cssi/SciSciGPT-SciSciNet huggingface dataset:
Towards the elimination of chromatography in protein purification: Expressing proteins engineered to purify themselves

The development of affinity-tag fusion technology in the mid-1980s provided a simple and convenient method for the purification of arbitrary recombinant proteins through genetic engineering. This method has recently been enhanced by the introduction of self-cleaving affinity tags based on engineered self-splicing inteins. The ability of these tags to release native product proteins from fusion precursors, in response to simple temperature or pH changes, has increased the appeal of this method for large-scale applications. We have recently developed two simple, cost-effective and scaleable protein purification technologies that exploit the self-cleaving reaction in novel, non-chromatographic contexts. In the first system, small granules of polyhydroxybutyrate (PHB) are produced in the expression host, which then act as an affinity carrier for the subsequently expressed target protein. The protein is tagged with a self-cleaving PHB-binding protein, allowing simple purification of the native product by simple granule washing and tag cleaving. In the second system, the target protein is tagged with a reversibly precipitating, self-cleaving elastin-like protein, allowing it to be separated from contaminants by simple cycles of precipitation and washing. The self-cleaving reaction again delivers a fully native, substantially purified product. Tests on several target proteins for both technologies show high purity and activity at reasonable yields, while initial economic analyses of these methods indicate a potential to dramatically reduce the cost of protein purification. Thus, the introduction of self-cleaving purification tags has enhanced an existing technology while enabling new technologies, and is likely to have a profound effect on the future of bioseparations.
Curriculum: Broad Brushstrokes or Paint-by-the Numbers?.

Abstract A renewed emphasis on standardized achievement tests has left teachers bewildered about what to teach and how to teach it. This article attempts to address that issue. Modified or enhanced mathematics instruction was the focus of this study based on two factors: national concerns over students’ achievement in mathematics and technology and the existence of an identified, national set of standards for mathematics instruction. Qualitative methodology was used to address research questions. Teachers involved in the study were trained in the different elements of curriculum modification practices and had one additional hour of orientation to the mathematics unit used in the study. Results of this study suggested that a modified or enhanced curriculum unit alone, with appropriate, escalated learning goals (Schunk, 1996) and authentic resources and products (Renzulli, 1977) can create substantial interest, motivation, and a perceived value in learning for students of all ability levels.
On the hydration and hydrolysis of carbon dioxide

The dissolution of carbon dioxide in water and the ensuing hydrolysis reactions are of profound importance for understanding the behavior and control of carbon in the terrestrial environment. The first X-ray absorption spectra of aqueous carbonate have been measured at three different pH values to characterize the evolution of electronic structure of carbonate, bicarbonate, carbonic acid and dissolved CO2. The corresponding carbon K-edge core-level spectra were calculated using a first-principles electronic structure approach which samples molecular dynamics trajectories. Measured and calculated spectra are in excellent agreement. Each species exhibits similar, but distinct, spectral features which are interpreted in terms of the relative C–O bond strengths, molecular configuration, and hydration strength.
Low temperature magnetothermoelectric effect and magnetoresistance in Te vapor annealed Bi2Te3.

The electrical properties of single crystals of p-type Bi2Te3 are shown to be tuned by annealing as-grown crystals in elemental Te vapor at temperatures in the range of 400?420??C. While as-grown nominally stoichiometric Bi2Te3 has p-type conductivity below room temperature, Te vapor annealed Bi2Te3 shows a cross over from p-?to n-type behavior. The temperature dependent resistivity of the Te annealed crystals shows a characteristic broad peak near 100?K. Applied magnetic fields give rise to a large low temperature magnetothermoelectric effect in the Te annealed samples and enhance the low temperature peak in the resistivity. Further, Te annealed Bi2Te3 shows a large positive magnetoresistance, ~ 200% at 2?K, and ~ 15% at room temperature. The annealing procedure described can be employed to optimize the properties of Bi2Te3 for study as a topological insulator.
Forskolin, phosphodiesterase inhibitors, and cyclic AMP analogs inhibit proliferation of cultured bovine aortic endothelial cells

The role of cyclic AMP on endothelial cell proliferation was investigated, since these cells can be exposed to high concentrations of physiological and pharmacological agents that alter cyclic AMP metabolism. Cloned bovine aortic endothelial cells were plated at 25,000 cells/35mm dish and grown for 5 days in the presence of phosphodiesterase (PDE) inhibitors, forskolin, or cyclic AMP analogs. The PDE inhibitors dipyridamole, ZK 62 711, isobutylmethylxanthine (IBMX) and theophylline inhibited cell growth in a concentration-dependent manner. Dipyridamole produced a 30% and a 50% inhibition at 5 microM and 12.5 microM, while higher concentrations were cytotoxic. At its therapeutic plasma concentration range (50-100 microM) theophylline inhibited cell proliferation by 15-25%, while IBMX and the highly specific cyclic AMP phosphodiesterase inhibitor, ZK 62 711 inhibited growth by 60-80% and 40-50%, respectively. Forskolin (5 microM) increased cyclic AMP levels and cyclic AMP-kinase activity ratios by 2.5-fold and 2-fold. In the absence of PDE inhibitors forskolin produced a 20% growth inhibition at 0.5 microM and a 60% inhibition at 10 microM. The forskolin dose-response curve was not altered by theophylline, but was shifted to the left by approximately 10-fold with dipyridamole and ZK 62 711 and 5-fold with IBMX. Forskolin (5 microM), by itself produced a 1.8-fold increase in cyclic AMP. In the presence of 5 microM theophylline, dipyridamole, IBMX, and ZK 62 711, cyclic AMP was increased by forskolin 2.0, 2.6, 3.5, and 6.6-fold, respectively. 8-Bromo cyclic AMP and dibutyryl cyclic AMP produced a 55% and 60% growth inhibition at 100 microM. The cyclic GMP analogs were less effective inhibitors of growth (15-30%). Our results demonstrate that cyclic AMP analogs and pharmacological agents that elevate intracellular cyclic AMP levels inhibit cell growth and suggest that cyclic AMP may be an important endogenous regulator of endothelial cell proliferation.
Divergent Wrench Faulting in the Belize Southern Lagoon: Implications for Tertiary Caribbean Plate Movements and Quaternary Reef Distribution

Analysis of 500 km of multichannel seismic reflection data in the Southern Lagoon of Belize reveals that its Tertiary structural evolution has been punctuated by two major transtensional episodes. First, left-lateral strike-slip motion parallel to the coast, together with a major component of extension, took place during the Paleocene, producing a series of southwest-northeast-trending en echelon normal faults, which created a topographic relief of ridges and troughs. Both the types of structures and their timing of formation are consistent with models that propose that Cuba swept past the eastern coast of Belize and the adjacent Yucatan peninsula, moving along a left-lateral transform boundary, until it collided with the Bahamas platform. The second tectonic event occurred during the Pliocene and/or later, revealing very recent activity along the North American-Caribbean left-lateral transform boundary. High-angle normal faults with a southwest-northeast orientation dominate the style. A comparison between the deep structure and the present bathymetry of the lagoon reveals that portions of the barrier platform and elongate to rhombohedral platform atolls, such as Laughing Bird Cay, are located over ancient structural highs, whereas bathymetric lows, such as the Victoria Channel, are long-lived troughs. This suggests that Quaternary reef foundations are deeper than previously thought, and that structure exercised a major control on sedimentation throughout the Tertiary evolution of the Southern Lagoon.
Full-Information Item Factor Analysis

A method of item factor analysis based on Thur stone's multiple-factor model and implemented by marginal maximum likelihood estimation and the EM algorithm is described. Statistical significance of suc cessive factors added to the model is tested by the likelihood ratio criterion. Provisions for effects of guessing on multiple-choice items, and for omitted and not-reached items, are included. Bayes constraints on the factor loadings are found to be necessary to suppress Heywood cases. Numerous applications to simulated and real data are presented to substantiate the accuracy and practical utility of the method. Index terms: Armed Services Vocational Aptitude Bat tery, Beta prior, EM algorithm, Item factor analysis, TESTFACT, Tetrachoric correlation.
Compressive distilled sensing: Sparse recovery using adaptivity in compressive measurements

The recently-proposed theory of distilled sensing establishes that adaptivity in sampling can dramatically improve the performance of sparse recovery in noisy settings. In particular, it is now known that adaptive point sampling enables the detection and/or support recovery of sparse signals that are otherwise too weak to be recovered using any method based on non-adaptive point sampling. In this paper the theory of distilled sensing is extended to highly-undersampled regimes, as in compressive sensing. A simple adaptive sampling-and-refinement procedure called compressive distilled sensing is proposed, where each step of the procedure utilizes information from previous observations to focus subsequent measurements into the proper signal subspace, resulting in a significant improvement in effective measurement SNR on the signal subspace. As a result, for the same budget of sensing resources, compressive distilled sensing can result in significantly improved error bounds compared to those for traditional compressive sensing.
tRNAHis 5-methylcytidine levels increase in response to several growth arrest conditions in Saccharomyces cerevisiae

tRNAs are highly modified, each with a unique set of modifications. Several reports suggest that tRNAs are hypomodified or, in some cases, hypermodified under different growth conditions and in certain cancers. We previously demonstrated that yeast strains depleted of tRNAHis guanylyltransferase accumulate uncharged tRNAHis lacking the G−1 residue and subsequently accumulate additional 5-methylcytidine (m5C) at residues C48 and C50 of tRNAHis, due to the activity of the m5C-methyltransferase Trm4. We show here that the increase in tRNAHis m5C levels does not require loss of Thg1, loss of G−1 of tRNAHis, or cell death but is associated with growth arrest following different stress conditions. We find substantially increased tRNAHis m5C levels after temperature-sensitive strains are grown at nonpermissive temperature, and after wild-type strains are grown to stationary phase, starved for required amino acids, or treated with rapamycin. We observe more modest accumulations of m5C in tRNAHis after starvation for glucose and after starvation for uracil. In virtually all cases examined, the additional m5C on tRNAHis occurs while cells are fully viable, and the increase is neither due to the GCN4 pathway, nor to increased Trm4 levels. Moreover, the increased m5C appears specific to tRNAHis, as tRNAVal(AAC) and tRNAGly(GCC) have much reduced additional m5C during these growth arrest conditions, although they also have C48 and C50 and are capable of having increased m5C levels. Thus, tRNAHis m5C levels are unusually responsive to yeast growth conditions, although the significance of this additional m5C remains unclear.
CXCR2 Macromolecular Complex in Pancreatic Cancer: A Potential Therapeutic Target in Tumor Growth

The signaling mediated by the chemokine receptor CXC chemokine receptor 2 (CXCR2) plays an important role in promoting the progression of many cancers, including pancreatic cancer, one of the most lethal human malignancies. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl termini, which might interact with potential PDZ scaffold/adaptor proteins. We have previously reported that CXCR2 PDZ motif-mediated protein interaction is an important regulator for neutrophil functions. Here, using a series of biochemical assays, we demonstrate that CXCR2 is physically coupled to its downstream effector phospholipase C-β3 (PLC-β3) that is mediated by PDZ scaffold protein Na+/H+ exchange regulatory factor 1 (NHERF1) into a macromolecular signaling complex both in vitro and in pancreatic cancer cells. We also observe that disrupting the CXCR2 complex, by gene delivery or peptide delivery of exogenous CXCR2 C-tail, significantly inhibits the biologic functions of pancreatic cancer cells (i.e., proliferation and invasion) in a PDZ motif-dependent manner. In addition, using a human pancreatic tumor xenograft model, we show that gene delivery of CXCR2 C-tail sequence (containing the PDZ motif) by adeno-associated virus type 2 viral vector potently suppresses human pancreatic tumor growth in immunodeficient mice. In summary, our results suggest the existence of a physical and functional coupling of CXCR2 and PLC-β3 mediated through NHERF1, forming a macromolecular complex that is critical for efficient and specific CXCR2 signaling in pancreatic cancer progression. Disrupting this CXCR2 complex could represent a novel and effective treatment strategy against pancreatic cancer.
Is procedure acquisition as unstable as it seems

Are students! mathematical procedures as unstable as they seem? Students often produce di!erent errors in response to the same kind of problems on di!erent testing occasions. This finding is puzzling. Past research has shown that students induce overly general procedures from worked-out examples during learning, which lead to a host of predictable errors on new problems. Do students create rule-based errors only to then switch between them at random? In this paper, we show that seemingly diverse errors on two di!erent testing episodes may result from the same underlying stable procedure and are part of the same error category. These findings suggest that students! errors are more stable on a category vs. on an individual level. The current study consists of teaching students addition in a new number system, called NewRoman, and analyzing students! solution strategies in detail. Implications for teaching are discussed. ! 2002 Elsevier Science (USA). All rights reserved.
Microbial Phototrophic, Heterotrophic, and Diazotrophic Activities Associated with Aggregates in the Permanent Ice Cover of Lake Bonney, Antarctica

The McMurdo Dry Valley lakes, Antarctica, one of the Earth's southernmost ecosystems containing liquid water, harbor some of the most environmentally extreme (cold, nutrient-deprived) conditions on the planet. Lake Bonney has a permanent ice cover that supports a unique microbial habitat, provided by soil particles blown onto the lake surface from the surrounding, ice-free valley floor. During continuous sunlight summers (Nov.–Feb.), the dark soil particles are heated by solar radiation and melt their way into the ice matrix. Layers and patches of aggregates and liquid water are formed. Aggregates contain a complex cyanobacterial–bacterial community, concurrently conducting photosynthesis (CO2 fixation), nitrogen (N2) fixation, decomposition, and biogeochemical zonation needed to complete essential nutrient cycles. Aggregate-associated CO2- and N2-fixation rates were low and confined to liquid water (i.e., no detectable activities in the ice phase). CO2 fixation was mediated by cyanobacteria; both cyanobacteria and eubacteria appeared responsible for N2 fixation. CO2 fixation was stimulated primarily by nitrogen (NO3 −), but also by phosphorus (PO4 3−). PO4 3− and iron (FeCl3+ EDTA) enrichment stimulated of N2 fixation. Microautoradiographic and physiological studies indicate a morphologically and metabolically diverse microbial community, exhibiting different cell-specific photosynthetic and heterotrophic activities. The microbial community is involved in physical (particle aggregation) and chemical (establishing redox gradients) modification of a nutrient- and organic matter-enriched microbial ``oasis,'' embedded in the desertlike (i.e., nutrient depleted) lake ice cover. Aggregate-associated production and nutrient cycling represent microbial self-sustenance in a microenvironment supporting ``life at the edge,'' as it is known on Earth.
An improved /spl pi//4-DQPSK compatible Feher's "/spl pi//4-FQPSK" nonlinearly amplified modulation

In this paper, a new modulation scheme suitable for digital satellite and land mobile communications, named /spl pi//4-FQPSK, is presented. It has the combined advantages of /spl pi//4-QPSK and FQPSK techniques by using Feher's patented techniques. Many researchers have shown that conventional /spl pi//4-DQPSK has significant spectral spreading in nonlinearly amplified channels. To reduce spreading we introduce an I/Q cross correlation baseband processor, which reduces the envelope fluctuation significantly. This makes the new modulation technique more suitable for nonlinear amplification, which is desirable for applications requiring high transmit efficiency such as digital satellite and land mobile communications. Unlike other power and spectrally efficient modulation systems, such as FQPSK-1, the /spl pi//4-FQPSK modulated signal can be detected noncoherently, due to the fact that there is no offset between the I and Q channel signals. The results of computer simulations demonstrate that /spl pi//4-FQPSK modulation technique is both power and spectrally efficient.
Phosphatidylinositol-4-phosphate 5-kinase activity is stimulated during temperature-induced morphogenesis in Candida albicans

Phosphoinositides are important lipid signalling molecules in eukaryotic cells. Phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) catalyses the production of phosphatidylinositol 4,5-bisphosphate (PIP2), which stimulates phospholipase D1 (PLD1) activity in mammalian and yeast cells. PLD1 catalyses the formation of phosphatidic acid (PA), which has been shown to activate PI4P5Ks in mammalian and Saccharomyces cerevisiae cells. In the present study, PI4P5K activity in the opportunistic pathogen Candida albicans was identified. A gene with significant sequence homology to the S. cerevisiae PI4P5K was cloned and designated MSS4. This gene was demonstrated to encode a functional PI4P5K by expression in S. cerevisiae. This enzyme was found to be membrane-associated and was stimulated by PA. Within the first 20 min after induction of polarized hyphal growth induced by a shift to elevated temperature, PI4P5K activity increased 2·5-fold. This stimulation was not observed when hyphae were induced by a combination of elevated temperature and serum. A lack of PLD1 activity resulted in the loss of induction of PI4P5K activity during the morphogenetic switch. Furthermore, the addition of propranolol attenuated the stimulation of PI4P5K activity during morphogenesis. These results suggest that PA derived from PLD1 activity stimulates C. albicans PI4P5K during the switch to the hyphal form under some conditions.
Assessment of Tropical Forest Degradation with Canopy Fractional Cover from Landsat ETM+ and IKONOS Imagery

Abstract Tropical forests are being subjected to a wide array of disturbances in addition to outright deforestation. Selective logging is one of the most common disturbances ongoing in the Amazon, which results in significant changes in forest structure and canopy integrity. Assessing forest canopy fractional cover (fc) is one way of measuring forest degradation caused by selective logging. In this study we applied a linear mixture model to a vegetation index domain to map canopy fractional cover in tropical forests in the Amazonian state of Mato Grosso, Brazil. The modified soil adjusted vegetation index (MSAVI) was selected as the optimal vegetation index in the model because it is most linearly related to green canopy abundance up to leaf area index = 4.0. In the canopy fc map derived from the Landsat Enhanced Thematic Mapper Plus (ETM+) image, the fc distribution ranged from 0 to 0.4 in clear-cut areas, higher than 0.8 in undisturbed forests, and a wider range of 0.3–1.0 in degraded forests. The fc ma...
Plasma Accumulation and Metabolism of Orally Administered Single Dose L-5-Hydroxytryptophan in Man

: Single oral doses of L-5-hydroxytryptophan (5-HTP) were administered in combination with L-aromatic amino acid decarboxylase inhibitors. The time courses of plasma concentrations of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and the concentrations of 5-HT in blood platelets were measured. Carbidopa enhanced the rise in plasma concentrations of 5-HTP 5–15 fold and counteracted the increase in plasma 5-HIAA levels induced by 5-HTP alone. A single dose of the decarboxylase inhibitor was equipotent to 14 days' pretreatment. Plasma or platelet concentrations of 5-HT failed to reflect the metabolism of 5-HTP. The ratio of 5-HTP to carbidopa influenced the systemic bioavailability of single dose administered 5-HTP indicating dose dependent absorption kinetics. Co-administration of L-dopa with 5-HTP and decarboxylase inhibitors had no effect on gastrointestinal absorption of 5-HTP in six parkinsonian patients.
The Use of Mechanical Property Measurements to Characterize Gels and Gelation Processes

There are a variety of gels (highly swollen solids) that are of considerable interest to polymer scientists, materials scientists, and ceramists. One type consists of typical organic polymers such as polyethylene or polystyrene, in networks which are formed by means of physical cross links, such as crystallites or physical aggregates. Such gels are thermoreversible in that liquefaction occurs upon heating. Another type consists of chain-like structures permanently bonded into covalent networks. These permanently branched and cross-linked chains can be either organic (phenol-formaldehyde resins, epoxies, etc.), or inorganic [silica (SiO2), titania (TiO2), zirconia (ZrO2), etc.] Both the organic and inorganic covalent types have been used to prepare aerogels, and the inorganic ones are now much used to prepare high-tech ceramics by the new sol-gel route. p]In the case of the thermoreversible, organic polymer gels, moduli can be measured as a function of concentration, temperature, and structural characteristics of the polymer (molecular weight, molecular weight distribution, and nature and degree of any chain branching). Such equilibrium results give information on the nature of the gels, including the influence of morphology, and the presence of dangling-chain irregularities. Measurements carried out as a function of time, for example, on polyethylene homopolymers and copolymers, can give information about their gelation kinetics. p]In the case of the ceramic materials, the evolution of the shear modulus with time is very useful in establishing induction times, rates of gelation, and aging effects. Correlation of such information with results of scattering studies can give much insight into the nature of the sol-gel process.
Experimental Melting of Pelagic Sediment, Constraints Relevant to Subduction

The experimental melting relations of pelagic red clay with water indicate a low temperature solidus, close to 650°C. This is significant as the red clay water solidus is lower than the solidus of gabbro with water, to depths of at least 140 km. Such a solidi configuration allows for melting of sediments, whilst gabbroic crust dehydrates, in moderate-temperature steady-state subduction regimes. This new experimental evidence lends support to (1) the sediment melting- gabbro dehydration hypothesis, recently proposed on independent geochemical criteria, and (2) may place relatively narrow limits on temperatures of the upper slab-mantle boundary, over a considerable depth interval, an apropos constraint for thermal modelling of steady-state subduction regimes.
Effects of structural marsh management on fishery species and other nekton before and during a spring drawdown

We sampled experimental research areas in the Barataria Basin of Louisiana, USA to examine the effects of structural marsh management on habitat use by small nekton (>100 mm Total Length or Carapace Width). The research areas consisted of two control (unmanaged) marshes and two impounded (managed) marshes; managed areas were surrounded by levees with water-control structures constructed by the U.S. Department of Interior, National Biological Survey. We sampled nekton with 1-m2 enclosure samplers in 1995 just as a drawdown was initiated (March) and after two months of drawdown (May); a drawdown is an active management technique in which water is allowed to flow out of, but not back into, the impoundment. Samples were collected randomly from all available habitat types (shallow open water, submerged aquatic vegetation (SAV), and intertidal marsh) in the managed and unmanaged areas. In March, the densities of resident taxa (e.g., Lucania parvac rainwater killifish and Palaemonetes paludosus riverine grass shrimp), which complete their life cycles within the estuary, were significantly greater in the managed areas compared to the unmanaged areas. The densities of most resident species were either similar in managed and control areas, or significantly greater in control areas during the drawdown (May). In contrast to residents species, the transient fishery species (e.g., Callinectes sapidus blue crab and Farfantepenaeus aztecus brown shrimp) reproduce outside of the marsh system and recruit to these areas as young. The densities of these transient species were significantly higher in unmanaged areas compared to managed areas during both sampling periods. We estimated standing crop (number or biomass of nekton per hectare of marsh area) by combining habitat densities with the area of different habitat types. The standing crops of transient species also were substantially greater in unmanaged than managed areas. We conclude that the restricted water exchange in marshes under structural marsh management diminishes recruitment and standing stocks of species that must migrate from coastal spawning sites to marsh nurseries. Even when water-control structures were open, the densities of these transient species were low inside managed areas. In contrast to the negative effect of management on transient species, the resident fish and crustacean populations seemed to flourish in the managed areas when a drawdown was not in effect. Following two months of a drawdown, however, the populations of residents appeared similar inside and outside managed areas. Increases in submerged aquatic vegetation (SAV) within ponds occurred outside the managed areas during the study period, but not inside managed areas. Because many resident species were closely associated with the SAV, the effect of management on SAV may have been responsible for the distribution patterns of resident species.
Laparoscopic nissen fundoplication for treating reflux in lung transplant recipients

Gastroesophageal reflux disease may contribute to pulmonary injury and the development of bronchiolitis obliterans syndrome in lung transplant patients. As a result, such individuals are increasingly likely to undergo corrective gastrointestinal surgery. The present study collected outcome data for 28 lung transplant patients with documented reflux who underwent an uncomplicated laparoscopic Nissen fundoplication at our institution. The results were compared to data from 63 nontransplant reflux patients who had undergone the procedure over the same time period. All Nissen fundoplications were conducted by the same surgeon. There were no intraoperative or perioperative deaths in either patient group. Operative parameters did not differ but the postoperative hospital stay was significantly greater for the lung transplant patients (P<0.05). Seven transplant patients (25%) were readmitted within 30 days compared to two readmissions (3.2%) in the reflux group. Five transplant patients (17.9%) have died, all from pulmonary complications; on average, death occurred 15.5 months after the Nissen surgery. There have been no deaths in the reflux group. These data indicate that laparoscopic Nissen fundoplication can be performed on lung transplant recipients to treat reflux. The average hospital stay is longer and there are more frequent readmissions in this population, but this does not appear to be due to any Nissen-related morbidity.
Maternal-Fetal In Vivo Imaging: A Combined PET and MRI Study

An understanding of how drugs are transferred between mother and fetus during the gestational period is an important medical issue of relevance to both therapeutic drugs and drugs of abuse. Though there are several in vitro and in vivo methods to examine this issue, all have limitations. Furthermore, ethical and safety considerations generally preclude such studies in pregnant humans. PET and appropriately labeled compounds have the ability to provide information on both maternal-fetal drug pharmacokinetics and pharmacodynamics. We present here a nonhuman primate animal model and the methodology for combining PET and MRI to identify fetal organs and to measure maternal and fetal isotope distribution using 18F-FDG and a whole-body imaging protocol to demonstrate proof-of-principle. Methods: One nonpregnant nonhuman primate was used for determination of the anesthesia protocol and MRI methods and 3 pregnant nonhuman primates (Macaques radiata) weighing 4.5–7 kg were used for the imaging study and anesthetized with propofol (160–300 μg/kg/min). Anatomic T2-weighted MR images were acquired on a 4-T MR instrument. Subsequently, whole-body PET images were acquired 35 min after injection of 18F-FDG, and standardized uptake values (SUVs) were calculated. Image processing and coregistration were performed using commercial software. Results: All animals underwent uneventful general anesthesia for a period of up to 7 h. Coregistration of PET and MR images allowed identification of fetal organs and demonstrated that 18F-FDG readily crosses the placenta and that 18F accumulates in both maternal and fetal brain, heart, and bladder. Brain SUVs averaged 1.95 ± 0.08 (mean ± SD) and 1.58 ± 0.11 for mothers and fetuses, respectively. Monkeys delivered healthy babies after a normal gestational term of 170 d following the PET/MRI study. Conclusion: The pregnant macaque in combination with PET and MRI technology allows the measurement of radioisotope distribution in maternal and fetal organs. This demonstrates the potential for noninvasively measuring the transfer of drugs across the placenta and for measuring the fetal drug distribution. It also opens up the possibility for studying binding and elimination as well as the effects of a drug on specific cellular elements and physiologic processes during the gestational period in a primate model.
Design of a smart, survivable sensor system for enhancing the safe and secure transportation of hazardous or high-value cargo on railroads

An application of smart sensor technology developed by Sandia National Laboratories for use in the safe and secure transportation of high value or hazardous materials is proposed for a railroad application. The Green Box would be capable of surviving most typical railroad accidents. In an accident, the system would send a distress signal notifying authorities of the location and condition of the cargo; permitting them to respond in the most effective manner. The concept proposes a strap-on sensor package. the Green Box, that could be attached to any railroad car or cargo container. Its primary purpose is to minimize the number, severity and consequences of accidents and to reduce losses due to theft. The system would also be capable of recognizing component failure conditions, notifying the operators and logging sensor data for use in directing preventative maintenance. The modular implementation, which facilitates system integration in a number of applications including the Advanced Train Control System (ACTS), is discussed. The methodology for determining the environmental specification for accident survivability is presented. A test plan for evaluating hardware performance in both normal operating and accident conditions is described. >
Community-Oriented Primary Care (COPC) and the Affordable Care Act An Opportunity to Meet the Demands of an Evolving Health Care System

Community-oriented primary care (COPC) is a model of health care delivery that tightly integrates primary care and public health. This model of care, applied around the globe, could be more widely adopted in the United States as clinical delivery systems respond to the growing demand for population health management, which has been driven largely by various provisions of the Affordable Care Act (ACA). For that purpose, there is need for changes in capacitating health professionals and changes in organizational structures that will address the needs and health priorities of the population, considering individual care management in the context of population health for a defined population. This article presents how the Affordable Care Act is an appropriate framework for COPC to succeed and the way forward to develop COPC through practical alternatives for the delivery of primary care within a population context.
Toxicity of sodium fluoroacetate and zinc phosphide wheat grain baits to Microtus guentheri and Meriones tristrami

Whole wheat grains impregnated with 0.02, 0.05 and 0.2% sodium fluoroacetate, and 2% zinc phosphide, were offered to series of single caged individuals of Microtus guentheri and Meriones tristrami. In most cases the sodium fluoroacetate treated baits were well accepted by both species. The acceptance of the zinc phosphide-treated bait was partial in all the series tested. The approximate LD50 ranges of sodium fluoroacetate are between 0.24 and 0.43 mg kg−1 for M. guentheri, and, perhaps, for the jirds too, and for zinc phosphide—between 32.6 and 58.8 mg kg−1 for M. tristrami, and a similar value, more or less, for M. guentheri.
Efficient directed test generation for validation of multicore architectures

Functional verification of multicore architectures is widely acknowledged as a major challenge. Directed tests are promising since a significantly smaller number of directed tests can achieve the same coverage goal compared to constrained-random tests. SAT-based bounded model checking is effective for automated generation of directed tests (counterexamples). While existing approaches focus on clause forwarding between different bounds to reduce the test generation time, this paper proposes a novel technique that exploits the structural similarity within the same bound as well as between different bounds. Our proposed technique enables the reuse of the knowledge learned from one core to the remaining cores in multicore architectures. The experimental results demonstrate that our approach can significantly (2–10 times) reduce overall test generation time compared to existing approaches.
Merging sequence stratigraphy and geomechanics for unconventional gas shales

The recent revelation of vast global quantities of potentially gas- (and oil-) productive shales has paved the way for rapid advancements in understanding their geological properties, many of which affect their geomechanical properties, and ultimately reservoir operations and performance. Because of shale's unique and very intricate geological, physical and mechanical properties at all scales (from nano- to macro-scale (Abousleiman et al., 2010) compared with sandstones and carbonates, the ad-jective “unconventional” has often been applied to their characterization. Although many shale characteristics are different than those of sandstones and carbonates, and require new technologies to measure them, other characteristics, mentioned below, are similar. As such, customized conventional methodologies and concepts can be applied to exploration and production of shale gas (and oil).
Joseph Alois Schumpeter 1883–1950

Introduction, 333. — I. Childhood, 1883–1901, 334. — II. University, 1901–06, 335. — III. Early academic career, 1906–18, 338. — IV. Foray into statesmanship and business, 1919–24, 344. — V. Academic life in Bonn and Harvard, 1925–50, 354. — VI. Schumpeter's contribution to economics, 360. — VII. Why is there no "Schumpeter school"? 370.
Computationally Designed Peptide Inhibitors of the Ubiquitin E3 Ligase SCFFbx4

A structure-based computational approach was used to rationally design peptide inhibitors that can target an E3 ligase (SCF(Fbx4) )-substrate (TRF1) interface and subsequent ubiquitylation. Characterization of the inhibitors demonstrates that our sequence-optimization protocol results in an increase in peptide-TRF1 affinity without compromising peptide-protein specificity.
Windings of spherically symmetric random walks via Brownian embedding

Abstract Let X 1 , X 2 , X 3 ,… be a sequence of i.i.d. R 2 -valued random variables with a spherically symmetric distribution. Let ( S n ; n ⩾0) be its sequence of partial sums and let ( φ ( n ); n ⩾0) be its winding sequence. Assuming only a mild moment condit show, via Brownian embedding, that 2 φ ( n )/log n converges in distribution to a standard hyperbolic secant distribution.
Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Empirical studies provide substantial evidence that having a family history of alcoholism increases the risk of developing alcohol dependence; however, some of this effect may be caused by nonspecific childhood socioeconomic adversity common in families with an alcohol-dependent parent. In this study, we examine joint effects of family history and childhood adversity within a sample of 509 men and 217 women over age 40. The measures analyzed were included in routine screening assessments for participants in various studies at the University of Michigan Alcohol Research Center. About 60% of the men and 45% of the women were alcohol-dependent. About 30% reported an alcoholic parent. Degree of family history affected drinking behavior for both men and women. There were also environmental effects on the same measures for both men and women. Childhood socioeconomic adversity was reported more frequently by participants with an alcoholic parent, but adversity effects were also shown for those with a negative family history. The risk of alcohol dependence was additively increased by a positive family history and childhood socioeconomic adversity. The environmental effects identified in this study are promising evidence for nonspecific factors that moderate family history risk for development of alcohol problems.
Human-pose estimation with neural-network realization

Previous studies on human-pose estimation rely on the design of factors to represent underlying probability distributions. However, designing factors is laborious and yet, the designed factors may not represent the underlying probability distributions. In this paper, we propose to use a neural network to automatically design factors in one of the existing models called the action-mixture model (AMM). Factors that are designed automatically by neural networks can be adapted to different situations. The semantic meaning of random variables in AMM can be transferred to a neural network, rendering the semantic meaning of hidden neurons transparent to users. The design process consists of two stages: structure identification and parameter learning. In the structure identification, we propose a bottom-up approach to build a neural network while preserving the structure of AMM. In the parameter learning, we propose a part-based approach to learn synaptic weights by decomposing a neural network into parts. Synaptic weights that have been learnt in one part can be used as initial weights for learning synaptic weights in another part. Based on the concept of distributed representation, the proposed two-stage, neural-network-based design process is used to design a scalable neural network to realize an AMM. Experimental results showed that the scalable neural network outperformed AMM and some existing works.
Risk Prediction With Procalcitonin and Clinical Rules in Community-Acquired Pneumonia: Answers to the July 2008 Journal Club Questions

Editor’s Note: You are reading answers to the fourth installment of Annals of Emergency Medicine Journal Club. The questions and the article they are about (Huang et al. Ann Emerg Med. 2008;52:48-58) were published in the July 2008 issue. We thank Dr. Huang and his colleagues for sharing additional data with us, which we used in answering question 4. Information about journal club can be found at http:// www.annemergmed.com/content/journalclub. Readers should recognize that these are suggested answers. We hope they are accurate; we know that they are not comprehensive. There are many other points that could be made about these questions or about the article in general. Questions are rated “novice,” ( ) “intermediate,” ( ) and “advanced” ( ) so that individuals planning a journal club can assign the right question to the right student. The “novice” rating does not imply that a novice should be able to spontaneously answer the question. “Novice” means we expect that someone with little background should be able to do a bit of reading, formulate an answer, and teach the material to others. Intermediate and advanced questions also will likely require some reading and research, and that reading will be sufficiently difficult that some background in clinical epidemiology will be helpful in understanding the reading and concepts. We are interested in receiving feedback about this feature. Please e-mail journalclub@acep.org with your comments.
Stress intensity factor calculation in sharp and beveled edge nozzle corners

Abstract This paper presents the work performed for the development of Stress Intensity Factor compendia for defects in nozzle corners. For that purpose, a large set Finite Element modeling were performed in order to cover the geometries, the defect sizes, the loading situations … encountered by large nuclear components. Then, based on that set of Finite Element modeling, an approximate solution relying on a fit of the stress field along the bisector line of the nozzle corner is proposed. This solution allows determining accurately the mean and maximum Stress Intensity Factor along the crack front for pressure loading and at the maximum of cold thermal shock loading. It is validated through a comparison to existing solutions or Finite Element modeling results.
Design and Characterization of a kind of C/C sealing material

A kind of C/C sealing material was designed and prepared.The material taking needled non-woven cloth as reform was sequentially densified by using CVD carbon,resin-based carbon and pitch-based carbon with intermediate heat treatment temperature of 2 500 ℃,and finally the material was modified by pore filling impermeability treatment.Comprehensive properties of the material were very good with density of 1.92 g/cm~3,opening pore percentage 0.06%,Shore hardness 77,the axial compressive strength 232 MPa,and the axial flexural strength 158 MPa.The material has been checked in the cold flow test and static firing test successfully.
A Deterministic Method for Haplotype Inference

Haplotypes are widely used in the analysis of relationship between genetics and diseases. Due to the cost of obtaining exact haplotype pairs, genotypes which contain the un-phased information corresponding to the haplotype pairs in the test subjects are used. Various haplotype inference algorithms have been proposed to resolve the un-phased information. In this paper, we propose a deterministic sequential Monte Carlo (DSMC)-based haplotype inference algorithm which allows for large datasets in terms of number of single nucleotide polymorphisms (SNP) and number of subjects, while providing similar or better performance for datasets under various conditions.
Magnetically-biased graphene-based hyperbolic metasurfaces

We explore the unusual electromagnetic response of magnetically-biased densely-packed graphene ribbons. Applying an effective medium approach, we show how the presence of a magnetostatic bias induces resonances on all components of the effective conductivity tensor, significantly enriching the features of the supported surface plasmons polaritons (SPPs). Specifically, we demonstrate magnetically-induced non-resonant topoloical transitions at terahertz (THz) frequencies, enabling planar canalization without the influence of large dissipative losses, and we predict the presence of weakly-confined transverse electric SPPs in a narrow band below resonance. Our findings may pave the way towards the development of planar, ultra-sensitive sensors, lenses, non-reciprocal components and imaging systems at THz.
The Spirit of Social Service (1920)

It is quite impossible for anyone who has been abroad recently not to tell of that experience. I was in Europe trying to find out as accurately as possible the condition of the children throughout several countries.
Valuing Evidence over Authority: The Impact of a Short Course for Middle-Level Students Exploring the Evidence for Evolution

Increasing both knowledge and acceptance of evolution are important outcomes of efforts to educate our students about the theory of evolution. Data were collected in the context of an 11-day short course focused on examining the evidence for evolution at a suburban STEM school in the Midwestern United States to answer the following research questions: (1) What effect did this course have on knowledge and acceptance of evolution? (2) How did cognitive and affective factors support growth in understanding of evolution in this evidence-centered educational intervention? This short course, comprising 21 students, focused on exploration-based activities allowing students themselves to collect evidence for evolution. We found significant gains in knowledge of microevolution and macroevolution, and found that both prior knowledge and acceptance of evolution were important in facilitating students’ conceptual growth.
Representations of temperature in the spinal cord

An animal is able to detect and interpret a wide range of temperature, while also being able to discriminate between two slightly different temperatures. Such dynamic range enables an animal not on...