cssi/SciSciGPT-SciSciNet huggingface dataset:
An analysis of percutaneous transhepatic cholangiograms

Percutaneous transhepatic cholangiograms (PTCs) of 74 cancer cases with obstruction of the biliary tree were reviewed and evaluated as to the location, degree of obstruction, and location of the obstructing elements ie, intra-luminal polypoid intrusions and diffuse infiltration. Special attention was given to the diagnostic value of the sign of an extrinsic compressing mass, a disputed entity. Every one of the above parameters, including extrinsic mass compression effect, proved to be worthwhile in arriving at a reasonable diagnosis. A system for coding obstructions to give maximum information in minimum space for large series of cases and to improve diagnostic accuracy of PTC in the single case is presented.
Evidence for facilitated lactate uptake in lizard skeletal muscle.

SUMMARY To understand more fully lactate metabolism in reptilian muscle, lactate uptake in lizard skeletal muscle was measured and its similarities to the monocarboxylate transport system found in mammals were examined. At 2 min, uptake rates of 15 mmol l –1 lactate into red iliofibularis (rIF) were 2.4- and 2.2-fold greater than white iliofibularis (wIF) and mouse soleus, respectively. α-Cyano-4-hydroxycinnamate (15 mmol l –1 ) caused little inhibition of uptake in wIF but caused a 42–54 % reduction in the uptake rate of lactate into rIF, suggesting that much of the lactate uptake by rIF is via protein-mediated transport. N -ethymaleimide (ETH) (10 mmol l –1 ) also caused a reduction in the rate of uptake, but measurements of adenylate and phosphocreatine concentrations show that ETH had serious effects on rIF and wIF and may not be appropriate for transport inhibition studies in reptiles. The higher net uptake rate by rIF than by wIF agrees with the fact that rIF shows much higher rates of lactate utilization and incorporation into glycogen than wIF. This study also suggests that lactate uptake by reptilian muscle is similar to that by mammalian muscle and that, evolutionarily, this transport system may be relatively conserved even in animals with very different patterns of lactate metabolism.
Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo

During gastrulation in the mouse, mesoderm is induced and patterned by secreted signaling molecules, giving rise first to primitive erythroblasts and vascular endothelial cells. We have demonstrated previously that development of these lineages requires a signal(s) secreted from the adjacent primitive endoderm. We now show that Indian hedgehog (Ihh) is a primitive endoderm-secreted signal that alone is sufficient to induce formation of hematopoietic and endothelial cells. Strikingly, as seen with primitive endoderm, Ihh can respecify prospective neural ectoderm (anterior epiblast) along hematopoietic and endothelial (posterior) lineages. Downstream targets of the hedgehog signaling pathway (the genes encoding patched, smoothened and Gli1) are upregulated in anterior epiblasts cultured in the presence of Ihh protein, as is Bmp4, which may mediate the effects of Ihh. Blocking Ihh function in primitive endoderm inhibits activation of hematopoiesis and vasculogenesis in the adjacent epiblast, suggesting that Ihh is an endogenous signal that plays a key role in the development of the earliest hemato-vascular system. To our knowledge, these are the earliest functions for a hedgehog protein in post-implantation development in the mouse embryo.
Measurement of insulin-like growth factor II by a specific radioreceptor assay in serum of normal individuals, patients with abnormal growth hormone secretion, and patients with tumor-associated hypoglycemia.

A radioreceptor assay for insulin-like growth factor II (IGF-II) is described in which [125I]IGF-II is bound by rat placental membranes. IGF-I and other insulin-related peptides have less than 1% of the potency of IGF-II in displacing [125I]-IGF-II. IGF-II is extracted from its serum binding protein with a simple acid-ethanol step. After neutralization with Tris base, the extract is introduced directly into the radioreceptor assay. Results are expressed in terms of a reference serum with an assigned potency of 1 U⁄ml. By this method, serum from normal adults, 20–69 yr of age, had a mean (±SE) IGF-II activity of 0.73 ± 0.03; higher concentrations were noted in adults more than 70 years of age (1.05 ± 0.05), in cord serum (1.55 ± 0.24), and in short children with normal GH secretion (0.88 ± 0.42). In hypopituitary dwarfism, serum IGF-II activity was reduced (0.50 ± 0.05), but in acromegaly, it was not increased (0.77 ± 0.06). In 10 of 14 serum samples from patients with tumor-related hypoglycemia, the IGF-I...
Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters

Abstract The dietary impact of specific phytosterols incorporated into phytosterol fatty acid esters has not been elucidated. Therefore, we tested the hypothesis that phytosterol esters containing different sterol moieties (sitosterol, sitostanol, or stigmasterol) but the same fatty acid moiety (stearic acid) produce different effects on cholesterol metabolism. Male Syrian hamsters were fed sitosterol, sitostanol, and stigmasterol stearate esters (25 g/kg diet) in an atherogenic diet containing cholesterol (1.2 g/kg) and coconut oil (80 g/kg). The phytosterol stearates produced no decrease in cholesterol absorption or plasma non–high-density lipoprotein cholesterol despite a reduction in liver free cholesterol in hamsters fed both sitosterol and sitostanol stearate diets. In addition, sitosterol stearate significantly increased fecal esterified and total neutral sterol excretion. Stigmasterol stearate did not differ from control in neutral sterol excretion, plasma lipids, or hepatic lipid concentration. Sitosterol stearate demonstrated the highest level of net intestinal hydrolysis, whereas sitostanol and stigmasterol stearate equivalently demonstrated the lowest. The cholesterol-lowering effect in liver—but not plasma—and the limited presence of fecal free sterols indicate that intact (unhydrolyzed) phytosterol stearates may impact cholesterol metabolism by mechanisms unrelated to the role of free phytosterols. The consumption of phytosterol esters at 2.5% of the diet elicited only modest impacts on cholesterol metabolism, although sitosterol stearate had a slightly greater therapeutic impact by lowering liver free cholesterol and increasing esterified and total neutral sterol fecal excretion, possibly due to a greater level of intestinal hydrolysis.
PhenoMan: phenotypic data exploration, selection, management and quality control for association studies of rare and common variants

Motivation: Next-generation sequencing and other high-throughput technology advances have promoted great interest in detecting associations between complex traits and genetic variants. Phenotype selection, quality control (QC) and control of confounders are crucial and can have a great impact on the ability to detect associations. Although there are programs to perform association analyses, e.g. PLINK and GenABEL, they cannot be used for comprehensive management and QC of phenotype data. To address this need PhenoMan was developed: to select individuals based on multiple phenotype criteria or population membership; control for missing covariate data; remove related individuals, duplicate samples and individuals with incorrect sex specification; recode primary traits and covariates; transform data; remove or winsorize outliers; select covariates for analysis; and create residuals. To ensure consistency and harmonization between analyses, a report is generated for every dataset. Summary statistics are also provided in graphical or text format. PhenoMan can be used for selection and manipulation of quantitative, disease and control data. Summary: Phenoman is freeware that provides approaches for efficient exploration and management of phenotype data. Proper QC of phenotypes before proceeding to the association analysis is critical to ensure control of type I and II errors, reliable effect estimates and consistent results between studies. PhenoMan is highly beneficial for the preparation of qualitative and quantitative trait data for association studies using new datasets as well as those obtained from public repositories. Availability and implementation: code.google.com/p/phenoman Contact: ude.mcb@laels
18.6-Year Earth Tide Regulates Geyser Activity

Over 40 years of records from Yellowstone National Park, Wyoming, show that the 18.6-year tidal component strongly regulates the frequencies of eruption of Grand and Steamboat geysers. The frequency of Grand Geyser increases with increasing tidal force and that of Steamboat Geyser decreases, which suggests that tidal dilatation is one factor affecting heat flow to a geyser.
Robot Localization Using RE and Inertial Sensors

A mobile robot must know its position in order to operate autonomously. The process of determining the robot's absolute position from sensor data is called robot localization. Sonar, inertial, RF, and laser sensors can all be used for navigation and localization purposes. These sensors can achieve good accuracy when operating in certain conditions. For example, sonar is useful when operating in a mapped environment containing known obstacles. Inertial sensors have trouble with drift, which is accentuated when moving continuously for long periods of time. By merging the results from multiple sensors, the accuracy over a wider range of conditions can be obtained. This work proposes a technique of merging heterogeneous signals from inertial and RF sensors. Since sensors have errors associated with their readings, the robot's state will be represented probabilistically. Based on the sensors used in this work, the robot's position, velocity, and acceleration will be estimated using a joint probability distribution function (PDF). At each time step, this PDF will be updated based on the RF readings and then updated again based on the readings from the inertial sensor. The proposed algorithm will be applied to simulation of an uncluttered, level environment. The accuracy of the localization algorithm is compared to the accuracies obtained by other localization algorithms. The results show better localization accuracy when using the RF and inertial sensors together.
An observational study of how young people search for online sexual health information.

Abstract Little is known about the quality of online sexual health information, how young people access the Internet to answer their sexual health questions, or an individual's ability to sort through myriad sources for accurate information. Objective: The purpose of this study was to determine how college students search for online sexual health information and whether they retrieve accurate answers to sexual health questions. Participants: In fall 2007, the authors recruited 34 first-year, first-semester undergraduates to participate in an observational research study, using Camtasia Studio. Results: Most students found accurate answers to the 12 sexual health questions posed. Finding local information and resources online proved more difficult than finding answers to general sexual health questions. Conclusions: The Internet has become the leading source for sexual health information. Based on their findings, the authors argue that young people must be educated about how Web search engine results are p...
Antarctic Miniature Lidar

Reports on a compact, low-power lidar that has been assembled, tested, and deployed at the Atmospheric Research Observatory (ARO) at the Amundsen-Scott South Pole Station since February 1996. The Antarctic Miniature Lidar uses commercially available, single-element semiconductor lasers (SDL-5430), a 20-cm Meade Schmidt-Cassegrain telescope, and single-photon counting (EG&G SPCM AQ-122). The authors present lidar measurements made during two polar nights, April 1996 through September 1996 and April 1997 through September 1997. The Antarctic Miniature Lidar has been designed to operate continuously during the polar night to detect the occurrence of polar stratospheric clouds which occur at altitudes of 12-27 km.
Pilot study of the pharmacokinetics of betel nut and betel quid biomarkers in saliva, urine, and hair of betel consumers

Approximately 600 million people worldwide practise the carcinogenic habit of betel nut/quid chewing. Carcinogenic N-nitroso compounds have been identified in saliva or urine of betel chewers and the betel alkaloid arecoline in hair from habitual betel quid chewers. However, the pharmacokinetic parameters of these compounds have been little explored. Assessment of betel use by biomarkers is urgently needed to evaluate the effectiveness of cessation programmes aimed at reducing betel consumption to decrease the burden of cancers in regions of high betel consumption. In the search for biomarkers of betel consumption, we measured by liquid chromatography-mass spectrometry (LC-MS) the appearance and disappearance of betel alkaloids (characteristic for betel nuts), N-nitroso compounds, and chavibetol (characteristic for Piper Betle leaves) in saliva (n=4), hair (n=2), and urine (n=1) of occasional betel nut/quid chewers. The betel alkaloids arecoline, guvacoline, guvacine, and arecaidine were detected in saliva of all four participants and peaked within the first 2 h post-chewing before returning to baseline levels after 8 h. Salivary chavibetol was detected in participants consuming Piper Betle leaves in their quid and peaked ~1 h post-chewing. Urinary arecoline, guvacoline, and arecaidine excretion paralleled saliva almost exactly while chavibetol glucuronide excretion paralleled salivary chavibetol. No betel nut related compounds were detected in the tested hair samples using various extraction methods. From these preliminary results, we conclude that betel exposure can only be followed on a short-term basis (≤8 h post-chewing) using the applied biomarkers from urine and saliva while the feasibility of using hair has yet to be validated. Copyright © 2015 John Wiley & Sons, Ltd.
Macroeconomic Policy, Redistribution and Democracy

A growing literature concludes that modern democracies have not adopted policies that benefit the majority to the extent predicted by social conflict theory. The most prominent reason is that globalization ties the hands of policymakers, making it hard for them to redistribute. Yet while progressive taxation has declined, we find that redistributive spending is higher in many democracies than would be expected by today's high levels of capital mobility. We also find that democratic countries that tend to appeal to the majority of the population, which we proxy for with the adoption of their own constitution after transition, use redistributive macroeconomic policies as an endrun around fiscal constraints. While popular democracies adopt flexible exchange rates that give them monetary autonomy, exhibit higher levels of inflationary finance, and incur more foreign debt, elite-biased democracies are more restrained. The latter also have smaller governments and engage in lower levels of redistributive spending.
What a Difference a Case Makes Or: What Goes into a Strong Supreme Court Majority

We undertake an analysis of majority size by issue area, Court composition, party of appointing President, and Martin-Quinn scores to gain leverage on what global factors, besides attitudinal belief, could be at play in a given case, and more specifically, what the trend of certain issues or Court compositions are in making larger majorities.
The Creative Imagination of the Sufi Mystic, Ibn ‘Arabi

The 12th–13thcentury mystic, Ibn 'Arabi, was known as “the Greatest Master” among the Sufis. His insights into dreams, visions and prophetic processes may prove enlightening to our own more secular age. The findings of Carl Jung parallel some of the revelations of the mystic, but Ibn 'Arabi goes farther than Jung into the Active Imagination as both conscious—willed—and spontaneous, autonomous process. Through surrender and annihilation in the Divine, the mystic opens himself to receive theophanies, resulting in a life lived perpetually in awareness of Divine Presence. Union with the Divine is the aim of the mystic and Ibn 'Arabi shows us a detailed account of how that life is experienced.
Functional imaging: PET.

Abstract Among various neuroimaging techniques used for the evaluation of children with intractable epilepsy, positron emission tomography (PET) employing various PET tracers plays a very important role, especially in localizing areas of focal cortical dysplasia. This is particularly important in infants, where incomplete myelination may limit the structural information provided by MRI. In children with tuberous sclerosis, PET can differentiate between epileptogenic and nonepileptogenic tubers, previously not thought to be possible with neuroimaging. PET may reveal cortical or subcortical abnormalities in various epilepsy syndromes, such as infantile spasms and Landau–Kleffner syndrome. Various other applications of PET have included the investigation of epileptic networks, secondary epileptic foci, dual pathology, and neuroinflammation. Finally, PET can also be used to evaluate various cognitive processes and their underlying neurological substrates and can help in addressing the issue of brain plasticity and reorganization, related to epilepsy.
Biological and Environmental Correlates of Aggressive Behavior

Aggressive behavior is influenced by the interplay of multiple genes that operate on brain biochemical pathways, neurotransmitters, and hormones, producing a certain psychological predisposition that, in contact with environmental risks within or outside the family, is conducive to antisocial aggressive behavior. This brief review of the scientific research shows that such behavior is the result of these predisposing, but not causal, factors. The importance of the individual's unique decisional capacity in such behavior is a question that requires further research.
MAD is the Best Possible Deterrence

It is futile to think that we can escape from deterrence based on mutually assured destruction, whether through disarmament schemes or by conjuring up elaborate war-fighting scenarios. Like the bomb, deterrence is a fact of life.
Love and Equity: The Social Doctrine of Origen of Alexandria:

There has been a renewed interest, in the academy and in the church, in the teaching of the Church Fathers on social and economic questions, and in particular on the proper distribution of material...
Abstract A13: Identification of evolutionarily conserved genetic interactions in DNA mismatch repair

The DNA mismatch repair (MMR) system is responsible for correcting base substitution and insertion-deletion mutations (IDLs) generated during erroneous replication in bacteria, yeast and mammals. MMR complexes also recognize damaged-base mispairs resulting from environmental exposure to DNA damaging agents. The loss of MMR causes a “mutator” phenotype, resulting in the genome-wide accumulation of mutations, and is the underlying cause for Hereditary Non-polyposis Colorectal Cancer / Lynch Syndrome (HNPCC/LS) and a significant proportion of sporadic colorectal cancer (CRC). MMR-deficient tumors also display resistance to DNA damaging agents and, as a consequence, are resistant to a variety of commonly chemotherapeutic agents. Thus, the development of novel therapeutic strategies that more efficiently target MMR-deficient cancer cells would be highly desirable. A promising new direction to identify potential targets for anticancer treatment is the harnessing of synthetic lethality. Here, we have identified conserved synthetic lethal / sick genetic interactions (GIs) for MMR factors between two distant yeast species, S. pombe and S. cerevisiae. We have confirmed several of these negative GIs in mammalian cells, indicating that they are evolutionarily conserved. Specifically, we have identified a negative genetic relationship between Msh2, a major MMR component mutated in colorectal cancer, and Senp6 protease, which regulates the SUMOylation of a range of genome maintenance proteins. Our findings suggest that Senp6 is a promising new target for the treatment of MMR-deficient CRCs. Citation Format: Elena Tosti, Joseph A. Katakowski, Sonja Schaetzlein, Hyun-Soo Kim, Colm J. Ryan, Michael Shales, Assen Roguev, Nevan J. Krogan, Deborah Palliser, Michael-Christopher Keogh, Winfried Edelmann. Identification of evolutionarily conserved genetic interactions in DNA mismatch repair. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Synthetic Lethal Approaches to Cancer Vulnerabilities; May 17-20, 2013; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(5 Suppl):Abstract nr A13.
Rapid Microwave-Assisted Grafting of Layered Perovskites with n-Alcohols.

Dion–Jacobson layered niobates have been extensively researched in recent years because of a variety of useful properties such as dielectric behavior, proton conduction, and solid acid catalysis. The behavior of these materials is strongly dependent on the elemental composition and, more specifically, the interlayer surface environment. A novel method of partial grafting of n-alcohols into the interlayer of HSr2Nb3O10 with approximately 40% conversion has been developed using microwave irradiation to generate high temperatures. This method has reduced the grafting reaction time by more than 97% while maintaining conversion rates consistent with previous methods.
Directional reversals enable Myxococcus xanthus cells to produce collective one-dimensional streams during fruiting-body formation

The formation of a collectively moving group benefits individuals within a population in a variety of ways. The surface-dwelling bacterium Myxococcus xanthus forms dynamic collective groups both to feed on prey and to aggregate during times of starvation. The latter behaviour, termed fruiting-body formation, involves a complex, coordinated series of density changes that ultimately lead to three-dimensional aggregates comprising hundreds of thousands of cells and spores. How a loose, two-dimensional sheet of motile cells produces a fixed aggregate has remained a mystery as current models of aggregation are either inconsistent with experimental data or ultimately predict unstable structures that do not remain fixed in space. Here, we use high-resolution microscopy and computer vision software to spatio-temporally track the motion of thousands of individuals during the initial stages of fruiting-body formation. We find that cells undergo a phase transition from exploratory flocking, in which unstable cell groups move rapidly and coherently over long distances, to a reversal-mediated localization into one-dimensional growing streams that are inherently stable in space. These observations identify a new phase of active collective behaviour and answer a long-standing open question in Myxococcus development by describing how motile cell groups can remain statistically fixed in a spatial location.
Towards Exploring Data-Intensive Scientific Applications at Extreme Scales through Systems and Simulations

The state-of-the-art storage architecture of high-performance computing systems was designed decades ago, and with today's scale and level of concurrency, it is showing significant limitations. Our recent work proposed a new architecture to address the I/O bottleneck of the conventional wisdom, and the system prototype (FusionFS) demonstrated its effectiveness on up to 16 K nodes—the scale on par with today's largest supercomputers. The main objective of this paper is to investigate FusionFS's scalability towards exascale. Exascale computers are predicted to emerge by 2018, comprising millions of cores and billions of threads. We built an event-driven simulator (FusionSim) according to the FusionFS architecture, and validated it with FusionFS's traces. FusionSim introduced less than 4 percent error between its simulation results and FusionFS traces. With FusionSim we simulated workloads on up to two million nodes and find out almost linear scalability of I/O performance; results justified FusionFS's viability for exascale systems. In addition to the simulation work, this paper extends the FusionFS system prototype in the following perspectives: (1) the fault tolerance of file metadata is supported, (2) the limitations of the current system design is discussed, and (3) a more thorough performance evaluation is conducted, such as N-to-1 metadata write, system efficiency, and more platforms such as Amazon Cloud.
Pubertal Timing and Substance Abuse Treatment Outcomes: An Analysis of Early Menarche on Substance Use Patterns

ABSTRACTThis article examines the influence of pubertal timing on substance use patterns, specifically the relationship between onset of menarche and onset of substance use and substance abuse treatment outcomes. Findings show a significant relationship between pubertal timing and age of onset of substance use and age of onset of substance use and substance use severity at intake into treatment. The article concludes with a call for further research into the possible relationship between pubertal timing and treatment outcomes as well as effective gender-specific interventions for prevention and treatment of substance abuse among adolescent girls.
Predicting hand function in older adults: evaluations of grip strength, arm curl strength, and manual dexterity

Hand function is critical for independence in activities of daily living for older adults. The purpose of this study was to examine how grip strength, arm curl strength, and manual dexterous coordination contributed to time-based versus self-report assessment of hand function in community-dwelling older adults. Adults aged ≥60 years without low vision or neurological disorders were recruited. Purdue Pegboard Test, Jamar hand dynamometer, 30-second arm curl test, Jebsen-Taylor Hand Function Test, and the Late-Life Function and Disability Instrument were administered to assess manual dexterous coordination, grip strength, arm curl strength, time-based hand function, and self-report of hand function, respectively. Eighty-four adults (mean age = 72 years) completed the study. Hierarchical multiple regressions show that older adults with better arm curl strength (β = −.25, p < .01) and manual dexterous coordination (β = −.52, p < .01) performed better on the time-based hand function test. In comparison, older adults with better grip strength (β = .40, p < .01), arm curl strength (β = .23, p < .05), and manual dexterous coordination (β = .23, p < .05) were associated with better self-report of upper extremity function. The relationship between grip strength and hand function may be test-specific. Grip strength becomes a significant factor when the test requires grip strength to successfully complete the test tasks. Arm curl strength independently contributed to hand function in both time-based and self-report assessments, indicating that strength of extrinsic muscles of the hand are essential for hand function.
Diabetes mellitus is a coronary heart disease risk equivalent for peripheral vascular disease

Background Diabetes mellitus (diabetes) is associated with significantly increased risk of peripheral vascular disease. Diabetes is classified as a coronary heart disease (CHD) risk equivalent, but it is unknown whether diabetes is a CHD risk equivalent for peripheral vascular disease. The objective was to evaluate the odds of peripheral arterial disease (PAD) or carotid artery stenosis (CAS) among participants with diabetes, CHD, or both, compared with participants without diabetes or CHD, in a nationwide vascular screening database. We hypothesized that diabetes and CHD would confer similar odds of PAD and CAS. Methods A cross-sectional analysis of all eligible Life Line Screening Inc participants age 30 to 90 years with ankle brachial indices for PAD (ankle brachial index Results Diabetes and CHD were present in 372,330 (10.7%) and 182,760 (5.8%) of participants, respectively; PAD and CAS were present in 155,000 (4.4%) and 130,347 (3.7%) of participants. After multivariable adjustment, PAD odds were 1.56 (95% CI 1.54-1.59) and 1.69 (95% CI 1.65-1.73) for participants with diabetes or CHD, respectively. Participants with both diabetes and CHD had 2.75-fold increased odds of PAD (95% CI 2.66-2.85). Findings were similar for CAS; compared with no diabetes or CHD, CAS odds increased for participants with diabetes alone (1.53, 95% CI 1.50-1.56), CHD alone (1.72, 95% CI 1.68-1.76), and both diabetes and CHD (2.57, 95% CI 2.49-2.66). Findings were consistent for women and men. Conclusion In a large database of more than 3.5 million self-referred participants, diabetes was a CHD risk equivalent for PAD and CAS, and participants with comorbid diabetes and CHD had an especially robust association with PAD and CAS. Counseling regarding screening and prevention of peripheral vascular disease may be useful for patients with diabetes.
In Utero Cocaine Exposure and Infant Behavior

The effects on neurobehavior in 20 infants with prenatal exposure to cocaine, alcohol, marijuana, and cigarettes, compared to 17 infants exposed to alcohol and/or marijuana and cigarettes without cocaine and 20 drug-free infants, were assessed using the Neonatal Intensive Care Unit Network Neurobehavioral Scale at Brown University School of Medicine, Women and Infants Hospital, Providence, RI.
T394A Mutation at the μ Opioid Receptor Blocks Opioid Tolerance and Increases Vulnerability to Heroin Self-Administration in Mice

The etiology and pathophysiology underlying opioid tolerance and dependence are still unknown. Because mu opioid receptor (MOR) plays an essential role in opioid action, many vulnerability-related studies have focused on single nucleotide polymorphisms of MOR, particularly on A118G. In this study, we found that a single-point mutation at the MOR T394 phosphorylation site could be another important susceptive factor in the development of opioid tolerance and dependence in mice. T394A mutation, in which a threonine at 394 was replaced by an alanine, did not alter agonist binding to MOR and opioid analgesia, but resulted in loss of etorphine-induced MOR internalization in spinal dorsal horn neurons and opioid analgesic tolerance induced by either morphine or etorphine. In addition, this mutation also caused an increase in intravenous heroin self-administration and in nucleus accumbens dopamine response to heroin. These findings suggest that T394 phosphorylation following MOR activation causes MOR internalization and desensitization, which subsequently contributes to the development of tolerance in both opioid analgesia and opioid reward. Accordingly, T394A mutation blocks opioid tolerance and leads to an increase in brain dopamine response to opioids and in opioid-taking behavior. Thus, the T394 may serve as a new drug target for modulating opioid tolerance and the development of opioid abuse and addiction. SIGNIFICANCE STATEMENT The mechanisms underlying opioid tolerance and susceptibility to opioid addiction remain unclear. The present studies demonstrate that a single-point mutation at the T394 phosphorylation site in the C-terminal of mu opioid receptor (MOR) results in loss of opioid tolerance and enhanced vulnerability to heroin self-administration. These findings suggest that modulation of the MOR-T394 phosphorylation or dephosphorylation status may have therapeutic potential in management of pain, opioid tolerance, and opioid abuse and addiction. Accordingly, MOR-T394 mutation or polymorphisms could be a risk factor in developing opioid abuse and addiction and therefore be used as a new biomarker in prediction and prevention of opioid abuse and addiction.
Microfabrication of anodes for use in microbial fuel cells

The recent discovery that metal-reducing bacteria are also capable of reducing solid electrodes has enabled the study of microbial fuel cells or sensors utilizing bacteria as catalysts. However, use of large (~50 cm2) electrodes, cut from variable surface area graphite materials, restricts the throughput, precision, and resolution of microbial fuel cell research. Therefore, we are investigating technology for miniaturization and better characterization of the microbial fuel cell. First, a scalable technique for constructing membrane-electrode assemblies (MEAs) was developed, via the hot-pressing of carbon-based anodes to proton exchange membranes and Pt/C-based cathodes. Anaerobic glass and polycarbonate chambers able to accept these MEAs were tested with Geobacter metallireducens as the microbial catalyst at the anode and a solution of potassium ferricyanide at the cathode. These cells were found to completely oxidize substrates, converting organic compounds into electricity. To replace the anodes in these chambers, we combined a series of designs enabling silicon to act as both a porous membrane and substrate for microscale conductive parts, for current collection (W. Smyrl et. al, AlChE J. 48, 1071) as well as for high-resolution voltammetric characterization (E.Yoon et. al, Jpn J. Appl. Phys. 39, 7159). Nitride-coated silicon wafers ([100] P-type) were photolithographically patterned with a series of windows ranging from 2 mum2 to 800 mum2 in size, and etched completely through using both wet and dry etching techniques. Using metal evaporation, one side of this porous silicon was patterned with a 1 nm thick Ti/Au layer, providing conductive sites for microbial reduction that could be controlled for active surface area. Silicon-based anodes were tested as components in MEA-based fuel cells. Depending on the pattern of Au deposition and pore profile, anodes had characterized active surface areas ranging from a few square microns to three orders of magnitude higher. Based on attachment and current production characteristics of G. metallireducens with these microfabricated anodes, designs were selected for refinement and miniaturization, with the goal of producing arrays of porous anodes, (approximately 0.25 cm2), for growth and testing of multiple electrode-reducing cultures, as well as flat anodes (on the order of 5 mum2) suitable for parallel, high-resolution electrochemical characterization of respiration at the microscale
Grain Based Modeling of Stress Induced Copper Migration for 3D-IC Interwafer Vias

We discuss our grain-continuum approach to modeling stress-driven grain boundary migration in polycrystalline Cu films, assuming that migration is due to differences in strain energies. We focus on thermally induced stresses and compute those using Comsol Multiphysics. To account for grain structure in polycrystalline films, the anisotropic elastic constants of single crystal Cu are used for each grain, after aligning them with each grain's orientation. Local grain boundary velocities are calculated based on the differences in strain energy across grain boundaries. The computed velocities are then used to update the level sets that represent the grain boundaries using the PLENTE software. Simple and more complicated grain structures are studied as part of a larger effort to understand the effects of thermally induced stresses in 3D-IC inter-wafer vias.
Abstract 807: Parental radiation elicits increased intestinal tumorigenesis in the F1 generation of APCMin/+ and APC1638N/+ mice

The risk of colorectal cancer (CRC) has been reported to increase with radiation exposures as well as with a positive family history. Radiation exposure has also been implicated in inducing heritable changes in parental germline cells and thus increasing risk of cancer in the offspring. However, effects of parental radiation exposure on trans-generational colorectal carcinogenesis in offspring have not been explored yet. We employed two well-characterized mouse models (APCMin/+ and APC1638N/+) of human CRC to determine trans-generational effects of low dose radiation on colorectal carcinogenesis. Male APCMin/+ and APC1638N/+, and female C57BL/6J mice were exposed to whole body 25 cGy of x rays. Mating was initiated two days after radiation exposure, F1 offspring were genotyped, and male and female APCMin/+ and APC1638N/+ were grouped and housed separately. APCMin/+ mice were euthanized 150 days after birth, APC1638N/+ mice after 210 days, and tumor frequency and size in intestine and colon were noted. Significantly increased intestinal tumor frequency and increased numbers of larger tumors were observed in F1 mice of irradiated parents relative to F1 mice of sham-irradiated parents. Greater trans-generational tumorigenic effects of radiation were observed in male offspring relative to female offspring. In conclusion, here we present an early report for the first time that low dose radiation exposure has a trans-generational effect on intestinal tumorigenesis with potential implications for radiation exposure-related human health consequences. Citation Format: Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Ziling Fan, Albert J. Fornace, Kamal Datta. Parental radiation elicits increased intestinal tumorigenesis in the F1 generation of APCMin/+ and APC1638N/+ mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 807. doi:10.1158/1538-7445.AM2015-807
Measuring Change: Pitfalls in Research Design

In this issue, the Research Report, entitled "Results of an Online Refresher Course to Build Braille Transcription Skills in Professionals and Volunteers," by Herzberg and Rosenblum, uses pretest and posttest scores on a 20-item multiple-choice test to compare the participants' knowledge before and after taking an online course. In this Statistical Sidebar, I will discuss the realm of pretest-posttest measures as a way to assess change. This approach is used frequently in scholarly research, given the logic that measuring performance or knowledge before some sort of training and then measuring it again after the instruction should provide an idea of the effectiveness of the intervention. The method of using pretest-posttest measures, however, can be subject to a number of subtle flaws. As in any experimental design, random assignment of participants to experimental and control groups makes the study stronger (for more information on this topic, please see the Statistical Sidebar, "Control Groups and Experimental Groups: It Is All in the Numbers," which was published in the January-February 2015 issue). Unfortunately, it is not always possible to use random assignment, and even when participants are randomly placed in experimental and control groups, the pretest-posttest design is subject to threats to internal validity. The particular type of pretest-posttest design used in this report was a "one group pre-posttest design," in which there was no control group and, therefore, no random assignment of participants. Although the pretest-posttest model is quite common, this type of research design is open to threats of history, maturation, testing, and instrumentation. Since time passes between the pretest and posttest measures, participants experience other events in the interim. This threat of "history" means that participants might be influenced by factors outside of the study that affect their performance on the posttest. If enough time passes between the pretest and posttest, then the threat of "maturation" might be a factor, in which biological changes in the participants might influence posttest scores. There is also the possibility that, since the pretest and posttest are measuring the same knowledge or skill, the act of taking the pretest elevates knowledge or performance, meaning that the training is not fully responsible for the measured change. If the exact same assessment is used for both the pretest and the posttest, when participants take the posttest, they have already answered the questions or performed the skills it requires, which might artificially inflate performance on the posttest. …
Actions of Butyrylcholinesterase Against Cocaine

Abstract Accelerating cocaine metabolism producing physiologically and biologically inactive metabolites is recognized as an ideal approach to therapeutic treatment of cocaine overdose and addiction. Butyrylcholinesterase (BChE) in plasma is the principal cocaine-metabolizing enzyme in humans. Unfortunately, catalytic efficiency of wild-type BChE against naturally occurring, biologically active (–)-cocaine is too low to be effective. Unique computational enzyme redesign approaches have been developed and employed to rationally design and discover a variety of BChE mutants, known as cocaine hydrolases (CocHs), with at least 1000-fold improved catalytic efficiency compared to the wild-type BChE against (–)-cocaine. Preclinical studies revealed that these CocHs are promising for treatment of cocaine overdose and addiction. The first CocH (i.e., CocH1) is currently under clinical trial phase II for cocaine addiction treatment. Compared to CocH1, more recently designed and discovered CocHs have not only significantly higher catalytic efficiency against (–)-cocaine and its toxic metabolites, but also significantly longer biological half-lives.
DANCE/MOVEMENT THERAPY: A HOLISTIC APPROACH TO WORKING WITH THE ELDERLY

The purpose of this paper is to examine dance/movement therapy as a holistic approach for working with the elderly. The premise is that dance/movement therapy can play a vital role in the prevention and treatment of illness with the elderly and act as a motivating force for maximizing lifelong growth potential. Therapeutic approaches to physically. emotionally. and intellectudly disabled elderly are discussed. The paper concludes that dance/movement therapy with the elderly can be an enlightening experience which can inspire the therapist and clients to face life and death with love and energy.
Integrated Multiscale Biomaterials Experiment and Modeling

The integration of modeling and experimentation is an integral component of all engineering design. Developing the technologies to achieve this represents a critical challenge in biomaterials because of the hierarchical structures that comprise them and the spectra of timescales upon which they operate. Progress in integrating modeling and experiment in biomaterials represents progress towards harnessing them for engineering application. We present here a summary of the state of the art, and outlooks for the field as a whole.
The Plasma Protamine Paracoagulation Test: Clinical and Laboratory Evaluation

The plasma protamine paracoagulation test has been evaluated as performed on citrated plasma at 37 C. with protamine sulfate in a final concentration of 0.09%. Instructions to prevent false positive results have been summarized. The test detected nascent clotting in vitro , fibrin monomer added to plasma in a final concentration of 0.05 mg. per ml., and early fibrin degradation products. During a period of 3 years, every patient we encountered with evidence of intravascular clotting by other criteria had an abnormal plasma protamine test result. Thus, a negative test constitutes strong evidence against a diagnosis of intravascular clotting. Patients were discovered with the combination of a clinical disorder predisposing to intravascular clotting, no or minimal abnormalities of other coagulation studies, and an abnormal plasma protamine test. The significance of this combination is discussed. The plasma protamine paracoagulation test should be included in the screening evaluation of the patient with suspected intravascular clotting.
Imaging the Postoperative Knee Meniscus: An Evidence-Based Review.

OBJECTIVE. Unenhanced MRI, indirect MR arthrography, direct MR arthrography, and CT arthrography are each currently used to evaluate patients with recurrent knee pain after meniscus surgery. The pu...
Action Research as a Guiding Principle in an Educational Curriculum: The Lincoln University Master’s Program in Human Services

Kurt Lewin is the social scientist who most exemplifies the fundamental orientation of the program in graduate Human Services at Lincoln University. Although Lewin made remarkable strides toward the conceptual formalization of the social sciences, he was also able to poignantly demonstrate the utility of social science knowledge in understanding and solving real-life social problems (Lewin, 1948, 1951).
The "fuzzy logic" of the death-inducing signaling complex in lymphocytes.

Receptors belonging to the tumor necrosis factor receptor family have long been thought to play an important role in the regulation of immunity. Although this family is composed of a large number of surface receptors that potentiate myriad functions in vivo, a subset is known to directly convey apoptotic signals. One such molecule belonging to this subset is CD95. Ligation of CD95 instigates the formation of a complex known as the “death-inducing signaling complex” or DISC, which is composed of molecules including FADD (Fas associated with death domain) and RIP (receptor-interacting kinase), as well as procaspases-8 and -10, and a caspase-8-like molecule that lacks proteolytic activity called c-FLIP. Although the DISC was initially thought to serve an exclusively proapoptotic role, humans and mice with defects in various components of this complex demonstrate a variety of developmental and hematopoietic defects that are not apparently due to aberrant apoptosis. These findings paint a far more complex picture of the numerous components of the DISC, and provide evidence that these complexes serve nonapoptotic functions. Herein, we summarize the experimental evidence challenging the notion that the DISC imparts an exclusively apoptotic function and provide hypotheses to account for these alternative roles. Rather than operating as a binary system, we propose that the DISCs formed around various DRs transduce signals leading to a variety of cellular fates.
Domain Specificity of Genetic Programming Based Automated Synthesis: A Case Study with Synthesis of Mechanical Vibration Absorbers

Genetic programming has proved its potential for automated synthesis of a variety of engineering systems such as electrical, control, and mechanical systems. Given any of these application domains, a set of generic GP functions can be developed for its synthesis. In this chapter, however, we illustrate that while a generic GP system can often be used to prove a concept, realistic or industrial automated synthesis often requires domain-specific GP configuration, especially of the GP function sets. As a case study, it is shown how the open-ended topology search capability of GP readily exploits “loopholes” in a generic bond-graph-based GP function set and evolves high-performance but unrealistic mechanical vibration absorbers, even though the bond graphs would be readily implementable in, for example, the electrical domain. The preliminary attempt to constrain evolved topologies to only those that would be readily implementable in the mechanical domain was not sufficiently restrictive.
PHENIX results on elliptic and triangular flow from the small-system geometry scan at 200 GeV

Abstract Using the extraordinary versatility of RHIC in selecting different colliding species, the PHENIX experiment has collected data in p +Al, p +Au, d +Au, and 3 He+Au collisions at 200 GeV center-of-mass energy and conducted a comprehensive set of anisotropic flow measurements. These geometry-controlled experiments provide a unique testing ground for theoretical models that produce azimuthal particle correlations based on initial- and/or final-state effects. A complete set of triangular anisotropies of inclusive charged particles and final results on identified pion and proton v 2 ( p T ) are shown. The mass-ordered splitting in v 2 ( p T ) provides information about the role of early-stage collective flow and late-stage hadronic rescattering. Detailed model comparisons with all observables are discussed.