reaction. The deprotection of the Boc group of probe B was achieved under an acidic condition, affording an amine-functionalized cyanine dye (probe C). A near-infrared ratiometric fluorescent probe (probe D) for mitochondrial pH detection was synthesized by conjugating a FRET coumarin donor to a FRET cyanine acceptor (probe C) through an amide bond connection. Probe A shows low fluorescence of 2% due to an electron-withdrawing chlorine atom, while probes B–D display high fluorescence quantum yields of 60%, 32%, and 35% in aqueous solutions containing 10% ethanol, respectively. Probes B–D show strong fluorescence with push–pull molecular structures in neutral and basic pH conditions. However, protonation of the probe's second amine at the 9-position under acidic condition disrupts the push–pull feature of the probes, resulting in fluorescence quenching of the new cyanine fluorophores. The probes can selectively stain mitochondria, while probe D was employed to detect pH changes in HeLa cells and Drosophila melanogaster first-instar larvae.
Visceral fat and arterial stiffness in youth with healthy weight, obesity, and type 2 diabetes.

BACKGROUND AND OBJECTIVES Visceral fat is associated with increased cardiovascular risk in adults, but studies in youth are limited. We assessed associations between visceral fat and arterial stiffness in youth with healthy weight, obesity and type 2 diabetes and determined whether relationships were independent of clinical estimates of body fatness. METHODS This cross-sectional sample included youth ages 10-23 years (67% female, 56% non-black) with healthy weight (body mass index [BMI] = 5th-85th percentile, n = 236), obesity (BMI ≥ 95th percentile, n = 224) and type 2 diabetes (BMI ≥ 95th percentile, n = 145). Visceral fat was assessed via dual-energy X-ray absorptiometry. Carotid-femoral pulse wave velocity (PWV) was assessed via applanation tonometry. Obesity and type 2 diabetes groups were combined for final analyses. Analyses accounted for age, sex, ancestry and mean arterial pressure. RESULTS Visceral fat and PWV were greater in youth with obesity versus healthy weight (p < 0.001). In youth with obesity, but not healthy weight, visceral fat was positively associated with PWV (p < 0.001) and was predictive of PWV beyond BMI and waist circumference. CONCLUSIONS Visceral fat likely contributes to subclinical cardiovascular complications in youth. Since cardiovascular health tracks from adolescence to adulthood, longitudinal studies in youth with obesity are required to define the role of visceral fat in lifelong cardiovascular disease risk.
Private Values and Publicly Traded Securities

Traditional asset pricing models based on fully revealing equilibria have been unable to explain the observed level of the equity premium in the United States without implausibly high risk aversion. I show that when those models are adjusted to reflect the effect of private information about personal preferences, they predict equity premia close to what we have historically observed, regardless of the assumed average level of the risk aversion coefficient, and also regardless of the speed with which prices are assumed to be updated to reflect private information. Based on daily equity return data from the period 1926-2008 and on conservative estimates of the degree of portfolio diversification attainable by households during that period, the model shows that yearly equity premia should have been not less than 5.0%.
The Trapped Mercury Ion Frequency Standard

Singly ionized mercury atoms have a structure similar to neutral alkali atoms. They can be maintained as ions for very long times in an RF quadrupole ion trap. Thus, their ground state hyperfine structure can be used to make a frequency standard using optical pumping techniques similar to the well-known rubidium standard. The mass 199 isotope of mercury has an ionic hyperfine structure of 40.5 GHz. In a trap system a linewidth of 10 Hz has been measured. An expression is presented for the short-term stability of a proposed mercury standard as set by the achieved signal to noise ratio. There is prospect of further improvement. Long-term stability is affected by second order doppler effect, and by pressure, light, and Stark shifts. However, these appear either sufficiently small or sufficiently controlable that the proposed mercury ion standard would be competitive with existing standards.
Heat transfer predictions of the Poisson noise model for nonlinear devices

Previous work has shown that a Poisson model for noise in nonlinear devices satisfied several thermodynamic tests when,connected to fairly general circuits containing lossless elements and possibly Nyquist-Johnson noisy resistors. This paper adds yet another test: does the model predict heat transfer between nonlinear devices, or between a nonlinear device and a linear resistor? In short, to extend the classic Brillouin Paradox, can a diode rectify another diode's thermal noise?.
8-classtype tallying device and counter.

An electronic device using transistor-transistor-logic integrated circuits as primary building blocks was designed and constructed to accumulate counts for eight classtypes. Selection of the classtypes is provided for by three encoders, X, Y, and Z. Using these encoders allows selection of memory counters for accumulations of 0 to 99 counts per classtype. Making X, Y, and Z the input equivalents of three genes permitted direct tallying and accumulation of totals of individual phenotypes for recombinant progeny containing three scorable genes. The use of the device as a simple one-of-four colony counter is described. Use of the instrument for obtaining counts of multiply characterized colonies was possible. In all tested instances, tedium and the labor of obtaining differential counts was reduced by more than fourfold with a great increase in accuracy of count accumulations. Complete information is provided for the fabrication of the instrument for use in individual laboratories. Images
Lipid components that reduce protein solubility of soy protein isolates

A lipid fraction from a commercial soy protein isolate (SPI), previously found to be detrimental to SPI solubility, was analyzed by size-exclusion liquid chromatography, by high-performance liquid chromatography (HPLC), and for chemical composition. The molecular weight of most of this material was greater than 1,100 daltons. This lipid fraction was water-soluble yet required a strong nonpolar solvent mixture to elute it from a C18 HPLC column. The lipid material was alkaline (pH 8.7) and composed of 3.0% nitrogen, 1.6% phosphorus, 17.5% nonvolatile crude fatty acids primarily hydroxylated), 10.4% long-chain bases, 9.9% hexuronic acid, 3.2% hexosamine, and 6.6% total sugar. The molecular weight, chemical composition, and physical characteristics (solubility characteristics, surfactant characteristics, and appearance) of this material were all similar to those reported for phytoglycolipid.
Dendritic cell-based immunotherapy for malignant gliomas.

Despite dramatic advances in surgical techniques, imaging and adjuvant radiotherapy or chemotherapy, the prognosis for patients with malignant glial tumors remains dismal. Based on the current knowledge regarding immune responses in the healthy CNS and glioma-bearing hosts, this review discusses dendritic cell-based immunotherapeutic approaches for malignant gliomas and the relevance of recent clinical trials and their outcomes. It is now recognized that the CNS is not an immunologically tolerated site and clearance of arising glioma cells is a routine physiologic function of the normal, noncompromised immune system. To escape from immune surveillance, however, clinically apparent gliomas develop complex mechanisms that suppress tumoricidal immune responses. Although the use of dendritic cells for the treatment of glioma patients may be the most appropriate approach, an effective treatment paradigm for these tumors may eventually require the use of several types of treatment. Additionally, given the heter...
Evaluation of Bedtime Basics for Babies: A National Crib Distribution Program to Reduce the Risk of Sleep-Related Sudden Infant Deaths

Rates of sleep-related infant deaths have remained stagnant in recent years. Although most parents are aware of safe sleep recommendations, barriers to adherence, including lack of access to a safe crib, remain. The objective of this study was to describe parental knowledge and practices regarding infant sleep position, bedsharing, pacifier use, and feeding practices before and after receipt of a free crib and safe sleep education. Bedtime Basics for Babies (BBB) enrolled high-risk families in Washington, Indiana, and Washington, DC and provided them with cribs and safe sleep education. Parents completed surveys before (“prenatal” and “postnatal”) and 1–3 months after crib receipt (“follow-up”). Descriptive and bivariate analyses were completed. 3,303 prenatal, 1,483 postnatal, and 1,729 follow-up surveys were collected. Parental knowledge of recommended infant sleep position improved from 76 % (prenatal) and 77 % (postnatal) to 94 % after crib receipt (p < 0.001). Intended use of supine positioning increased from 84 % (prenatal) and 80 % (postnatal) to 87 % after the intervention (p < 0.001). Although only 8 % of parents intended to bedshare when asked prenatally, 38 % of parents receiving the crib after the infant’s birth reported that they had bedshared the night before. This decreased to 16 % after the intervention. Ninety percent reported that the baby slept in a crib after the intervention, compared with 51 % postnatally (p < 0.01). BBB was successful in changing knowledge and practices in the majority of high-risk participants with regards to placing the infant supine in a crib for sleep. Crib distribution and safe sleep education positively influence knowledge and practices about safe sleep.
Polyoma disease and tumors in mice: the distribution of viral antigen detected by immunofluorescence.

Abstract Polyoma disease and polyoma-induced tumors in AK/Z mice were studied by means of fluorescein-labeled mouse antibody. Mice with acute fatal polyoma disease showed polyoma viral antigen in the kidney in focal areas consisting of renal tubule cells undergoing nuclear swelling and lysis. The antigen was also noted in thyroid and salivary glands. In tumor-bearing mice, polyoma viral antigen was found in malignant cells showing nonspecific degenerative changes similar to those seen in nonmalignant cells being destroyed by polyoma virus. These cells were usually isolated, but sometimes in groups. Tumor-bearing mice showed persistent virus-productive lesions in kidney, thyroid, and salivary glands. The viral antigen in both malignant and nonmalignant cells was primarily found in the nucleus, but it was also found in the cytoplasm of damaged cells. The number of cells showing viral antigen in any given tumor was not related to the type of tumor.
Exploring emotions and the economy: new contributions from sociological theory

In fall of 2008, global economic depression seemed a viable future possibility. As the U.S. stock market went into in free fall and major financial institutions collapsed on an almost daily basis, a colleague casually mentioned the volatility of the "fear index" as a measure of financial instability. My initial reaction was that my colleague
Differential Glucocorticoid Receptor-mediated Transcription Mechanisms

Nuclear receptors such as the glucocorticoid receptor (GR) are ligand-dependent transcription factors that mediate transcription of target genes by recruiting factors that modulate chromatin structure. In this study, curcumin, a compound known to inhibit GR-mediated transcription, was used to examine the different mechanisms by which GR regulates transcription. The mechanisms of transcription regulation of metallothioneine-2A (MT2A) and solute carrier family 19 member 2 (SLC19A2), two GR target genes where the hormone-dependent gene activation is inhibited or unaffected by curcumin treatment, respectively, were analyzed by chromatin immunoprecipitation and RT-PCR experiments. The data suggest that the loss of hormone-dependent MT2A gene expression is due to the inhibition of continued transcription activity after initial assembly of the transcription machinery. In contrast, the hormone-dependent SLC19A2 gene expression is maintained because the continued transcription output after assembly of transcription machinery is unaffected by curcumin. These results suggest that the two GR target genes use alternate mechanisms to regulate expression levels at the level of continued transcription output after transcription machinery assembly.
Identification of Innate Immune Response Endotypes in Asthma: Implications for Personalized Medicine

Asthma is an idiopathic disease characterized by episodic inflammation and reversible airway obstruction triggered by exposure to environmental agents. Because this disease is heterogeneous in onset, exacerbations, inflammatory states, and response to therapy, there is intense interest in developing personalized approaches to its management. Of focus in this review, the recognition that a component of the pathophysiology of asthma is mediated by inflammation has implications for understanding its etiology and individualizing its therapy. Despite understanding how Th2 polarization mediates asthma exacerbations by aeroallergen exposure, we do not yet fully understand how RNA virus infections produce asthmatic exacerbations. This review will summarize the explosion of information that has revealed how patterns produced by RNA virus infection trigger the innate immune response (IIR) in sentinel airway cells. When the IIR is triggered, these cells elaborate inflammatory cytokines and protective mucosal interferons whose actions activate long-lived adaptive immunity and limit organismal replication. Recent work has shown the multifaceted way that dysregulation of the IIR is linked to viral-induced exacerbation, steroid insensitivity, and T helper polarization of adaptive immunity. New developments in quantitative proteomics now enable accurate identification of subgroups of individuals that demonstrate activation of IIR (“innate endotype”). Potential applications to clinical research are proposed. Together, these developments open realistic prospects for how identification of the IIR endotype may inform asthma therapy in the future.
Differential effect of Ca+2 on the translation of yeast mitochondrial and some viral RNA'S in an E.coli cell-free system.

Abstract Addition of 6mM CaCl2 to an E. coli cell-free system resulted in a several-fold enhancement of yeast mt RNA translation and in a severe inhibition of protein synthesis directed by MS2, Qβ and T5 RNA's. CaCl2 did not alter the Mg+2 optimum or the time-course of protein synthesis and had no apparent effect on RNA degradation. Formaldehyde treatment of MS2 RNA markedly diminished the CaCl2-mediated inhibition of its translation. Addition of equimolar amounts of EGTA, together with CaCl2, abolished the effect of the latter on cell-free protein synthesis. FMet tRNA binding to ribosomes was enhanced by CaCl2 in the presence of mt RNA, inhibited in the presence of MS2 RNA, and unaffected in the presence of formaldehyde-treated MS2 RNA. Maximal effect on initiation complex formation was observed with 0.1 mM CaCl2.
Factors influencing nest survival and productivity of Red-throated Loons (Gavia stellata) in Alaska

ABSTRACT Red-throated Loon (Gavia stellata) numbers in Alaska have fluctuated dramatically over the past 3 decades; however, the demographic processes contributing to these population dynamics are poorly understood. To examine spatial and temporal variation in productivity, we estimated breeding parameters at 5 sites in Alaska: at Cape Espenberg and the Copper River Delta we estimated nest survival, and at 3 sites within the Yukon-Kuskokwim Delta we estimated nest survival and productivity. Nest survival varied broadly among sites and years; annual estimates (lower, upper 95% confidence interval) ranged from 0.09 (0.03, 0.29) at Cape Espenberg in 2001 to 0.93 (0.76, 0.99) at the Copper River Delta in 2002. Annual variation among sites was not concordant, suggesting that site-scale factors had a strong influence on nest survival. Models of nest survival indicated that visits to monitor nests had a negative effect on nest daily survival probability, which if not accounted for biased nest survival strongly d...
Line Formation in Collapsing Cloud Cores with Rotation and Applications to B335 and IRAS 16293-2422

We present radiative transfer models of collapsing clouds with rotation and apply them to B335 and IRAS 16293-2422, the two best candidates of protostellar collapse known to date. By including rotation in the manner of Tereby, Shu, & Cassen (1984), we can reproduce the profiles of several molecular lines not only toward the center position, but also toward a grid of positions near the center. We find that the model of B335 by Zhou et al. (1993) is not affected significantly by the presence of rotation. By including rotation, we can reproduce the observations of IRAS 16293-2422 by Menden et al. (1987); hence, we support the infall interpretations of spectral lines from IRAS 16293-2422 proposed by Walker et al. (1986). We also observed the large-scale rotation of IRAS 16293-2422 in the C(18)O J = 2 approaches 1 line. The observed rotation rate is a factor of 6 smaller than that required to explain the small-scale CS data of Menden et al. (1987). This probably means the precollapse cloud has differential rotation, possibly due to more efficient magnetic braking on large scales.
Hemlock woolly adelgid (Homoptera: Adelgidae) dispersion and the failure of binomial sampling to estimate population density

Data collected in 1994 and 1995 from eastern hemlock stands in Pennsylvania and Virginia were used to evaluate the binomial sampling method for hemlock woolly adelgid. An empirical distribution model and a model based on the negative binomial distribution were used to describe the relationship between mean hemlock woolly adelgid density ( x ) and the proportion of samples with at least T hemlock woolly adelgid ( PT ). There were significant differences in the x versus PT relationship between locations and hemlock woolly adelgid generations regardless of the value of T (1–10) or model used. The inconsistency of the relationship may be a result of the respective phenologies of hemlock woolly adelgid and eastern hemlock, and of the effect that continued hemlock woolly adelgid feeding has on the production of new foliage. Binomial sampling procedures have been successfully developed for many pests of agricultural crops. The technique may not be suitable for long-lived hosts where pest attack significantly alters the food resource.
Input Demands and Inefficiency in U.S. Agriculture

Markov Chain Monte Carlo (MCMC) methods are used to estimate a seemingly unrelated regression (SUR) system of input demand functions for U.S. agriculture. Our demand functions have flexible forms and allow for nonrandom technical inefficiency. Concavity constraints are imposed at individual data points, and the distributions of measures of relative technical efficiency are constrained to the unit interval. Results are evaluated in terms of characteristics of the posterior distributions of parameters, measures of relative technical efficiency, and other nonlinear functions of the parameters.
Impact of process variation in inductive integrated voltage regulator on delay and power of digital circuits

This paper analyzes the effect of variations in the parameters of an Integrated Voltage Regulator (IVR) and its impact on the power/performance of a system of IVR driven digital logic circuit. The coupled analysis of IVR and digital logic considering variations in the integrated passives, power train FETs and controller transistors shows, compared to an off-chip VR, variations in IVR induce much larger shifts in the operating frequency of the logic and total system power. Variations in the output filter passives cause most prominent variations in the system power and performance, particularly pronounced at low voltage operation of the core. We also show that the mean performance of the system can be traded-off to reduce the variability by modifying IVR parameters, such as controller zeroes or output capacitors.
Increasing scientific power with statistical power.

A survey of basic ideas in statistical power analysis demonstrates the advantages and ease of using power analysis throughout the design, analysis, and interpretation of research. The power of a statistical test is the probability of rejecting the null hypothesis of the test. The traditional approach to power involves computation of only a single power value. The more general power curve allows examining the range of power determinants, which are sample size, population difference, and error variance, in traditional ANOVA. Power analysis can be useful not only in study planning, but also in the evaluation of existing research. An important application is in concluding that no scientifically important treatment difference exists. Choosing an appropriate power depends on: a) opportunity costs, b) ethical trade-offs, c) the size of effect considered important, d) the uncertainty of parameter estimates, and e) the analyst's preferences. Although precise rules seem inappropriate, several guidelines are defensible. First, the sensitivity of the power curve to particular characteristics of the study, such as the error variance, should be examined in any power analysis. Second, just as a small type I error rate should be demonstrated in order to declare a difference nonzero, a small type II error should be demonstrated in order to declare a difference zero. Third, when ethical and opportunity costs do not preclude it, power should be at least .84, and preferably greater than .90.
Investment in Testes and the Cost of Making Long Sperm in Drosophila

Relationships among body mass, testis mass, sperm length, and the number of sperm produced were examined among 11 Drosophila species, after controlling for phylogenetic ef- fects. This is the first study to examine many of these relationships comparatively in an inverte- brate taxon; patterns observed among these variables were fundamentally different from those consistently reported in studies of vertebrates. In regression analyses, testis mass increased with body mass with an exponent greater than one, which indicates that males of larger-bodied Drosophila species make a proportionately greater energetic investment in testes than do males of smaller-bodied species. The positive allometry of testis mass is hypothesized to be a combined consequence of the unusual positive relationship between body mass and sperm length and the positive relationship between sperm length and testis mass. Interspecific variation in testis mass was found to be a function of variation in sperm length rather than variation in the number of sperm produced. Significant trade-offs were identified between sperm length and the number of sperm produced and transferred per copulation. Results are discussed in terms of the costs of producing longer sperm, the correlated evolution of sperm length and body size, the relation- ship between breeding system and sperm production patterns, and the nature of differences between vertebrates and invertebrates in sperm production and the size of testes.
Finite Element Modeling of Edge Trimming Fiber Reinforced Plastics

A finite element model was developed to simulate chip formation in the edge trimming of unidirectional Fiber Reinforced Plastics (FRPs) with orthogonal cutting tools. Fiber orientations (θ) within the range of 0 deg≤θ≤90 deg were considered and the cutting tool was modeled as both a rigid and deformable body in independent simulations. The principal and thrust force history resulting from numerical simulations for orthogonal cutting were compared to those obtained from edge trimming of unidirectional Graphite/Epoxy (Gr/Ep) using polycrystalline diamond tools. It was found that principal cutting forces obtained from the finite element model with both rigid and deformable body tools compared well with experimental results. Although the cutting forces increased with increasing fiber orientation, the tool rake angle had limited influence on cutting forces for all orientations other than 0=0 deg and 90 deg. However, the tool geometry did affect the degree of subsurface damage resulting from interlaminar shear failure as well as the cutting tool stress distribution. The finite element model for chip formation provides a means for optimizing tool geometry over the total range in fiber orientations in terms of the cutting forces, degree of subsurface trimming damage, and the cutting tool stresses.
Trabecular meshwork recovery after phagocytic challenge.

The short and long term response of the trabecular meshwork to a phagocytic challenge and the response of the meshwork to different types of foreign particles was studied by injecting one eye of 25 adult cats with a phagocytic agent (zymosan, blood, or latex microspheres) while the fellow eye received a control solution. Eyes were examined histologically at various intervals from one day to five months after infusion. Active trabecular cell phagocytosis and changes in cell shape were found with all agents. The extent of these changes varied with the agent used.Zymosan caused marked changes and inflammation, with numerous macrophages found throughout the meshwork. Trabecular cell migration and cell loss occurred, although it was often difficult to distinguish macrophages from rounded trabecular cells. The meshwork eventually recovered from this inflammatory insult, as trabecular lamellae became less edematous and once again acquired a lining of trabecular cells. Blood and latex microspheres caused less dis...
Incorporating functional annotation information in prioritizing disease associated SNPs from genome wide association studies

With recent advances in genotyping and sequencing technologies, many disease susceptibility loci have been identified. However, much of the genetic heritability remains unexplained and the replication rate between independent studies is still low. Meanwhile, there have been increasing efforts on functional annotations of the entire human genome, such as the Encyclopedia of DNA Elements (ENCODE) project and other similar projects. It has been shown that incorporating these functional annotations to prioritize genome wide association signals may help identify true association signals. However, to our knowledge, the extent of the improvement when functional annotation data are considered has not been studied in the literature. In this article, we propose a statistical framework to estimate the improvement in replication rate with annotation data, and apply it to Crohn’s disease and DNase I hypersensitive sites. The results show that with cell line specific functional annotations, the expected replication rate is improved, but only at modest level.
Characterization and clinical behavior of Crohn's disease initially presenting predominantly as colitis.

PURPOSE: We studied patients with Crohn’s disease affecting the colon to characterize disease behavior and to determine whether such patients might be candidates for sphincter-sparing surgery. METHODS: Ninety-two consecutive patients with Crohn’s colitis were studied prospectively. Mean follow-up after diagnosis was 82 (range, 6–291) months. Parameters that were evaluated included previous surgery for Crohn’s disease, granulomatous vs. nongranulomatous disease, extent of colonic involvement, and presence or absence of extracolonic disease. The clinical course of the disease and postoperative outcome were evaluated. The outcome of Crohn’s colitis patients who underwent ileal pouch-anal anastomosis for presumed ulcerative colitis was also evaluated. RESULTS: There were 39 patients with granulomatous colitis and 53 patients without granulomas. There was no statistical difference in the age of diagnosis or presence of small-bowel (23 vs. 27 percent), ileocolic (34 vs. 30 percent), or perineal (36 vs. 22 percent) disease in these patients. At initial presentation, 88 percent of patients with pancolitis had colitis alone without other sites of intestinal disease compared with only 37 percent of patients with segmental colitis (P < 0.001). Kaplan-Meier analysis showed that patients with granulomas and patients with segmental colitis at presentation have a significantly higher recurrence when compared with patients without granulomas and patients with pancolitis (P < 0.03). Thirteen patients without granulomatous disease and eight with granuloma underwent ileal pouch-anal anastomosis. Seven patients (3 with granuloma, 4 without granuloma) had a recurrence of Crohn’s disease in the ileal pouch; 2 required pouch removal and permanent diversion for fistulizing disease in the ileal pouch and 5 were successfully treated conservatively without surgery. CONCLUSION: The presence of granulomas and segmental involvement of the colon in patients with Crohn’s colitis may reflect a more virulent clinical course. Ileal pouch-anal anastomosis may be considered as an option in select patients with Crohn’s colitis without small-bowel or perianal disease. Based on our data, patients with nongranulomatous pancolitis may be better candidates for sphincter-sparing surgery.
On the convergence of rational functions orthogonal on the unit circle

Rational functions orthogonal on the unit circle with prescribed poles are studied. We establish some convergence theorems for the orthogonal rational functions. We generalize some of the results for Szego polynomials to rational orthogonal functions.