cssi/SciSciGPT-SciSciNet huggingface dataset:
FUNCTIONAL SYNCARPY BY INTERCARPELLARY GROWTH OF POLLEN TUBES IN A PRIMITIVE APOCARPOUS ANGIOSPERM, ILLICIUM FLORIDANUM (ILLICIACEAE)'

Fluorescence microscopy and histological studies have been used to show that in Illicium floridanum Ellis (Illiciaceae), a primitive apocarpous angiosperm, functional syncarpy is achieved by intercarpellary growth of pollen tubes. After pollen germinates on the separate stigmatic crests of the carpellary whorl, tubes grow within the carpels obliquely down and inward toward the central floral axis which is modified as a stigmalike "apical residuum." In a restricted shallow region around the base of the apical residuum, some pollen tubes grow out between the unfused margins of the carpels and circumferentially around the surface of the apical residuum from where they may enter neighboring carpels. Some pollen germination and tube growth also occur on the apical residuum itself. The apical residuum with its associated unfused carpel margins acts as an extragynoecial compitum for pollen tube transfer between carpels, and, as such, is believed to represent a mechanism for increasing the efficiency of seed set. The pollen tube pathway of Illicium appears to be a primitive expression of a line of evolutionary development leading to syncarpous gynoecia through stages possibly exemplified by certain members of the Trochodendraceae (lower Hamamelididae).
Characteristics and outcomes of heart failure-related intensive care unit admissions in children with cardiomyopathy.

Objective: The purpose of this study was to describe patient characteristics and outcomes of heart failure (HF)erelated intensive care unit (ICU) hospitalizations in children with cardiomyopathy (CM). Methods and Results: A query of the Pediatric Health Information System database, a large administrative and billing database of 43 tertiary children’s hospitals, was performed. A total of 17,309 HF-related ICU hospitalizations from 2005 to 2010 of 14,985 children #18 years old were analyzed. Of those, 2,058 (12%) hospitalizations for CM-HF in 1,599 (11%) children were identified. Classification into CM subtypes was not possible owing to database limitations. The number of yearly CM-HF hospitalizations significantly increased during the study period (P 5 .036). Overall mortality was 11%, and cardiac transplantation occurred in 20% of hospitalizations. Mechanical circulatory support (MCS) was used in 261 (13%) of hospitalizations. Renal failure, MCS, respiratory failure, sepsis, and vasoactive medications were associated with mortality on multivariable analysis. Significant comorbidities associated with these hospitalizations included arrhythmias in 42%, renal failure in 13%, cerebrovascular disease in 6%, and hepatic impairment in 5%. Conclusions: HF-related ICU hospitalizations in children with cardiomyopathy are increasing. These children are at high risk for poor outcomes with an in-hospital mortality of 11%. (J Cardiac Fail 2013;19:672e677)
Nonlinear laser interactions with saltwater aerosols

Intensity ratios of the resonant Na((lambda) equals 589 nm) to H(alpha ) ((lambda) equals 656 nm) emission lines have been measured for 10 GW/cm2 KrF laser radiation ((lambda) = 248 nm, tpulse equals 17 ns) interacting with 50 micrometers diameter saltwater droplets as a function of position in the breakdown region parallel to the incident laser beam. Results indicate the H(alpha ) emission intensity is highly non-uniform through the plasma plume and is highest in the plume ejected back toward the laser beam. In contrast, the Na emission line intensity shows a much weaker spatial dependence as a function of position within the plasma plume. Calibration data are also reported for the ratio of Na to H(alpha ) emission intensities as a function of Na concentration (0-2000 ppm) for approximately equals 20 micrometers diameter monodisperse droplets located at a fixed observation point in the plasma plume. Future research will extend the ratioing technique to remotely measure droplet salt concentrations in polydisperse saltwater sprays.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
The logic of questions and its relevance to instructional science

This paper discusses the notion of a logic of questions, its relevance to instructional science, and the problems involved in developing a logic of questions that will be adequate from the standpoint of instructional science. Several systems of question logic — particularly those of Belnap and Aqvist — are noted. The notion of pedagogical question, in a wide sense of “pedagogical”, is discussed. A system adequate to deal with pedagogical questions will be an erotetic logic in a wide sense of “erotetic”, covering not only individual interrogative sentences but also sets of sentences of various kinds, and sets of appropriate replies of various kinds. An erotetic logic of this sort is outlined in the paper and more fully in the Appendix. Questions are then raised concerning its adequacy.
Biochemical factors affecting the tightness of 5-fluorodeoxyuridylate binding to human thymidylate synthetase.

Abstract Ligand binding studies of thymidylate synthetase (5,10-methylenetetrahydrofolate: deoxyuridylate C -methyltransferase, EC 2.1.1.45) isolated from CCRF-CEM human lymphoblastic leukemia cells were conducted to examine the mechanism of 5-fluorodeoxyuridylate (FdUMP) binding to the human enzyme in the presence of L -1-(+)-5,10-methylenetetrahydrofolate (5,10-CH 2 H 4 PteGlu) and to assess biochemical factors which could account for decreased binding of FdUMP by the enzyme in cells and tissues. Scatchard plots showed one class of binding sites for FdUMP with an apparent dissociation constant ( K D ) of 3.1 × 10 −11 M in the absence, and 3.5 × 10 −10 M in the presence, of 80 mM potassium phosphate (P i ). The observed rate constant for FdUMP association ( k on obs ) was dependent on the 5,10-CH 2 H 4 PteGlu concentration and attained a maximal value of 1.7 × 10 8 M −1 min −1 at a concentration of ca . 12μM 5,10-CH 2 H 4 PteGlu. Increasing the concentration of 5,10-CH 2 H 4 PteGlu decreased the apparent rate constant of FdUMP dissociation ( k off obs ), although FdUMP had no effect on the rate of 5,10-CH 2 H 4 PteGlu dissociation. These studies showed that CCRF-CEM thymidylate synthetase has an ordered mechanism of ligand binding and release, with the nucleotide binding first and dissociating last. Incubation of the enzyme-FdUMP-5,10-CH 2 H 4 PteGlu ternary complex with the substrate dUMP resulted in renewal of enzyme activity at about the same rate as that of FdUMP release. Nucleotides, deoxyuridine (dUrd), and polyoxyanions decreased the rate of FdUMP association but had no significant effect on the rate of FdUMP dissociation. dUMP was the most potent inhibitor of FdUMP binding found, with a binding constant determined from competition experiments of 0.36 μM compared to a Michaelis constant of 2.8 μM. The binding constant for p i was determined similarly to be 10 mM. The effects of dUMP plus P i , on decreasing the rate of FdUMP association were additive, whereas the combined effects of dUMP and sub-optimal concentrations of 5,10-CH 2 H 4 PteGlu were not additive, but multiplicative or greater. The levels of dUMP, P i , and 5,10-CH 2 H 4 PteGlu that reportedly are present in some cells and tissues, theoretically could increase the K D to more than 10 −6 M. These results could account for the coexistence of substantial levels of FdUMP and unbound thymidylate synthetase found in some cells and tissues.
PrCu5−xIn1+x [x = 0.24 (1)] with the orthorhombic CeCu6 structure type

Large single crystals of the title compound were synthesized from the corresponding elements using an eutectic Cu/In mixture as a solvent. PrCu5−xIn1+x [x = 0.24 (1)] is a new ternary derivative of the orthorhombic CeCu6 structure type [space group Pnma (No. 62)]. This result contradicts the findings of Kalychak et al. [(1988). Dop. Akad. Nauk Ukr. RSR Ser. B, 9, 39–42], who found that CeCu4.38In1.62 belongs to a new structure type (space group Pnnm), derived from the parent CeCu6 compound by doubling the a axis. In the present structure, all the atoms except one of the Cu species occupy special positions with mirror symmetry.
Physicochemical Characteristics and Droplet Impact Dynamics of Superhydrophobic Carbon Nanotube Arrays

The physicochemical and droplet impact dynamics of superhydrophobic carbon nanotube arrays are investigated. These superhydrophobic arrays are fabricated simply by exposing the as-grown carbon nanotube arrays to a vacuum annealing treatment at a moderate temperature. This treatment, which allows a significant removal of oxygen adsorbates, leads to a dramatic change in wettability of the arrays, from mildly hydrophobic to superhydrophobic. Such change in wettability is also accompanied by a substantial change in surface charge and electrochemical properties. Here, the droplet impact dynamics are characterized in terms of critical Weber number, coefficient of restitution, spreading factor, and contact time. Based on these characteristics, it is found that superhydrophobic carbon nanotube arrays are among the best water-repellent surfaces ever reported. The results presented herein may pave a way for the utilization of superhydrophobic carbon nanotube arrays in numerous industrial and practical applications, including inkjet printing, direct injection engines, steam turbines, and microelectronic fabrication.
Ultrastructure of degenerating cerebellothalamic terminals in the ventral medial nucleus of the cat.

Terminal degeneration of cerebellar afferents in the ventral medial thalamic nucleus (VM) was studied in cats at the ultrastructural level after uni- or bilateral lesions in the brachium conjunctivum (BC). To achieve discrete lesions within the BC, a new very accurate stereotaxic technique was used. Numerous large terminals belonging to a population of so-called LR boutons were observed degenerating in the VM. The boutons displayed a wide variety of degenerative changes. Some revealed the features of the classical neurofilamentous type of degeneration. Others, although containing a slightly increased number of neurofilaments, featured much more prominently large numbers of coated vesicle shells and heavy accumulations of a flocculent electrondense material. Degeneration in a third group of boutons similar to some extent to the light type of degeneration was characterized by tight clumping of enormously swollen or distorted synaptic vesicles within a light matrix. At later stages, however, all these boutons were believed to become shrunken and electron-dense since intermediate stages between the light- and dark-appearing boutons were observed. The degenerating cerebellar boutons formed asymmetrical synaptic contacts. Groups of 3 or 4 boutons terminated upon dendrites of projection neurons synapsing more frequently on spines than on dendritic stems. The synaptic contacts between cerebellar boutons and the vesicle-containing dendrites of local circuit neurons were encountered as often if not more than the contacts on projection neuron dendrites. Triads consisting of cerebellar boutons and dendrites of both types of neurons were observed very regularly. This synaptic arrangement provides the anatomical basis for the modification of cerebellar input in the VM by interneurons.
A case of anomalous right coronary artery to right atrial fistula presenting as atypical aortic insufficiency

Abstract A case of anomalous right coronary artery to right atrial fistula is described. The principal auscultatory finding was an aortic regurgitant blowing murmur with maximal radiation to the third right intercostal space at the sternal border. The relation of the aortic valvular insufficiency demonstrated angiographically to the coronary fistula was not clear.
Convection induced by surface-tension gradients: experiments with a heated point source

Abstract An exploratory investigation of convective flows in heated liquid layers has uncovered a number of curious phenomena. With steady heating from below, at a point, oscillating temperature and velocity fields have been observed in thin horizontal films. Apparently, the motions are driven by surface-tension gradients. The addition of an elastic monolayer at the free liquid surface revealed a further class of unusual flow patterns.
Analysis of the borehole televiewer log from DSDP hole 395A: Results from the Dianaut Program

The French wireline re-entry expedition known as DIANAUT culminated in the successful completion of a series of downhole measurements in three Deep Sea Drilling Project (DSDP) holes in the north-central Atlantic Ocean. Among these measurements was a borehole televiewer (BHTV) log obtained in Hole 395A from bottom of casing at 112 meters below seafloor (mbsf) to a depth of 605 mbsf. In contrast with a BHTV survey previously conducted in this well during DSDP Leg 78B in 1981, televiewer data were not degraded by random cable oscillations due to ship heave and the quality of this log is excellent. These latest data were digitized and processed in terms of acoustic travel time and amplitude to compute hole size and shape, evaluate the structural integrity of the surrounding rock, and characterize intersecting fractures. The acoustic caliper and reflectivity logs correlate well with the lithologic column, particularly at the boundaries between major units which often are marked by breccias. Fractures in the lower part of the hole appear to be effectively sealed, in contrast with the open fractures identified in the upper sections. This supports a systematic pattern derived from complementary geophysical logs of increasing density, electrical resistivity, and elastic-wave velocity, and decreasing in situ permeability as a function of depth. Fractures intersecting the well exhibit a wide range of orientations marked by some clustering of dip azimuths approximately east-west. The presence of moderately dipping fractures striking subparallel to the ridge axis is consistent with both ridge-parallel topographic elongations observed in this area and with azimuthal seismic anisotropy reported elsewhere, suggesting that fractures such as those identified from the BHTV record contribute to these effects.
Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

Inflammation is associated with Aβ pathology in Alzheimer's disease (AD) and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months) Tg2576 mice to a response that reduces Aβ pathology. TG (n = 29) and WT (n = 27) mice were divided into sedentary (SED) and exercised (RUN) groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED) mice than in wildtype (WTSED) (p = 0.04, p = 0.006). Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07). Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01) and soluble fibrillar Aβ (p = 0.01) were observed in the exercised transgenic animals. Exercise shifts the immune response from innate to an adaptive or alternative response. This shift in immune response coincides with a decrease in Aβ in advanced pathological states.
QGene 4.0, an extensible Java QTL-analysis platform

Summary: Of many statistical methods developed to date for quantitative trait locus (QTL) analysis, only a limited subset are available in public software allowing their exploration, comparison and practical application by researchers. We have developed QGene 4.0, a plug-in platform that allows execution and comparison of a variety of modern QTL-mapping methods and supports third-party addition of new ones. The software accommodates line-cross mating designs consisting of any arbitrary sequence of selfing, backcrossing, intercrossing and haploid-doubling steps that includes map, population, and trait simulators; and is scriptable. Availability: Software and documentation are available at http://coding.plantpath.ksu.edu/qgene. Source code is available on request. Contact: jcn@ksu.edu
Liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients

Liposomal amphotercin B was compared with conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients in a randomized, double-blind, multicentre trial. Using a composite end-point, the two drugs were equivalent in overall efficacy. However, the liposomal amphotericin B treatment group had fewer proven fungal infections, fewer infusion-related side effects and less nephrotoxicity. Patient data from that study were analysed to compare the pharmacoeconomics of liposomal versus conventional amphotericin B therapy. Itemized billing data from 414 patients were collected and analysed. Hospital costs from first dose were significantly higher for all patients who received liposomal amphotericin B ($48,962 versus $43,183, P = 0.02). However, hospital costs were very sensitive to the cost of the study medication ($39,648 versus $43,048, when acquisition costs are not included, P = 0.4). Using decision analysis models and sensitivity analyses to vary the cost of study medications and risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients, and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients. Therefore, the drug acquisition costs and the risk of nephrotoxicity are important factors in determining the cost-effectiveness of liposomal amphotericin B as empirical therapy in persistently febrile neutropenic patients. In a recent randomized double-blind study comparing liposomal amphotericin B at 3 or 5 mg/kg/day with amphotericin B lipid complex (ABLC) 5 mg/kg/day as empirical antifungal treatment in patients with febrile neutropenia, liposomal amphotericin B was associated with less toxicity than ABLC, both in terms of infusion-related reactions and nephrotoxicity. The incidence of study drug discontinuation due to toxicity was: liposomal amphotericin B 3 mg/kg/day, 14%; liposomal amphotericin B 5 mg/kg/day, 15%; and ABLC, 42% (P < 0.001).
Total operational efficiency (TOE): the determination of two capacity and cycle time components and their relationship to productivity improvements in a semiconductor manufacturing line

Short cycle time manufacturing (SCM) concepts have been developed to help understand and manage the performance of a manufacturing line. SCM assumes that each tool/toolset (and hence the overall line) can be described by a performance curve that relates cycle time to throughput, with cycle time increasing non-linearly as throughput approaches capacity. Productivity improvements are realized by reducing the components of capacity loss, which increases the overall capacity and, thus, shifts the performance curve. To implement SCM, all major components of capacity loss must be defined, including the primary driver for cycle time: idle-no-WIP. In order to achieve this, the analysis must look beyond a strictly tool-centric focus to a system view focus so that the interaction between the tool, operator, work-in-progress, etc., can be included in the components of capacity loss. This paper develops and explains total operational efficiency (TOE), which is a key component of SCM. TOE describes the capacity and cycle time components of a tool/toolset in a self-consistent and hierarchical way that reflect a system level view and where the interaction of the tool, operator, WIP, etc., are taken into account. Once these components and their relationship have been defined, it is then possible to more clearly articulate responsible owners and assess the possibility of improvement. The reality of most semiconductor manufacturing lines is that tool availability is rarely the largest detractor from capacity. Instead, other issues such as the amount of automation, line layout, cycle time requirements, technology mix, etc., become the prime determiners of the effective capacity. In addition, TOE enables meaningful comparisons to be made between different lines and for the better tracking of improvements over time in any given line on a component by component basis.
Scalable Biologically Inspired Neural Networks with Spike Time Based Learning

This paper describes the software and algorithmic issues involved in developing scalable large-scale biologically inspired spiking neural networks. These neural networks are useful in object recognition and signal processing tasks, but will also be useful in simulations to help understand the human brain. The software is written using object oriented programming and is very general and usable for processing a wide range of sensor data and for data fusion.
Uncertainty Learning Using SVMs and CRFs

In this work, we explore the use of SVMs and CRFs in the problem of predicting certainty in sentences. We consider this as a task of tagging uncertainty cues in context, for which we used lexical, wordlist-based and deep-syntactic features. Results show that the syntactic context of the tokens in conjunction with the wordlist-based features turned out to be useful in predicting uncertainty cues.
MOLECULAR MECHANISMS OF BACTERIOCIN EVOLUTION

Microorganisms are engaged in a never-ending arms race. One consequence of this intense competition is the diversity of antimicrobial compounds that most species of bacteria produce. Surprisingly, little attention has been paid to the evolution of such extraordinary diversity. One class of antimicrobials, the bacteriocins, has received increasing attention because of the high levels of bacteriocin diversity observed and the use of bacteriocins as preservatives in the food industry and as antibiotics in the human health industry. However, little effort has been focused on evolutionary questions, such as what are the phylogenetic relationships among these toxins, what mechanisms are involved in their evolution, and how do microorganisms respond to such an arsenal of weapons? The focus of this review is to provide a detailed picture of our current understanding of the molecular mechanisms involved in the process of bacteriocin diversification.
Information Content of U.S. Treasury Inflation-Indexed Bonds

U.S. Treasury inflation-indexed bonds are designed to provide a stable real return before taxes. A comparison between these bonds and conventional bonds reveals that the effective real yield of U.S. Treasury inflation-indexed bonds is attractive. The econometric results suggest, however, that the real rate provided by U.S. Treasury inflation-indexed bonds is not independent of inflation, implying that the Fisher hypothesis is contradicted by the data. An implication of negative correlation between the real rate and inflation is that the time to buy U.S. Treasury inflation-indexed bonds is when inflation is low. While the yields on U.S. Treasury inflation-indexed bonds are shown to reflect inflation by a lag of about one month, nominal interest rates do not fully adjust to inflation.
Soluble forms of tau are toxic in Alzheimer’s disease

Accumulation of neurofibrillary tangles (NFT), intracellular inclusions of fibrillar forms of tau, is a hallmark of Alzheimer’s disease. NFT have been considered causative of neuronal death, however, recent evidence challenges this idea. Other species of tau, such as soluble misfolded, hyperphosphorylated, and mislocalized forms, are now being implicated as toxic. Here we review the data supporting soluble tau as toxic to neurons and synapses in the brain and the implications of these data for development of therapeutic strategies for Alzheimer’s disease and other tauopathies.
Polyamine synthesis and interconversion by the Microsporidian Encephalitozoon cuniculi.

Abstract Polyamines are small cationic molecules necessary for growth and differentiation in all cells. Although mammalian cells have been studied extensively, particularly as targets of polyamine antagonists, i.e. antitumor agents, polyamine metabolism has also been studied as a potential drug target in microorganisms. Since little is known concerning polyamine metabolism in the microsporidia, we investigated it in Encephalitozoon cuniculi, a microspordian associated with disseminated infections in humans. Organisms were grown in RK-13 cells and harvested using Percoll gradients. Electron microscopy indicated that the fractions banding at 1.051–1.059/g/ml in a microgradient procedure, and 1.102–1.119/g/ml in a scaled-up procedure were nearly homogenous, consisting of pre-emergent (immature) spores which showed large arrays of ribosomes near polar filament coils. Intact purified pre-emergent spores incubated with [3H] ornithine and methionine synthesized putrescine, spermidine, and spermine, while [14C]sp...
Molecular Investigation of Age-Related Changes in Mouse Endocrine Pancreas

Aging is an etiologic factor in non-insulin-dependent diabetes mellitus. While the effect of aging on insulin secretion has been described by several classic studies, the characterization of the molecular basis offi-cell abnormalities is stilt under way. We recently demonstrated in rats that aging is associated not only with a reduction in insulin secretion but also with diminished levels of intracellular insulin content and the mRNA for insulin. In this study, we investigated whether the molecular abnormalities previously described in the rat /3 cell were also present in the mouse (C57BL/6J). Total cellular RNA was isolated from individual pancreata of 3-, 9-, and 30-month-old mice (n = 6 per age group). Samples were subjected to slot-blot analysis by using homologous probes for insulin, glucagon, somatostatin, glucose transporter-2 (glut-2), glucokinase, elastase-l, and fi-actin. We observed a progressive age-dependent decrease in insulin mRNA levels: insulin mRNA levels decreased by 40% with age (p = .007). This paralleled decreases in glut-2 (p = .001) mRNA levels, but it was in contrast with glucokinase mRNA levels which increased markedly (p = .0003). Somatostatin mRNA levels were unchanged, glucagon mRNA levels decreased modestly (p = .01), and mRNA levels for elastase-l and fi-actin increased with age (p = .0001 for either one). In summary, it appears that in the mouse a progressive decline in the activity of the endocrine pancreas occurs with aging. This phenomenon seems to affect only the ft cells and not the dor S cells of the islet ofLangerhans or the exocrine pancreas. This progressive decline may represent the biological features of the age-dependent risk for the development of diabetes.
Studies of folding and misfolding using simplified models.

Computer simulations are as vital to our studies of biological systems as experiments. They bridge and rationalize experimental observations, extend the experimental ‘field of view’, which is often limited to a specific time or length scale, and, most importantly, provide novel insights into biological systems, offering hypotheses about yet-to-be uncovered phenomena. These hypotheses spur further experimental discoveries. Simplified molecular models have a special place in the field of computational biology. Branded as less accurate than all-atom protein models, they have offered what all-atom molecular dynamics simulations could not — the resolution of the length and time scales of biological phenomena. Not only have simplified models proven to be accurate in explaining or reproducing several biological phenomena, they have also offered a novel multiscale computational strategy for accessing a broad range of time and length scales upon integration with traditional all-atom simulations. Recent computer simulations of simplified models have shaken or advanced the established understanding of biological phenomena. It was demonstrated that simplified models can be as accurate as traditional molecular dynamics approaches in identifying native conformations of proteins. Their application to protein structure prediction yielded phenomenal accuracy in recapitulating native protein conformations. New studies that utilize the synergy of simplified protein models with all-atom models and experiments yielded novel insights into complex biological processes, such as protein folding, aggregation and the formation of large protein complexes.
Foodborne and waterborne zoonotic sarcocystosis

Abstract The ingestion of raw beef or pork infected with Sarcocystis can cause illness in humans. Nausea and vomiting can occur within three days of consuming infected meat; these symptoms are considered due to toxic substances in sarcocysts or to other factors in raw meat. Diarrhea and abdominal pain are associated with excretion of sporulated sporocysts in human feces usually within 8–14 days after ingestion of infected meat. The intestinal phase is often self-limiting but sporocysts may be excreted for months. There appears to be little or no immunity to excretion of sporocysts after ingesting each infected meal. The clinical illness is more severe after eating infected pork versus infected beef. There is one zoonotic Sarcocystis species in pork, Sarcocystis suihominis, with domestic and wild pigs as intermediate hosts. Two zoonotic species are present in cattle, Sarcocystis hominis, and Sarcocystis heydorni; neither has been recognized in North America. Although isolated human cases of muscular sarcocystosis have been known for more than 100 years, recently a mysterious serious, diagnostically challenging illness has been reported in humans on vacation/travel to Malaysia; sarcocysts were detected histologically in biopsy of muscles from some of these patients. These outbreaks of sarcocystosis-like illness in humans are summarized. Molecular epidemiological evidence suggests a new type of zoonosis linked to ingestion of food and water contaminated with “Sarcocystis nesbitti”. The life cycle of S. nesbitti remains unknown. Maccaque monkeys are thought to be its intermediate hosts and unknown species of snakes as definitive hosts. Evidence possibly linking S. nesbitti to human outbreaks or lack of it is reviewed.
Competitive RT-PCR Analysis of Brain Gene Expression During Inflammation and Disease

The developmental, functional, and pathological status of the central nervous system (CNS) requires regulation of several thousands of genes whose levels of expression vary from relatively abundant (>2%) to rare (<.001%). Although in most instances analysis of the expression patterns can be achieved by conventional RNA blot analysis, in many cases low levels of expression or limited amount of material require more sensitive methods, such as RT-PCR. In addition, in many instances the partially degraded nature of the materials precludes analyses dependent upon intact mRNA molecules. The advantages of RT-PCR methods and the use of specific internal competitive standards have allowed us to accurately measure multiple mRNA levels in samples derived from long-term glial cultures, isolated brain regions, and human autopsy material.
A Generative Joint, Additive, Sequential Model of Topics and Speech Acts in Patient-Doctor Communication

We develop a novel generative model of conversation that jointly captures both the topical content and the speech act type associated with each utterance. Our model expresses both token emission and state transition probabilities as log-linear functions of separate components corresponding to topics and speech acts (and their interactions). We apply this model to a dataset comprising annotated patient-physician visits and show that the proposed joint approach outperforms a baseline univariate model.
Asymmetric Consumer Search and Reference Prices

One suggested rationale for asymmetric price adjustments by firms is that firms are responding to asymmetric search behavior by consumers. Empirical evidence of asymmetric consumer search is limited due to the difficulties in observing search behavior, but theoretical models assume this asymmetric consumer search is generated by imperfect consumer information about the price distribution and/or heterogeneous costs of search. I demonstrate that asymmetric search occurs after a shift in the price distribution even when subjects know the price distribution and face a common cost of search, with consumers who face an upward shift in prices significantly more likely to search than those who face a downward shift in prices. Although the features of the search environment do not provide any theoretical predictions of asymmetric search in a standard framework, a model of reference-dependent preferences in which consumers view potential purchases as 'losses' or 'gains' relative to a reference price can generate predictions of asymmetric search that explains the response to price changes. Empirical results incorporating the previous purchase price as the reference price provide support for the reference price explanation.
Abstract 272: Targeted Activatable Cell-Penetrating Peptides Identify Atherosclerotic Plaques in Mice with Noninvasive Magnetic Resonance Imaging

Atherosclerotic plaque progression from stable lesions to advanced plaques that can spontaneously disrupt is promoted by numerous enzymes, including thrombin and extracellular matrix metalloproteases (MMPs). Assessing the activity of these enzymes in vivo by noninvasive MRI could be a valuable tool for the risk assessment of plaque disruption and a powerful method for monitoring the effectiveness of therapies. Novel thrombin- and MMP-targeted activatable cell-penetrating peptides (ACPPs) have a mechanism for activation and retention at sites of high enzymatic activity and show great promise for plaque detection due to incorporation of gadolinium (Gd), an MR active agent. In addition to the morphological information that is traditionally provided by MRI, both ACPPs also allow for a functional assessment of plaque. We hypothesized that these new targeted ACPPs would provide enhanced contrast at a smaller dosage and improve the sensitivity and specificity of plaque detection. The aorta of fat fed male ApoE knockout mice were imaged with a T1-weighted spin echo sequence before and after the administration of a substandard dose of non-targeted Gd-DTPA (2.5 μmol/kg, compared to the standard dose of 0.1-0.2 mol/kg). Administration of a comparable dose of thrombin- or MMP-targeted ACPP yielded a great increase in contrast around the aortic plaques (Figure 1). In conclusion, administration of the targeted ACPP achieved superior contrast and, therefore, demonstrates the potential to achieve high detection power of plaques with a much lower and safer dose of Gd. ![][1] [1]: /embed/graphic-1.gif
Measurement of Bound and Free Endotoxin by the Limulus Assay

SummaryThe Limulus assay was used to measure activities of naturally occurring and chemically extracted endotoxins and endotoxin fractions. Large amounts of both bound and free endotoxin were detected from gram-negative bacterial cells grown in either enriched or minimal media, and from resting cells. Following purification by phenol extraction, free endotoxin evidenced a similar level of activity to that of bound endotoxin. Lipid A and polysaccharide prepared by hydrolysis of endotoxin demonstrated reduced Limulus activity. However, R-strains from three species of gram-negative bacilli produced large amounts of free endotoxin. These results indicate that free endotoxin is part of the LPS that is readily released in a liquid environment, and probably is composed of lipid A and core material. In addition, a relatively constant amount of endotoxin remains bound on the cell surface, allowing an approximate quantitation of viable bacilli in fluids using the Limulus assay.
Abstract A18: Syndecan-1 is required for oncogenic Kras-driven PDAC tumorigenesis and maintenance

Although the universal presence of KRAS mutations and their critical role in human pancreatic ductal adenocarcinoma (PDAC) designates it as an ideal therapeutic target, oncogenic KRAS (KRAS*) is still regarded as ‘undruggable’ to date. Therefore, to identify therapeutic points of intervention, it is critical to understand the impact of KRAS*-mediated pathways on in vivo tumor pathogenesis. We have recently generated an inducible Kras G12D -driven (iKRAS*) mouse PDAC model and established a critical role for sustained KRAS* activity in tumor maintenance, providing a model to characterize pathways required for KRAS*-dependent tumorigenicity. Cell surface proteins are relatively accessible and can provide candidates for biomarker discovery, as well as be utilized as therapeutic targets. To characterize the KRAS*-specific organization of cell surface proteins toward the development of possible diagnostic or therapeutic tools, we conducted an unbiased surfaceome analysis of tumor cells in the presence and absence of KRAS* signaling using the iKRAS* mouse PDAC model. Syndecans (SDC), a family of heparin sulfate proteoglycans, were identified as candidates whose membrane expression is correlated with KRAS* activity. Specifically, Syndecan-1 (SDC1) expression was upregulated in response to KRAS* induction in acinar-ductal metaplasia (ADM) and early pancreatic intraepithelial neoplasia (PanIN), but not in cerulein-induced chronic pancreatitis. Moreover, SDC1 membrane expression was abolished upon KRAS* extinction, and our data indicated that the MAPK pathway, but not the PI3K pathway, drives KRAS*-mediated SDC1 surface localization. Supportive of our findings, it has been shown that SDC1 expression is increased in premalignant and malignant pancreatic lesions of primary human PDAC, as well as in various other KRAS*-driven pancreatic cancer mouse models. To further study the role of SDC1 in KRAS*-driven pancreatic cancers, we generated an SDC1-knockout mouse model and crossed with LSL-Kras G12D -PDAC models. Our preliminary data indicate that genetic ablation of SDC1 expression effectively suppressed KRAS*-driven PDAC initiation and progression. The mechanisms of KRAS*-mediated SDC1 membrane localization and its impact on PDAC initiation and progression will be further explored. Citation Format: Wantong Yao, Wei Wang, Ayumu Taguchi, Avnish Kapoor, Amin Momin, Hong Jiang, Johnathon Rose, Muge Celiktas, Angela Deem, Samir Hanash, Ronald DePinho, Haoqiang Ying, Giulio Draetta. Syndecan-1 is required for oncogenic Kras-driven PDAC tumorigenesis and maintenance. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A18.
Preclinical validation of a novel peptide radiotracer for detecting amyloidosis

83 Objectives Amyloidosis, a pathology characterized by the deposition of protein fibrils and heparan sulfate proteoglycans in the brain and other organs, is associated with Alzheimer’s disease, plasma cell cancers, and chronic inflammation. At present, clinical imaging of amyloid relies on radiolabeled small molecules for Aβ in Alzheimer’s patients and large proteins such as SAP for non-cerebral amyloid. Although effective, these tracers could benefit from enhanced amyloid affinity and tissue penetration, respectively. We have therefore developed as an alternative, a 31-mer peptide tracer that binds specifically and with high avidity to amyloid-associated proteoglycans. Methods The peptide, designated p31 was radiolabeled with I-125 and the amyloid-reactivity assessed in mice with severe peripheral systemic inflammation-associated (AA) amyloidosis by small animal SPECT imaging, tissue biodistribution measurements, and autoradiography. Results The 125I-p31 peptide cleared rapidly from amyloid-free mice ( Conclusions We have identified a novel peptide radiotracer that exhibits rapid, specific, and sustained binding to amyloid deposits in vivo. In addition, we have demonstrated binding of p31 to amyloid tissues from patients with Alzheimer’s disease (Aβ), plasma cell cancers (AL) and senile cardiac disease (ATTR). Thus, peptide p31 that targets heparin-like proteoglycans represents a novel biomarker for amyloid imaging. Research Support This work was supported a PHS grant R01DK079984 from the NIDDK
Design of Patient Testing Models for Cardiovascular Medical Device in Silico and In Vitro Assessment

Clinical evidence indicates that left ventricular assist device (LVAD) recipients present a diverse cohort of pathophysiology and cardiac functionality. The challenge of assuring device safety and proper performance in this patient set represents a challenge in both the range and resolution of the conditions. Furthermore, the cardiovascular systems of these individuals are highly susceptible to events that may trigger unsafe operating conditions for the LVAD: sudden postural change (e.g falling), drug induced tachycardia, etc. Developing appropriate computational design tools and reflective in vitro test system permits device designers to elucidate more liabilities in the design earlier in the development cycle. Conditions for a mock circulatory loop were sourced from clinical publications detailing the cardiovascular parameters determined for various patient classes and event sequences. The developed profiles for healthy adult, congestive heart failure adult, healthy geriatric, congestive heart failure geriatric, and healthy pediatric were designed. The profiles were developed from published clinical metrics and parameter estimations of PhysioBank data. How the profiles were constructed, as well as simulation and parameter estimation techniques will be discussed. As the profile of the patients receiving these devices diversifies, it becomes necessary to update the tools used in the V&V structure used to properly assess these new devices. The aforementioned mock circulatory loop, and accompanying computational model, deliver the combined V&V toolset needed to address this new range of questions on safety assurance for a widening scope of use for these devices.
Unbiased Quantized Congestion Notification for Scalable Server Fabrics

Ethernet is the predominant layer-2 networking technology in the datacenter, and it is evolving into an economical alternative for high-performance computing clusters. Ethernet traditionally drops packets in the event of congestion, but IEEE introduced lossless class services to enable the convergence of storage and IP networks. Losslessness is a simple, well-known concept, but its application in datacenters is hampered by the fear of ensuing saturation trees. In this article, the authors aim to accelerate the deployment of Quantized Congestion Notification (QCN). In particular, they first eliminate the intrinsic unfairness of QCN under typical fan-in scenarios by installing the congestion points at inputs, instead of at outputs as standard QCN does. They then demonstrate that QCN at input buffers cannot always discriminate between culprit and victim flows. To overcome this limitation, they propose a novel QCN-compatible marking scheme called "occupancy sampling." They have implemented these methods in a server-rack fabric with 640 100-Gigabit Ethernet ports.
Changes of Relevant Parameters of Proportional Assist Ventilation and Synchronized Intermittent Mandatory Ventilation in Young Rabbits with Severe Meconium Aspiration Syndrome

Objective To observe the changes in relevant parameters of proportional assist ventilation(PAV) and synchronized intermittent mandatory ventilation(SIMV)in young rabbits with severe meconium aspiration syndrome(MAS).Methods Thirty newborn Japanese big ear young rabbits(20-30 days old) were randomly divided into 4 groups:(1) PAV group(n=8),supported by PAV after meconium aspiration;(2) SIMV group(n=8),supported by SIMV after meconium aspiration;(3) MAS group(n=8),without ventilation but received continuous oxygen(500 mL·L-1) inhalation after meconium aspiration;(4)Control group(n=6),receiving continuous oxygen(500 mL·L-1) inhalation was received after saline aspiration.Related parameters recorded before(point 0) and 0.5 h after inhaled(point 0 ′),and at 1 h,2 h,3 h,4 h,5 h,6 h,7 h,8 hours of ventilation,including heart rate,breathing rate,tidal volume,peak airway pressure and mean airway pressure were investigated.The arterial blood gas was detected before and after 0.5 h irrigation,4 h and 8 h after ventilation,and the arterial/alveolar oxygen ratio(a/APO2) was calculated.Results Partial pressure of arterial carbon dioxide in PAV group and SIMV group at 4 h,8 h time points were in the normal range.The a/APO2 values in PAV group and SIMV group at 4 h,8 h were higher than those in point 0′(Pa0.05);There was no statistically significant difference in a/APO2 values at each point of time between the PAV group and SIMV group(Pa0.05).During the ventilation,peak airway pressure and mean airway pressure in SIMV group were higher than those in PAV group,the diffe-rences at each time point were statistically significant(Pa0.05).HR in SIMV group and MAS group were similar,the differences were not statistically significant at each time point(Pa0.05).Conclusions PAV can improve oxygenation state of lung in young rabbits with severe MAS effectively in a short term.Compared with SIMV,PAV has lower peak airway pressure and mean airway pressure when treated in young rabbits with severe MAS.PAV has little influence on heart rate of the young rabbits with severe MAS.
Effect of knockdown of Sigma-1 receptor on endoplasmic reticulum stress and podocyte injury

Objective:To explore the effect of knockdown of Sig-1R on endoplasmic reticulum stress and podocyte injury.Methods: siRNA vectors for silencing Sig-1R were constructed and transfected into mouse podocyte clones(MPC5),which were divided into normal control,negative control and interference groups.The mRNA and protein expressions of Sig-1R were detected by real-time PCR and Western blot,respectively.The apoptosis of podocytes was detected by nuclear staining using Hochest 33258.The protein expressions of nephrin,desmin,bcl-2,bax,caspase-3,8,9,12 were detected by Western blot.Results:The reducation of Sig-1R in mRNA and protein levels was detected when the podocytes were transfected with Sig-1R siRNA(P 0.05).The expression of nephrin decreased,while the expression of desmin increased significantly(P 0.05) compared to control.The apoptosis of podocyte was exhibited in the interference group.The expression of bcl-2 markedly decreased,while the expression of bax increased,and the ratio of bcl-2 to bax was less than 1/2.(P 0.05).The expression of active caspase-3 and caspase-12 increased significantly(P 0.05),while the expression of pro-caspase 9 decreased and pro caspase 8 had no change.Conclusion:The knockdown of Sig-1R can cause endoplasmic reticulum stress and podocyte injury.