cssi/SciSciGPT-SciSciNet huggingface dataset:
Exposure-disease continuum for 2-chloro-2'-deoxyadenosine, a prototype ocular teratogen. 1. Dose-response analysis.

Background Treatment of pregnant mice with 2-chloro-2′-deoxyadenosine (2CdA) on day 8 of gestation induces microphthalmia through a mechanism coupled to the p53 tumor suppressor gene. The present study defines 2CdA dosimetry with respect to exposure (pharmacokinetics), p53 protein induction, and disease (microphthalmia). Methods Pregnant CD-1 mice dosed with 0.5–10.0 mg/kg 2CdA on day 8 provided fetuses for teratological evaluation; 2CdA was measured by HPLC in the antimesometrium through 180 min postexposure, and p53 was assessed with immunostaining of the embryo through 270 min. 5′-/3′-RACE was used to sequence the candidate gene for 2CdA bioactivation from target cells. Results Microphthalmia appeared first in the dose-response curve. The highest 2CdA dose having no observable adverse effect (NOAEL) was 1.5 mg/kg; the benchmark dose that produced an extra 5% risk of microphthalmia (BMD5) was 2.5 mg/kg, and the lower confidence limit (BMDL) was 2.0 mg/kg. Pharmacokinetic parameters for doses encompassing the threshold (1.5–2.5 mg/kg) were modeled at 1.0–1.8 μM (Cmax) and 30–80 μM-min (AUC). The p53 response was not detected below the BMDL; however, a low-grade response appeared 4.5 hr after a teratogenic dose (5.0 mg/kg), and high-grade induction followed an embryolethal dose (10.0 mg/kg). RACE identified a novel splice variant of mitochondrial deoxyguanosine kinase, dGK-3, as the likely candidate for 2CdA bioactivation in the embryo. Conclusions Microphthalmia represented the critical effect malformation of 2CdA. The findings suggest a mitochondrial mechanism for 2CdA bioactivation, leading to an embryonic p53 response only after 2CdA elimination and implying pharmacodynamic coupling to the exposure–disease continuum. Teratology 64:154–169, 2001. Published 2001 Wiley-Liss, Inc.
Giga-pixel nanoimaging using computational on-chip microscopy

Optical imaging of sub-micron features requires high resolution and contrast. Using no imaging lenses, we achieve a numerical aperture of 0.92 over a large field-of-view (FOV) of e.g., >20 mm2. In parallel, we significantly enhance image contrast using self-assembled nanolenses, which form catenoids at the nanoscale, enabling sub-100-nm particle and virus detection over a wide FOV.
Anatomic and physiologic age changes in the kidney

Abstract Cross-sectional studies of renal function in man indicate there is a progressive decline with age after the age of 40 years. The blood vessels, glomeruli, tubules and interstitium are all potential sites of primary involvement in the aging process as well as for renal disease. Regardless of the anatomic structure initially affected, most chronic renal conditions evolve with destruction of the entire nephron. Whether the observed decrease in renal function associated with aging is the result of intervening pathologic processes, e.g. ischemia (vascular obliteration) or infection, or is the result of a more insidious involutional process, it has generated much discussion but few answers. The purpose of this report is to review the descriptive studies documenting the changes in renal morphology and physiology with age and to focus on what is known about the mechanisms involved in these losses of renal substance and function.
Fat paradox in liver disease.

Alcoholic liver disease (ALD) is characterized by accumulation of neutral lipids in hepatocytes leading to micro and macro-vesicular steatosis and balloon cell degeneration. Hypercaloric alimentation and resultant obesity also cause similar changes as evident in non-alcoholic fatty liver disease (NAFLD). Thus, accumulation of lipids in hepatocytes is a pathologic hallmark of ALD and NAFLD. In contrast, quiescent hepatic stellate cells (HSC) are characterized by the intracellular content of not only vitamin A but also triglycerides, and HSC activation is associated with depletion of these lipids. In fact, our recent work demonstrates that adipogenic/lipogenic transcriptional regulation rendered by PPARγ, LXRα, and SREBP-1c is essential for the maintenance of the fat-storing, quiescence phenotype of HSC. Expression of these adipogenic transcription factors is lost in activated HSC and the treatment of the cells with the adipocyte differentiation cocktail or ectopic expression of PPARγ or SREBP-1c causes a reversal of activated cells to the quiescent phenotype. In steatotic livers from ALD and NAFLD mouse models, the expression of these adipogenic transcription factors is induced while the normal control livers lack such expression. Thus, adipogenic regulation is essential for HSC quiescence while it makes hepatocytes steatotic. Interestingly, under the adipogenic conditions of ALD and NAFLD, HSC are still activated to cause fibrosis. This fat paradox in hepatocytes and HSC highlights contrasted significance of fat in these two cell types that depend on each other for their homeostatic control. It further suggests, activated HSC in steatotic livers may have defective insulin signaling or lipogenic regulation.
Persistent respiratory effects in survivors of the Bhopal disaster.

OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the development of persistent obstructive airways disease. DESIGN: Cross sectional survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES: Self reported respiratory symptoms; indices of lung function measured by simple spirometry and adjusted for age, sex, and height according to Indian derived regression equations. RESULTS: Respiratory symptoms were significantly more common and lung function (percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and FEV1/FEV ratio) was reduced among those reporting exposure to the gas leak. The frequency of symptoms fell as exposure decreased (as estimated by distance lived from the plant), and lung function measurements displayed similar trends. These findings were not wholly accounted for by confounding by smoking or literacy, a measure of socioeconomic status. Lung function measurements were consistently lower in those reporting symptoms. CONCLUSION: Our results suggest that persistent small airways obstruction among survivors of the 1984 disaster may be attributed to gas exposure.
Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity

Amino acid sequence homology was found between viral and host encephalitogenic protein. Immune responses were then generated in rabbits by using the viral peptide that cross-reacts with the self protein. Mononuclear cell infiltration was observed in the central nervous systems of animals immunized with the viral peptide. Myelin basic protein (MBP) is a host protein whose encephalitogenic site of ten amino acids induces experimental allergic encephalomyelitis. By computer analysis, hepatitis B virus polymerase (HBVP) was found to share six consecutive amino acids with the encephalitogenic site of rabbit MBP. Rabbits given injections of a selected eight- or ten-amino acid peptide from HBVP made antibody that reacted with the predetermined sequences of HBVP and also with native MBP. Peripheral blood mononuclear cells from the immunized rabbits proliferated when incubated with either MBP or HBVP. Central nervous system tissue taken from these rabbits had a histologic picture reminiscent of experimental allergic encephalomyelitis. Thus, viral infection may trigger the production of antibodies and mononuclear cells that cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoallergic event can take place in the absence of the infectious virus that initiated the immune response.
Dielectric loss at high frequency

In the application of dielectric heating to various industrial processes, alternating frequencies between 1 and 30 megacycles, and rates of temperature rise of 50 degrees Fahrenheit and upward, are common. The measurement of the dielectric properties of a material under such varying conditions presents a problem which may be solved by a calorimetric substitution method.
Afferent and efferent connections of the medial, inferior and lateral vestibular nuclei in the cat and monkey

Attempts were made to determine the afferent and efferent connections of the medial (MVN), inferior (IVN) and lateral (LVN) vestibular nuclei (VN) in the cat and monkey using retrograde and anterograde axoplasmic transport technics. Injections of HRP and [3H]amino acids were made selectively into MVN, IVN and LVN and into: (1) MVN and IVN, (2) LVN and IVN and (3) all 4 VN. Contralateral afferents to MVN arise from (1) the nuclei prepositus (NPP) and intercalatus (NIC), (2) all parts of MVN and cell group 'y' and (3) parts of the superior vestibular nucleus (SVN), IVN and the fastigial nucleus (FN). Ipsilateral projections to MVN arise from: (1) a central band of the flocculus and the nodulus and uvula, (2) the interstitial nucleus of Cajal (INC), and (3) visceral nuclei of the oculomotor nuclear complex (OMC). Efferent projections of MVN are to: (1) the ipsilateral supraspinal nucleus (SSN), and (2) the contralateral central cervical nucleus (CCN), MVN, SVN, cell group 'y', the rostroventral region of LVN, the trochlear nucleus (TN) and the INC. Projections to the abducens nuclei (AN) and the OMC are bilateral. Some ascending fibers in the cat cross within the OMC. In the monkey fibers from MVN end in a central band of the ipsilateral flocculus. Afferents to IVN arise ipsilaterally from SVN, the nodulus, the uvula and the anterior lobe vermis. Contralateral afferents arise from: (1) parts of CCN, MVN, SVN, IVN and cell group 'y' and (2) the central third of the FN. IVN receives bilateral projections from the perihypoglossal nuclei (PH) and the visceral nuclei of the OMC. Efferents from IVN project: (1) ipsilaterally to nucleus beta of the inferior olive, (2) contralaterally to parts of MVN, SVN and cell group 'y' and (3) bilaterally to the paramedian reticular nuclei. No commissural fibers interconnect cell groups 'f' and 'x'. Ascending fibers from IVN terminate contralaterally in the TN and the OMC. In the monkey fibers from IVN terminate in the ipsilateral nodulus, uvula and anterior lobe vermis; no fibers project to FN in either the cat or the monkey. Afferents to the LVN arise primarily from the ipsilateral anterior lobe vermis and bilaterally from rostral parts of the FN. No commissural fibers interconnect the LVN. Projections of the LVN are primarily to spinal cord via the vestibulospinal tract (VST); collaterals of the VST terminate in the lateral reticular nucleus (LRN). Ascending uncrossed projections from LVN in the cat terminate in the medial rectus subdivision of the OMC.(ABSTRACT TRUNCATED AT 400 WORDS)
Study of the Small Vibrations of Six Particles in a System Analogous to the Benzene Ring

The system of six particles is allowed to vibrate under certain restrictions, assuming an elastic nature for the restoring forces. Frequencies of vibration are obtained and compared with Raman data lending some support to the Claus construction of the benzene molecule.
Epidermal Growth Factor Receptor Translocation to the Mitochondria: REGULATION AND EFFECT

Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src frequently occurs in human tumors and is linked to enhanced tumor growth. In experimental systems this synergistic growth requires EGF-dependent association of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src. A search for signaling mediators of Tyr(P)-845 revealed that mitochondrial cytochrome c oxidase subunit II (CoxII) binds EGFR in a Tyr(P)-845- and EGF-dependent manner. In cells this association involves translocation of EGFR to the mitochondria, but regulation of this process is ill-defined. The current study demonstrates that c-Src translocates to the mitochondria with similar kinetics as EGFR and that the catalytic activity of EGFR and c-Src as well as endocytosis and a mitochondrial localization signal are required for these events. CoxII can be phosphorylated by EGFR and c-Src, and EGF stimulation reduces Cox activity and cellular ATP, an event that is dependent in large part on EGFR localized to the mitochondria. These findings suggest EGFR plays a novel role in modulating mitochondrial function via its association with, and modification of CoxII.
An epidemic of proteinuria in Pima Indians with Type 2 diabetes mellitus

An epidemic of proteinuria in Pima Indians with Type 2 diabetes mellitus . Background The risk of proteinuria in Type 1 diabetes declined ≥30% over the past 50years, and improvements in metabolic control are believed to be largely responsible. Little is known about secular changes in the risk of proteinuria in Type 2 diabetes. Methods We examined trends in the incidence rate of proteinuria in Pima Indians ≥20years of age with diabetes diagnosed between January 1, 1955 and December 31, 1994. Results Among 1305 initially non-proteinuric diabetic subjects, 433 developed proteinuria during a median follow-up of 8.0years (range 0.8 to 30.2years). With subjects with diabetes diagnosed between 1955 and 1964 serving as the reference group, the rate of proteinuria was similar (rate ratio 1.0; 95% confidence interval, 0.79 to 1.3) in the cohort diagnosed between 1965 and 1974, 1.5 times as high (95% confidence interval, 1.1 to 2.0) in the cohort diagnosed between 1975 and 1984, and 1.9 times as high (95% confidence interval, 1.1 to 3.0) in the cohort diagnosed between 1985 and 1994, after adjusting for potential confounders in a generalized additive proportional hazards model. Between the first and last cohorts, plasma glucose concentration declined, on average, by 17% ( P = 0.0001) and the mean arterial pressure declined by 11% ( P = 0.0001). Conclusions The incidence rate of proteinuria in Pima Indians with Type 2 diabetes increased nearly twofold in the last 40years, despite improvements in plasma glucose and blood pressure. Rapidly changing environmental or behavioral factors must play an important role in the pathogenesis of diabetic renal disease in this population.
Role of Adenosine in Energy Supply/Demand Balance

Abstract The central paradigm of adenosine research is the idea that adenosine controls energy supply/demand balance. According to this theory, AMP is hydrolyzed to adenosine during conditions of hypoxia, ischemia, or exercise. Adenosine then redresses local energy deficits by reducing energy demand and increasing energy supply.
An exploration of spatial dispersion, pattern, and association of socio-economic functional units in an urban system

Hypotheses based on a set of socio-economic, cultural, and political functional units are examined. The geographic techniques employed in the study include spatial mean, standard distance, standard deviational ellipse, nearest neighbor analysis, and spatial analysis on a network: cross K function and network cross K function. The study not only explores the spatial pattern, distribution, and association of key socio-economic, cultural, and political units which could reveal internal structures and activities of an urban system, but also demonstrates a number of operational procedures that permit applications of traditional and advanced spatial analysis approaches in the study of real urban systems.
Transforming Complete Coverage Algorithms to Partial Coverage Algorithms for Wireless Sensor Networks

The complete area coverage problem in Wireless Sensor Networks (WSNs) has been extensively studied in the literature. However, many applications do not require complete coverage all the time. For such applications, one effective method to save energy and prolong network lifetime is to partially cover the area. This method for prolonging network lifetime recently attracts much attention. However, due to the hardness of verifying the coverage ratio, all the existing centralized or distributed but nonparallel algorithms for partial coverage have very high time complexities. In this work, we propose a framework which can transform almost any existing complete coverage algorithm to a partial coverage one with any coverage ratio by running a complete coverage algorithm to find full coverage sets with virtual radii and converting the coverage sets to partial coverage sets via adjusting sensing radii. Our framework can preserve the characteristics of the original algorithms and the conversion process has low time complexity. The framework also guarantees some degree of uniform partial coverage of the monitored area.
Circadian Clock Gene Expression in the Ovary: Effects of Luteinizing Hormone

A molecular device that measures time on a daily, or circadian, scale is a nearly ubiquitous feature of eukaryotic organisms. A core group of clock genes, whose coordinated function is required for this timekeeping, is expressed both in the central clock and within numerous peripheral organs. We examined expression of clock genes in the rat ovary. Transcripts for core oscillator elements (Arntl, Clock, Per1, Per2, and Cry1) were present in the ovary as indicated by quantitative real-time RT-PCR. Rhythmic expression patterns of Arntl and Per2 transcripts and protein products were out of phase with respect to the central oscillator and in complete antiphase to each other. Expression of Arntl was significantly elevated after the LH surge on the day of proestrus. Finally, hCG treatment induced cyclic expression of both Arntl and Per2 gene products in hypophysectomized, immature rats primed with eCG. Collectively, these data suggest that the core underpinnings of the transcriptional/translational feedback loop that drives circadian rhythmicity is present in the rat ovary. Furthermore, the study identifies LH as a potential regulator of circadian clock gene rhythms in the ovary.
RVboost: RNA-seq variants prioritization using a boosting method.

Motivation: RNA-seq has become the method of choice to quantify genes and exons, discover novel transcripts and detect fusion genes. However, reliable variant identification from RNA-seq data remains challenging because of the complexities of the transcriptome, the challenges of accurately mapping exon boundary spanning reads and the bias introduced during the sequencing library preparation. Method: We developed RVboost, a novel method specific for RNA variant prioritization. RVboost uses several attributes unique in the process of RNA library preparation, sequencing and RNA-seq data analyses. It uses a boosting method to train a model of ‘good quality’ variants using common variants from HapMap, and prioritizes and calls the RNA variants based on the trained model. We packaged RVboost in a comprehensive workflow, which integrates tools of variant calling, annotation and filtering. Results: RVboost consistently outperforms the variant quality score recalibration from the Genome Analysis Tool Kit and the RNA-seq variant-calling pipeline SNPiR in 12 RNA-seq samples using ground-truth variants from paired exome sequencing data. Several RNA-seq–specific attributes were identified as critical to differentiate true and false variants, including the distance of the variant positions to exon boundaries, and the percent of the reads supporting the variant in the first six base pairs. The latter identifies false variants introduced by the random hexamer priming during the library construction. Availability and implementation: The RVboost package is implemented to readily run in Mac or Linux environments. The software and user manual are available at http://bioinformaticstools.mayo.edu/research/rvboost/. Supplementary information: Supplementary data are available at Bioinformatics online.
Mechanisms by Which Childhood Personality Traits Influence Adult Well-Being

Children's personality traits have enduring effects that shape adult well-being. In particular, childhood conscientiousness influences core aspects of adult well-being: health, friendships, and mastery. Research is now examining the mechanisms by which early personality traits initiate and sustain particular life paths. These include mediating and moderating mechanisms that may operate during critical developmental periods or may build cumulatively over time. Future research would benefit from testing theoretically derived mechanisms for different traits and examining variables as they change over time, using both short- and long-term longitudinal designs over different life stages.
Ecosystem Processes Performed by Unionid Mussels in Stream Mesocosms: Species Roles and Effects of Abundance

Unionid mussels are a guild of freshwater, sedentary filter-feeders experiencing a global decline in both species richness and abundance. To predict how these losses may impact stream ecosystems we need to quantify the effects of both overall mussel biomass and individual species on ecosystem processes. In this study we begin addressing these fundamental questions by comparing rates of ecosystem processes for two common mussel species, Amblema plicata and Actinonaias ligamentina, across a range of abundance levels and at two trophic states (low and high productivity) in stream mesocosms. At both low and high productivity, community respiration, water column ammonia, nitrate, and phosphorus concentrations, and algal clearance rates were all linearly related to overall mussel biomass. After removing the effects of biomass with ANCOVA, we found few differences between species. In a separate series of experiments, nutrient excretion (phosphorus, ammonia, and molar N:P) and biodeposition rates were only marginally different between species. For the species studied here, functional effects of unionids in streams were similar between species and linearly related to biomass, indicating the potential for strong effects when overall mussel biomass is high and hydrologic residence times are long.
Pacemaker electrocardiogram with new large negative T waves: what is the cause?

Case report A 59-year-old woman with a history of severe nonischemic dilated cardiomyopathy with left bundle-branch block, status post implantation of a biventricular pacemaker-cardioverter-defibrillator (BiV/ICD) 3 years before, presented with atypical chest pain. She denied any recent physical or emotional stress. The patient had 2 cardiac catheterizations in the past without demonstrable coronary artery disease. After implantation of the BiV/ICD, her heart failure symptoms have essentially resolved, and her left ventricular ejection fraction has increased from 30% to 50%. On presentation, the patient's vital signs were normal, and her cardiovascular examination result was negative. Chest x-ray revealed trivial cardiomegaly and clear lung fields; the pacemaker and ICD leads were in the appropriate positions. Routine laboratory test results were normal. The admission electrocardiogram (ECG) demonstrated sinus P waves and a ventricular paced rhythm (Fig. 1A). Repeat ECG 8 hours later still showed a ventricular paced rhythm but now with large, almost giant negative T waves in the chest leads with more shallow negative T waves in the inferior leads (Fig. 1B). The patient did not experience any cardiac symptoms during the time interval between the 2 recorded ECGs. What could have been the cause of this dramatic change in the T-wave morphology over 8 hours?
Synthesis of 2,6‐dioxo‐3‐phthalimidopiperidine‐3,4,4,5,5‐d5 and 2,5‐dioxo‐3‐phthalimidopyrrolidine‐3,4,4‐d3 from L‐deuterio‐glutamic acid and L‐deuterio‐aspartic acid

The isolation and characterization of L -deuterio-glutamic acid and L -deuterio-aspartic acid from the ionic fraction of the hydrolysate of the algae Scenedesmus obliquus are described. These deuteriated amino acids were employed for the synthesis of 2,6-dioxo-3-phthalimidopiperidine-3,4,4,5,5- d 5 (VIII) and 2,5-dioxo-3-phthalimidopyrrolidine-3,4,4- d 3 (VII) which are analogs of thalidomide. The following sequence of reactions was utilized: phthaloylation with N -carbethoxy-phthalimide, heating with acetic anhydride, and heating with urea.
Information security with real-time operation: performance assessment for next generation wireless distributed networked-control-systems

Distributed network-control-systems (D-NCS) are a multidisciplinary effort whose aim is to produce a network structure and components that are capable of integrating sensors, actuators, communication, and control algorithms in a manner to suit real-time applications. They have been gaining popularity due to their high potential in widespread applications and becoming more realizable due to the rapid advancements in wireless communication and data transfer technologies. This paper addresses the issue of D-NCS information security as well its real-time performance with respect to network security protocols and encryption schemes. We use a wireless network based, robot navigation path tracking system called intelligent space (iSpace) as a D-NCS test bed in this paper. The paper classifies the data from every NCS module (sensors, actuators and controllers) according to bandwidth requirement, time and information sensitivity. We define performance parameters for this NCS test bed. Various system factors affecting these performance parameters are recognized. Network security algorithms DES and 3DES are integrated with the application to encrypt the sensitive information flow. These wireless security features are considered as an added factor to the NCS. Standard statistical approach (2k factorial experiment design) is used to study and estimate the effect of each factor on the system performance especially security additions. Thorough experimental results, tables of detailed characterization and effect estimate analysis is presented followed by the discussion on the performance comparison of NCS with and without wireless security.
In Vitro Fertilization and the Ethics of Nonconservative Medical Care

In 1991, the United States spent 13.2% --$751.8 billion-- of its gross domestic product (GDP) on health care.1 The expenditure curve is still rising, with $884.2 billion in 1993.2 Despite the amount devoted to health expenditures, over 14% of people living in the United States have no health insurance, and an even greater percentage are seriously underinsured.3 Although researchers disagree about how much technology has contributed to increasing health care costs, they generally agree that medical technology is one of the main reasons for this increment.4 Around 20% of health costs are spent on procedures and services that are, in many cases, clearly unnecessary such as caesarian sections, hysterectomies, laminectomies (back surgery), or diagnoses with magnetic resonance imaging.5
Asymptotic properties of Markov decision processes

In our earlier paper [1] we derived the optimal control policy for a time varying, finite horizon, continuous time Markov processes subject to a quadratic penalty on the amount of the rate adjustment. Some aspects of the time invariant, infinite horizon problem were resolved but questions remained. In this paper we consider a more general class of performance measures and constraints on the controls. After deriving the appropriate Hamilton-Jacobi equation, we discuss asymptotic properties. The central question here relates to the possibility of that non constant (e.g., periodic) steady state policies may have better average performance than the best constant policy.
Transform-domain adaptive filters: an analytical approach

Transform-domain adaptive filters refer to LMS filters whose inputs are preprocessed with a unitary data-independent transformation followed by a power normalization stage. The transformation is typically chosen to be the discrete Fourier transform (DFT), although other transformations, such as the cosine transform (DCT), the Hartley transform (DHT), or the Walsh-Hadamard transform, have also been proposed in the literature. The resulting algorithms are generally called DFT-LMS, DCT-LMS, etc. This preprocessing improves the eigenvalue distribution of the input autocorrelation matrix of the LMS filter and, as a consequence, ameliorates its convergence speed. In this paper, we start with a brief intuitive explanation of transform-domain algorithms. We then analyze the effects of the preprocessing performed in DFT-LMS and DCT-LMS for first-order Markov inputs. In particular, we show that for Markov-1 inputs of correlation parameter /spl rho//spl isin/[0,1], the eigenvalue spread after DFT and power normalization tends to (1+/spl rho/)l(1-/spl rho/) as the size of the filter gets large, whereas after DCT and power normalization, it reduces to (1+/spl rho/). For comparison, the eigenvalue spread before transformation is asymptotically equal to (1+/spl rho/)/sup 2//(1-/spl rho/)/sup 2/. The analytical method used in the paper provides additional insight into how the algorithms work and is expected to extend to other input signal classes and other transformations. >
Modulation of feline esophageal contractions by bolus volume and outflow obstruction

We studied the effect of bolus volume and esophageal obstruction on esophageal peristalsis by using synchronized video-fluoroscopic and manometric techniques in cats. A specially designed pressure cuff was surgically implanted around the distal esophagus to control the degrees of outflow obstruction. Secondary esophageal peristalsis was evoked by injecting bolus volumes of 3, 6, and 9 ml at cuff pressures of 0, 20, 40, and 60 mmHg. Increases in outflow obstruction reduced the velocity of peristalsis. The amplitude of esophageal contraction increased with increasing outflow obstruction at low bolus volumes but decreased with larger bolus volumes and larger outflow obstruction. In the absence of outflow obstruction, each esophageal contraction traversed the entire esophagus distal to its site of origin, but in the presence of outflow obstruction contractions only traversed part of the esophagus. The incidence and site of failure of propagation was directly related to cuff pressure and bolus volume. The relationship between the onset of manometric pressure complex at a given site in the esophagus to the passage of the bolus from that esophageal site was markedly affected by outflow obstruction. We conclude that esophageal peristalsis can be modulated by the bolus volume and outflow obstruction.
Accuracy of p-values of approximate tests in testing for equality of means under unequal variances

Seemingly, testing for fixed effects in linear models with variance-covariance components has been solved for decades. However, even in simple situations such as in fixed one-way model with heteroscedastic variances (a multiple means case of the Behrens-Fisher problem) the questions of statistical properties of various approximations of test statistics are still alive. Here we present a brief overview of several approaches suggested in the literature as well as those available in statistical software, accompanied by a simulation study in which the accuracy of p-values is studied. Our interest is limited here to the Welch’s test, the Satterthwaite-Fai-Cornelius test, the Kenward-Roger test, the simple ANOVA F-test, and the parametric bootstrap test. We conclude that for small sample sizes, regardless the number of compared means and the heterogeneity of variance, the ANOVA F-test p-value performs the best. For higher sample sizes (at least 5 per group), the parametric bootstrap performs well, and the Kenward-Roger test also performs well.
CORRECTING ESTIMATES OF ROOT CHEMICAL COMPOSITION FOR SOIL CONTAMINATION

The simplest method to correct estimates of root nutrient concentration for contamination by adhering soil is to express concentration on an “ash-free” basis—total sample nutrient divided by the ash-free mass of the sample. Such ash-free corrections can seriously inflate estimates of root nutrient concentration. Equations exist to correct estimates of plant composition for soil contamination, but they require information on the composition of the contaminating soil. Such information is difficult to obtain because soil fractions adhering to roots after washing may differ from whole soil. We developed a statistical method to estimate indirectly the composition of adhering soil by eliminating the correlation between estimates of plant composition and the degree of soil contamination. This method was tested against mixtures of grass shoots with soil, and then applied to roots from field-collected soil cores for two grass species. The estimated properties of the contaminating material differed from whole soil, and the differences were great enough to seriously affect root N estimates. The nature of the contaminating material may have to be determined for each new combination of soil and plant species. Our approach requires enough replicate samples for regression analysis but does not rely on separate soil samples and should be applicable over a wide range of experimental conditions.
Development of a decision-analytic model for the application of STR-based provenance testing of transrectal prostate biopsy specimens.

Abstract Background The diagnostic algorithm for most cancers includes the assessment of a tissue specimen by a surgical pathologist, but if specimen provenance is uncertain, the diagnostic and therapeutic process carries significant risk to the patient. Over the last decade, short tandem repeat (STR) analysis has emerged as a DNA-based method with clinical applicability for specimen identity testing (also known as specimen provenance testing). Although the clinical utility of identity testing using STR-based analysis has been demonstrated in many studies, its economic value has not been established. Methods We developed a decision-analytic model of the application of STR-based provenance testing of transrectal prostate biopsy specimens obtained as part of routine clinical care to rule out the presence of adenocarcinoma of the prostate, as compared with no STR-based testing. Using parameter values drawn from the published literature, the cost-effectiveness of STR-based testing was quantified by calculating the incremental cost-effectiveness ratio per quality-adjusted life-year gained. Results In comparison to the current standard practice of no identity testing, identity testing by STR-based analysis has an incremental cost-effectiveness ratio of $65,570 per quality-adjusted life-year gained at a testing cost of $618 per person. At a cost of $515 per person, identity testing would meet the conservative standard of $50,000 per quality-adjusted life-year. At a test cost of $290 per person, identity testing would be cost saving. Conclusion Given the rapidly declining pricing of STR-based identity testing, it is likely that testing to confirm the identity of positive prostate biopsy samples will be a cost-effective method for preventing treatment errors stemming from misidentification. Studies to formally establish the frequency of specimen provenance errors in routine clinical practice would therefore seem justified.
Targeting the Consequences of the Metabolic Syndrome in the Diabetes Prevention Program

This review describes the effect of lifestyle change or metformin compared with standard care on incident type 2 diabetes and cardiometabolic risk factors in the Diabetes Prevention Program and its Outcome Study. The Diabetes Prevention Program was a randomized controlled clinical trial of intensive lifestyle and metformin treatments versus standard care in 3234 subjects at high risk for type 2 diabetes. At baseline, hypertension was present in 28% of subjects, and 53% had metabolic syndrome with considerable variation in risk factors by age, sex, and race. Over 2.8 years, type 2 diabetes incidence fell by 58% and 31% in the lifestyle and metformin groups, respectively, and metabolic syndrome prevalence fell by one-third with lifestyle change but was not reduced by metformin. In placebo- and metformin-treated subjects, the prevalence of hypertension and dyslipidemia increased during the Diabetes Prevention Program, whereas lifestyle intervention slowed these increases significantly. During long-term follow-up using modified interventions, type 2 diabetes incidence decreased to ≈5% per year in all groups. This was accompanied by significant improvement in cardiovascular disease risk factors over time in all treatment groups, in part associated with increasing use of lipid-lowering and antihypertensive medications. Thus a program of lifestyle change significantly reduced type 2 diabetes incidence and metabolic syndrome prevalence in subjects at high risk for type 2 diabetes. Metformin had more modest effects.
Learning dynamic audio-visual mapping with input-output Hidden Markov models

In this paper, we formulate the problem of synthesizing facial animation from an input audio sequence as a dynamic audio-visual mapping. We propose that audio-visual mapping should be modeled with an input-output hidden Markov model, or IOHMM. An IOHMM is an HMM for which the output and transition probabilities are conditional on the input sequence. We train IOHMMs using the expectation-maximization(EM) algorithm with a novel architecture to explicitly model the relationship between transition probabilities and the input using neural networks. Given an input sequence, the output sequence is synthesized by the maximum likelihood estimation. Experimental results demonstrate that IOHMMs can generate natural and good-quality facial animation sequences from the input audio.
The role of head computer tomographic scans on the management of MICU patients with neurological dysfunction.

Neurological dysfunction is common in patients admitted to the medical intensive care unit (MICU). However, the indications for head imaging in those patients are unclear. The objective of this study was to assess whether clinical variables would be useful in selecting patients who are likely to have an abnormality on head computerized tomographic (CT) scanning and to determine the impact of such scans on management decisions. We reviewed the charts of 740 patients admitted to our MICU between October 2002 and July 2004. A total of 123 patients (16.6%) had a head CT scan performed, with a new finding being present in 26 (21.1%) patients. In the patients with a new CT finding, there was a change in diagnosis in 11 (42%) patients and a change in treatment in 6 (23%) patients. Logistic regression analysis failed to determine any clinical characteristic that could predict a new finding on the CT scan. This study suggests that clinicians should have a low threshold for ordering a CT scan in MICU patients with ...
Patterns of Care for Patients with Chronic Kidney Disease in the United States: Dying for Improvement

The burden of chronic kidney disease can be assessed by multiple criteria that underscore the need for improved detection, treatment, and outcome monitoring. Several process measures for the care of advanced CKD patients are examined herein. Twenty seven and 11% of patients with CKD in National Health and Nutrition Examination Surveys (NHANES) III had BP 15% of the prevalent patients are treated by peritoneal dialysis across the country. Despite survival and quality-of-life benefits with transplantation, most eligible recipients in the United States have not been placed on a transplant waiting list 6 mo after beginning dialysis. Last, <40% of incident ESRD patients in the United States have received the recommended frequency of mammography, PAP examinations, or prostate-specific antigen (PSA) or HbA1c measurements. These deficiencies in care for patients with advanced CKD likely adversely influence the survival of US ESRD patients. Contemporary outcome information supports this contention. CKD patients referred to a nephrologist for the first time within 90 d of the start of dialysis have an approximately 40% to 60% increased risk of death during their first year of renal replacement therapy (RRT). Thirty-five percent of CKD patients are seen within 90 d of receiving RRT. In addition, if fewer than five nephrology visits occur, death risks are increased by 15%. These findings confirm the urgent need for improvement in healthcare delivery for CKD patient in the United States.
Private value auctions: A first look

This chapter introduces the basic methodology of auction theory. The relative performance of the auction formats on grounds of revenue or efficiency is evaluated by comparing the equilibrium outcomes in one format versus another. Under a first-price sealed-bid auction, the highest bidder gets the object and pays the amount he bid. Under second-price sealed-bid auction, the highest bidder gets the object and pays the second highest bid. The strategic problem confronting bidders in second-price auctions is much simpler than that in first-price auctions, so they constitute a natural starting point. Also recall that in the private values framework, second-price auctions are equivalent to open ascending price auctions. In a first-price auction, equilibrium behavior is more complicated than in a second-price auction. Clearly, no bidder would bid an amount equal to his or her value as this would only guarantee a payoff of zero. In this case, the equilibrium strategy calls upon a bidder to bid a constant fraction of his value.
Human Platelet Gαq Deficiency Is Associated with Decreased Gαq Gene Expression in Platelets but not Neutrophils

G-proteins play an important role in platelet signal transduction and regulate responses upon activation of G-protein coupled receptors (GPCR). We have previously reported a patient with impaired platelet responses associated with deficiency in platelet Galphaq. To understand the molecular basis for this defect, the cDNA sequence encoding Galphaq (1080 bp) was obtained by reverse-transcription and polymerase chain reaction of platelet RNA; the cDNA sequence showed no mutations in the patient. Platelet Galphaq mRNA levels were decreased by >50% compared to normal subjects; platelet Galphai2 mRNA levels were normal. Neutrophil calcium mobilization and elastase secretion, upon activation with several agonists, and neutrophil Galphaq mRNA and protein levels were normal. These studies demonstrate that the patient has a defect in Galphaq gene expression in platelets but not neutrophils, possibly due to defects in transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage specific defect.
Incidental Captures of Eastern Spotted Skunk in a High-Elevation Red Spruce forest in Virginia

Abstract Spilogale putorius (Eastern Spotted Skunk) is considered rare in the southern Appalachian Mountains and throughout much of its range. We report incidental captures of 6 Eastern Spotted Skunks in a high-elevation Picea rubens (Red Spruce) forest in southwestern Virginia during late February and March 2014. At 1520 m, these observations are the highest-elevation records for Eastern Spotted Skunk in the Appalachian Mountains. They are also the first known records of this species using Red Spruce forests in the southern Appalachians.
Abstract 716: O6-Methylguanine DNA methyl transferase (MGMT) and tamoxifen resistance in patients with breast cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Tamoxifen is an estrogen receptor antagonist in breast tissue. It has been used as a hormonal therapy for early and advanced breast cancer both in premenopausal and postmenopausal patients with estrogen receptor positive breast cancer. Acquired resistance to tamoxifen therapy is a common therapeutic encounter. Different mechanisms for Tamoxifen resistance have been postulated. In the present study we investigated if over expression of MGMT causes tamoxifen resistance in breast cancer patients. Purpose: We sought to determine MGMT expression levels in various breast cancer cell lines as well as in breast cancer patient's samples before and after treatment with tamoxifen. Experimental Design: MGMT expression levels were compared in breast cancer tissue samples obtained from patients before starting treatment with Tamoxifen and after tumor progression due to development of Tamoxifen resistance. MGMT expression level was evaluated using western blot and immunohistochemical assays. Several commercial breast cell lines were evaluated for expression of MGMT. Results: We found that MGMT is over expressed in the majority of breast cancer cell lines compared to normal breast epithelial cells. Compared to pre Tamoxifen treatment, post Tamoxifen treated breast cancer patient samples have significantly higher levels of MGMT expression. Conclusion: Collectively, our results demonstrate that breast cancer cells showed significantly higher levels of MGMT expression and furthermore, Tamoxifen treatment induces further MGMT over expression in breast cancer patients. According to our results over expression of MGMT is a possible cause for Tamoxifen resistance. Inhibition of MGMT might overcome Tamoxifen resistance and restore breast cancer sensitivity to Tamoxifen treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 716. doi:10.1158/1538-7445.AM2011-716
Inhibition of growth of Streptococci by adenine.

SummaryAdenine, at a concentration of 5 μg/ml or above in a synthetic medium, has been shown to inhibit growth of 2 strains of S. pyogenes, S23 and C203U. The inhibition can be overcome by addition of xanthine, guanine or hypoxanthine at approximately one-third the molar concentration of the inhibitor.
Photodriven charge separation dynamics in CdSe/ZnS core/shell quantum dot/cobaloxime hybrid for efficient hydrogen production.

Photodriven charge-transfer dynamics and catalytic properties have been investigated for a hybrid system containing CdSe/ZnS core/shell quantum dots (QDs) and surface-bound molecular cobaloxime catalysts. The electron transfer from light-excited QDs to cobaloxime, revealed by optical transient absorption spectroscopy, takes place with an average time constant of 105 ps, followed a much slower charge recombination process with a time constant of ≫3 ns. More interestingly, we also observed photocatalytic hydrogen generation by this QD/cobaloxime hybrid system, with >10 000 turnovers of H2 per QD in 10 h, using triethanolamine as a sacrificial electron donor. These results suggest that QD/cobaloxime hybrids succeed in coupling single-photon events with multielectron redox catalytic reactions, and such systems could have potential applications in long-lived artificial photosynthetic devices for fuel generation from sunlight.
99Mo Separation from High-Concentration Irradiated Uranium Nitrate and Uranium Sulfate Solutions

We report separation data indicating that 99Mo can be separated from a vast excess of either uranyl sulfate or uranyl nitrate in irradiated dilute acid solutions. These results suggest that, if medical isotope 99Mo is produced during fission of high concentrations of low enriched uranium sulfate solution fuel, it is feasible to both recover >90% of the 99Mo for further purification and the uranium for recycle.