cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4431: NFATc1 silencing increases sensitivity of pancreatic cancer cells to phosphosulindac

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. Current chemotherapeutic agents have limited efficacy and play a minor role in its treatment. We previously determined that the novel agent phosphosulindac (P-S) significantly prevents colon cancer and have now extended our studies into pancreatic cancer. Microarray data demonstrated a 5-fold increase in the gene expression of Nuclear Factor of Activated T-cells (NFAT) in MIA PaCa-2 cells after 2 h of treatment with P-S. NFATc1 and NFATc2 isoforms have been shown to be up-regulated in pancreatic cancer. To determine the role NFATc1 played in response to treatment with our compound, we developed a NFATc1 shRNA model in BxPC-3 and GFP positive MIA PaCa-2 cells, and a NFATc1 overexpression model in GFP labeled MIA PaCa-2 cells. Knockdown of NFATc1 expression by shRNA was confirmed by western blot and qRT-PCR. A 2-fold decrease in IC 50 of P-S was observed in NFATc1 shRNA cells. In contrast, overexpression of NFATc1 increased the IC 50 of P-S by 1.2-fold. The ability of our compound to reduce cell viability more potently in NFATc1 shRNA cells prompted us to assess the effect of the protein on tumor growth in a MIA PaCa-2 xenograft. 5-6 week old female BALB/c nude mice were subcutaneously injected with NFATc1 wt, knock-down, and overexpression GFP labeled MIA PaCa-2 cells. Animals were treated for 5 weeks, euthanized and tumor volume assessed. We observed a 50% reduction in tumor volume in NFATc1 wt, 63% reduction in NFATC1 knock-down, and a 26% reduction in NFATc1 overexpression xenograft. NFATc1 localization is indicative of its activity, with nuclear localization being the active form. We assessed OCT-embedded sections of our xenograft tissue to determine the localization of NFATc1 in GFP labeled tumor cells. Confocal microscopy data showed that in comparison to control, P-S treated tissue demonstrated decreased nuclear localization of the protein, indicating that P-S may suppress the activation of NFATc1. We observed a similar trend in NFATc1 knock-down and overexpression tissue, though our compound demonstrated a greater effect on tumor reduction in NFATc1 knock-down mice. We conclude that P-S is a potentially important agent for the treatment of pancreatic cancer and that our compound may play a role in NFATc1 localization and activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4431. doi:1538-7445.AM2012-4431
High-Resolution Leed Study of Intermixing of Fe Films on Au(001) Surface

Ultrathin ferromagnetic Fe films have been grown on an Au(00l) surface. Using the angular profile measurements of High-Resolution LEED (HRLEED), we show the inho-mogeneities at the interface due to atomic place exchange between Fe and Au atoms can drastically change the angular intensity distributions of diffraction beams. The contributions from the inhomogeneities on the surface can be properly decoupled from the total angular intensity distributions. Through the energy dependent angular profile analysis of diffraction beams, we have quantitatively determined the degree of inhomogeneous atomic intermixing at elevated annealing temperatures.
Predictors of Outcome in Bladder Cancer

Tumor stage and grade have largely been responsible for directing treatment algorithms in bladder cancer. However, the considerable heterogeneity of tumor biology in bladder cancer is incompletely characterized by stage and grade alone, and recent efforts to improve predictive models in bladder cancer may significantly improve accuracy and calibration. This article addresses how current nomograms and risk tables may be best used to individualize bladder cancer management.
Antagonism of chlorpromazine byβ-melanocyte stimulating hormone (β-MSH)

Une preparation hautement purifiee de l'hormone melanophoretiqueβ-MSH inhibe les effets de la chlorpromazine au niveau de la moelle spinale.
Use of somatosensory evoked potentials in infants and children.

Somatosensory evoked potentials (SEPs) are a useful, reliable means of assessing function of the somatosensory system. Factors of complex maturational changes of the CNS, such as synaptogenesis and myelination, as well as body growth, complicate interpretation of SEPs. Understanding of these factors enhances clinical interpretation in infants and children.
Ageing and ocular surface immunity

The prevalence of ocular surface immunopathologies is enhanced in the elderly. This increased prevalence has been attributed to age-related dysregulation of innate and adaptive immune system responses. Age-related changes in ocular surface immunity have similar and distinct characteristics to those changes seen in other mucosal tissues. This mini review provides a brief outline of key findings in the field of ocular ageing, draws comparisons with other mucosal tissues and, finally, discusses age-related changes in the context of immunopathogenesis of infectious keratitis and dry eye disease, two of the most common inflammatory disorders of the ocular surface.
Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T.

PURPOSE To evaluate the feasibility of using a clinical magnetic resonance (MR) system and MR spectroscopy (MRS) to measure glucose concentration changes in the human hypothalamus, a structure central to whole-body glucose regulation. SUBJECTS AND METHODS A time series of MR spectra (semi-LASER, TE = 28 msec), localized to the bilateral hypothalamus (∼1.6 ml) were obtained at 3T in six healthy subjects at baseline (euglycemia) and during a ∼65-70-minute-long hyperglycemic clamp in 11-minute blocks with interleaved T1 FLASH images to retrospectively assess head motion, and track changes in cerebrospinal fluid (CSF) partial volume. The LCModel was used to quantify the sum of glucose and taurine concentrations, [Glc+Tau], along with their associated Cramer-Rao lower bounds (CRLB). RESULTS Spectral quality allowed quantification of [Glc+Tau] (sum reported due to high negative correlation between these metabolites) with CRLB <25% in 35/36 timepoints during hyperglycemia. Increased [Glc+Tau] was observed with hyperglycemia in all subjects, but most reliably in those with plasma glucose targets ≥300 mg/dl. For these subjects, [Glc+Tau]baseline (n = 4) was 1.5 (±0.3, SD) mM, and increased to 4.5 (±1.1) mM (n = 16) for timepoints acquired ≥25 minutes after onset of the clamp, with 15/16 timepoints having no overlap of 95% confidence intervals (CIs) between baseline and hyperglycemia. Preliminary analysis revealed a linear (1:5) relationship between hypothalamus-blood glucose concentrations. CONCLUSION It is feasible to measure glucose concentration changes in the human hypothalamus using a standard 3T scanner and a short-echo semi-LASER sequence by utilizing retrospective motion tracking, CSF correction, predetermined quality acceptance criteria, and hyperglycemic blood glucose levels ≥300 mg/dl. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017;45:681-691.
The Generalization of Implicit Racial Bias to Young Black Boys: Automatic Stereotyping or Automatic Prejudice?

Although children typically elicit benevolence and care from adults, these protections are not afforded equally to children of all races: Implicit racial biases commonly directed toward Black adults appear to generalize to young Black children. In two experiments, we tested whether such effects reflect biases in semantic associations (i.e., automatic stereotyping), evaluative associations (i.e., automatic prejudice), or both. White participants categorized objects and words that varied in racial stereotypicality and valence after brief presentations of male faces that varied in race (Black, White) and age (adults, children). Results revealed consistent support for a general-stereotyping account: Seeing Black male faces, regardless of age, facilitated the identification of both negative and positive stereotypic stimuli. We also found some support for a prejudice account, as these same faces facilitated the identification of negative stimuli more generally. Process-dissociation-procedure analyses further re...
Metasemantics: New Essays on the Foundations of Meaning, edited by Alexis Burgess and Brett Sherman

Metasemantics collects thirteen original papers on foundational issues in the philosophy of language, plus a substantial introductory essay by the editors and a brief preface by Scott Soames. Both ...
Retrospective Integration of Research Conducted on a Multi-Section Educational Psychology Course over a Fifteen-Year Period

This article integrates a series of studies conducted over a 15-year period in a multi-section educational course taught by the same supervising professor and his GTAs . The purpose of each study was to determine whether particular interventions or student characteristics affected performance levels in the course. Over the extended period of research, approximately 6000 undergraduate students, with 25 to 55 students in each of more than 200 sections, participated in a variety of research projects related to student performance in the course. The principal research themes addressed were (1) critical thinking, (2) additional cognitive measures (e.g., initial course knowledge, generic vocabulary), (3) class participation, (4) in-class writing activities, and (5) cooperative learning.
The Art of Analytical Benchmarking

The most primitive numerical method of solving the radiative transfer equation forms the basis of an algorithm to generate high quality numerical solutions. We apply convergence acceleration to the discrete ordinates balance equation derived from a diamond difference approximation. Wynn-epsilon and Romberg accelerations then rearrange low order solutions to produce a high order solution. Published semianalytical benchmarks from the C.E. Siewert portfolio establish the credibility of the new converged discrete ordinates method (CDOM).
Disruptive fixation: school reform and the pitfalls of techno-idealism

Much has been written about the increasingly active role of philanthropic foundations in K-12 school reform (Hess 2005; Ball 2008; Kovacs 2011; Ravitch 2011; Reckhow 2012; Lipman 2014; Reckhow and ...
Representation and Diversity, Advocacy, and Nonprofit Arts Organizations:

In recent years, arts and culture nonprofits have sought to make themselves more relevant to community issues by engaging in advocacy. Based on survey data drawn from a national sample of arts nonp...
Examining whites’ anti-black attitudes after Obama’s presidency

ABSTRACTWe develop and test competing theoretical expectations about the level and effects of white prejudice against blacks in the aftermath of America’s first black presidency. Using both cross-s...
Patient Factors: Resistance, Coping, Affect, and Styles

Patient characteristics such as resistance, coping behaviors, emotional reactions, and individual and cultural stylistic differences impact genetic counseling processes and outcomes. In order to provide effective services, genetic counselors must be able to recognize and address patient factors as appropriate. This chapter describes a few of the ways in which patients differ stylistically, discusses some of the patient emotional issues genetic counselors encounter, and considers how patients may resist, defend, and cope when they feel threatened. Specifically, resistance is defined, and responses for addressing patient resistance are identified; and defense mechanisms are differentiated from other types of coping behaviors. Next the chapter describes selected types of patient emotions (e.g., grief, anger, anxiety, guilt, and shame) and patient stylistic differences (e.g., emotional and intellectual styles, religion/spirituality dimensions) and their impact on the genetic counseling relationship. Specific strategies are presented to help students increase their sensitivity to patients’ individual and cultural differences and learn to more effectively tailor their counseling approaches, accordingly. Structured activities and written exercises provide practice in recognizing and addressing patient factors in genetic counseling.
Louv, Richard. (2005). Last child in the woods: saving our children from nature-deficit disorder

(2006). Louv, Richard. (2005). Last child in the woods: saving our children from nature-deficit disorder. SCHOLE: A Journal of Leisure Studies and Recreation Education: Vol. 21, No. 1, pp. 136-137.
The Structure of Perception and Action

In general approach, the present book reverses the traditional strategy discussed in Chapter 1 of treating perception and action separately, because I begin with the evidence for shared perception-production units, which play a role in both perception and action. By taking up action next, the book also reverses the traditional strategy of giving priority to perception. I attempt first to specify a detailed set of theoretical processes for sequencing and timing the production of speech and other skilled behaviors involving shared perception-production components. I then examine how these shared perception-production components give rise to perception, and I develop a theory with applications to classical perceptual problems such as categorical perception, perceptual invariance, the nature of perceptual errors, perception of the distal stimulus, perception of sequential inputs, and the problem of ambiguity in perception.
Left Ventricular Atrophy in Pulmonary Arterial Hypertension: A Sinister Dexter Conundrum∗

In response to external demands, the myocardium undergoes adaptive changes. This process has been termed cardiac plasticity, and changes at the macroscopic and cellular levels under various environmental conditions have been documented [(1)][1]. The most basic response to increased volume or
Growth Factor Regulation of Osteogenesis

Osteogenesis, the creation of bone, underlies all skeletal development and repair. It encompasses the differentiation of cells along specific developmental pathways and the production by these cells of the matrix required to construct, or to reconstruct, bone. The control of this process is, to a large extent, the responsibility of cell signaling molecules that include hormones, growth factors, and cytokines. This chapter reviews some of the factors that participate in regulating the creation of bone at the cellular level.
Chapter 4 – Specialty Fiber Optic Cables

Fiber optic cables are used for a wide range of applications, including enhanced distance, optical amplification and attenuation, and dispersion and polarization management. This chapter describes the most common types of fiber-optic cables and their uses. The chapter also reviews the manufacturing process for the common graded index single-mode and multimode fiber types. It is noted that it is possible to package multiple optic fibers into a single unibody cable or into a ribbon or zipcord structure. Bundles of fibers whose ends are bound together, ground, and polished can form flexible light pipes. Fibers can also be bundled in such a way that there is no fixed relationship between the location of an input fiber and an output fiber, the principle purpose of such structures so obtained is to conduct light from one location to another. A coherent bundle of single-mode fiber is capable of conducting a high-quality image, in case when the bundle is made highly flexible, such fiber arrays have many applications in remote vision systems and are used in fiber optic endoscopes for medical applications.
A common deliberative process underlies model-based planning and patient intertemporal choice

Humans and animals consistently forego, or 9discount9 future rewards in favor of more proximal, but less valuable, options. This behavior is often thought of in terms of a failure of 9self-control9, a lack of inhibition when considering the possibility of immediate gratification. However, rather than overweighting the near-term reward, the same behavior can result from failing to properly consider the far-off reward. The capacity to plan for future gains is a core construct in Reinforcement Learning (RL), known as 9model-based9 planning. Both discounting and model-based planning have been shown to track everyday behaviors from diet to exercise habits to drug abuse. Here, we show that these two capacities are related via a common mechanism -- people who are more likely to deliberate about future reward in an intertemporal choice task, as indicated by the time they spend considering the choice, are also more likely to make multi-step plans for reward in a sequential reinforcement learning task. In contrast, the degree to which people9s intertemporal choices were driven by a more automatic bias did not correspond to their planning tendency, and neither did the more standard measure of discounting behavior. These results suggest that the standard behavioral economic measure of discounting is more fruitfully understood by decomposing it into constituent parts, and that only one of these parts corresponds to the sort of multi-step thinking needed to make plans for the future.
Novel endoscopic modalities for closure of perforations, leaks, and fistula in the gastrointestinal tract

Abstract Full-thickness gastrointestinal (GI) defects remain a daunting clinical problem in modern medicine. They vary in size, location in the GI tract, etiology, and chronicity. While traditionally managed with surgical techniques or medical management, technological advancements have created a third management option (therapeutic endoscopy), which often result in definitive defect closure. With the advent of these endoscopic therapies, many centers have moved to endoscopic management as first-line therapy of such defects. Optimal endoscopic management may require multimodal, multisession therapy, which occurs in the setting of a multispecialty management team. This manuscript reviews the use of endoscopic clips (both through-the-scope and over-the-scope), endolumenal stents, endoscopic suturing, endolumenal vacuum devices, and other emerging technologies in the managing of full-thickness GI defects. We examine the optimal clinical application of each modality and review their limitations.
Urodynamic Mechanisms Underlying Overactive Bladder Symptoms in Patients With Parkinson Disease.

Purpose To assess the urodynamic findings in patients with Parkinson disease (PD) with overactive bladder symptoms. Methods We performed a retrospective chart review of all PD patients who were seen in an outpatient clinic for lower urinary tract symptoms (LUTS) between 2010 and 2017 in a single-institution. Only patients who complained of overactive bladder (OAB) symptoms and underwent a video-urodynamic study for these symptoms were included. We excluded patients with neurological disorders other than PD and patients with voiding LUTS but without OAB symptoms. Results We included 42 patients (29 men, 13 women, 74.5±8.1 years old). Seven patients (16.7%) had a postvoid residual (PVR) bladder volume >100 mL and only one reported incomplete bladder emptying. Detrusor overactivity (DO) was found in all 42 patients (100%) and was terminal in 19 (45.2%) and phasic in 22 patients (52.4%). Eighteen patients had detrusor underactivity (DU) (42.3%). Later age of PD diagnosis was the only parameter associated with DU (P=0.02). Patients with bladder outlet obstruction (BOO) were younger than patients without BOO (70.1 years vs. 76.5 years, P=0.004), had later first sensation of bladder filling (173.5 mL vs. 120.3 mL, P=0.02) and first involuntary detrusor contraction (226.4 mL vs. 130.4 mL, P=0.009). Conclusion DO is almost universal in all patients with PD complaining of OAB symptoms (97.1%). However, a significant percentage of patients also had BOO (36.8%), DU (47%), and increased PVR (16.7%) indicating that neurogenic DO may not be the only cause of OAB symptoms in PD patients.
Alternative Datasets for Identification of Earth Science Events and Data

Alternative, or non-traditional, data sources can be used to generate datasets which can in turn be analyzed for temporal, spatial and climatological patterns. Events and case studies inferred from the analysis of these patterns can be used by the remote sensing community to more effectively search for Earth observation data. In this paper, we present a new alternative Earth science dataset created from the National Weather Service’s Area Forecast Discussion (AFD) documents. We then present an exploratory methodology for identifying interesting climatological patterns within the AFD data and a corresponding motivating example as to how these data and patterns can be used to search for relevant events or case studies.
Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility

Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage. Epigenetic changes that are associated with lineage restriction during regeneration remain underexplored. We produce epigenome maps, including DNA methylation and chromatin accessibility, as well as transcriptomes, of osteoblasts and other cells in uninjured and regenerating fins. This effort reveals regeneration as a process of highly dynamic and orchestrated transcriptomic and chromatin accessibility changes, coupled with stably maintained lineage-specific DNA methylation. The epigenetic signatures also reveal many novel regeneration-specific enhancers, which are experimentally validated. Regulatory networks important for regeneration are constructed through integrative analysis of the epigenome map, and a knockout of a predicted upstream regulator disrupts normal regeneration, validating our prediction. Our study shows that lineage-specific DNA methylation signatures are stably maintained during regeneration, and regeneration enhancers are preset as hypomethylated before injury. In contrast, chromatin accessibility is dynamically changed during regeneration. Many enhancers driving regeneration gene expression as well as upstream regulators of regeneration are identified and validated through integrative epigenome analysis.
Technologies and Standardization in Research on Extracellular Vesicles

Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component of a variety of physiological and pathological processes. Potential applications of EVs in novel diagnostic and therapeutic strategies have brought increasing attention. However, EV research remains highly challenging due to the inherently complex biogenesis of EVs and their vast heterogeneity in size, composition, and origin. There is a need for the establishment of standardized methods that address EV heterogeneity and sources of pre-analytical and analytical variability in EV studies. Here, we review technologies developed for EV isolation and characterization and discuss paths toward standardization in EV research.
Three Simple Hands-On Soil Exercises Extension Professionals Can Incorporate into Natural Sciences Curriculum

The importance of healthy soil and of conveying the importance of soils starts by conveying a few basic concepts of soil science cannot be overstated. This article provides three hands-on exercises Extension professionals can add to natural resources or Master Gardener education curricula. These natural sciences exercises are easy to prepare for the instructor and accurately reflect behavior of soil in situ. These exercises are designed for classroom use, but they can be used concurrently with field training. These exercises are appropriate for both youth and adult audiences.
Civilly Criminalizing Homelessness

The criminalization of homelessness refers to the enactment and enforcement of laws and policies that punish un-sheltered people for surviving in public space, even when those individuals have no reasonable alternative. The constitutional and civil rights issues stemming from criminally charging un-sheltered people for public survival are controversial but clear. But cities often skirt legal challenges to criminalization by avoiding criminal charges and pursuing other means to punish homelessness. Many cities “civilly criminalize homelessness” through civil enforcement, which extends from infractions or fines to “invisible persecution,” such as the persistent policing and surveilling of un-sheltered people. So while courts, legislatures, and advocates commonly focus on criminal charges, these punishments are just the tip of the criminalization iceberg: civil enforcement is arguably more extensive, pervasive, and damaging; however, courts and legislatures do not protect people experiencing homelessness from civil criminalization. This Article argues for greater attention to the devastating impact of civil punishments, drawing from other critiques that expose how civil tools punish poor and vulnerable people. It also examines how punishment operates outside of both criminal charges and civil sanctions, severely penalizing un-sheltered people and requiring reform.
Pygmalion in the genes? On the potentially negative impacts of polygenic scores for educational attainment

Polygenic scores for educational attainment and related variables, such as IQ and “mathematical ability” are now readily available via direct-to-consumer genetic testing companies. Some researchers are even proposing the use of genetic tests in educational settings via “precision education,” in which individualized student education plans would be tailored to polygenic scores. The potential psychosocial impacts of polygenic scores for traits and outcomes relevant to education, however, have not been assessed. In online experiments, we asked participants to imagine hypothetical situations in which they or their classmates had recently received polygenic scores for educational attainment. Participants prompted to answer multi-choice questions as though they had received their own low-percentile score, compared to a control condition, scored significantly lower on measures of self-esteem and of self-perceived competence, academic efficacy, and educational potential. Similarly, those asked to evaluate a hypothetical classmate as though the classmate had received a low-percentile score attributed significantly lower academic efficacy and educational potential, compared to a control condition. Through possible mechanisms of stigma and self-fulfilling prophecies, our results highlight the potential psychosocial harms of exposure to low-percentile polygenic scores for educational attainment.
Effect of Opioids on Sleep

Opioid medications are often used to manage pain in the intensive care unit. Opioids, whether used as recreational drugs or for hospital patient pain management, impact the quality of sleep. Nurses should assess for pain and provide appropriate amounts of pain medications, while minimizing opioid use once the patient can tolerate non-narcotic medications. Nurses should assess the intensive care unit patient's sleep quality and be mindful of the effect that opioid medications have on sleep quality.
P13 An international comparison of mobile phone subscribership and motor vehicle crash injuries

Abstract Background Mobile phone use while driving has been associated with a substantially higher likelihood of motor vehicle crash risk and is the focus of numerous traffic safety policies and initiatives worldwide in recent years. Although prior studies have examined the relationship of distracted driving and crash risk using national data, few if any studies have explored cross-national differences in mobile phone use on motor vehicle crash rates. We use longitudinal data for 23 countries to examine the association between rates of mobile phone subscribership and injuries and fatalities on public roadways. Methods Road safety data are reported by the Organization for Economic Co-operation and Development (OECD). We examine 23 OECD countries for the 11-year period, 2001–2011. Generalized least squares (GLS) regression is used to examine logged nonfatal injuries and fatalities per 100,000 population with the log number of mobile phone subscribers per 100 people, adjusting for number of motor vehicles (cars, buses, other), percent urban population, unemployment rate, GDP per capita, year and country fixed effects. Results From 2001 to 2011, countries experienced a 23.3% decline in rates of motor vehicle injuries—decreasing from 394.2 to 302.5 per 100,000 population. However, trends in motor vehicle crash injuries varied across countries. For example, Denmark and France experienced a more than 50% decrease in injury rates since 2001, but rates in Australia increased 4.4%, from 151.6 to 158.3 per 100,000 population. Mobile phone subscribership increased substantially in this period, but rates and growth also varied significantly across countries. For example, in Switzerland, an average of 10 persons per 100 have a mobile phone; this compares to 77.2 in Great Britain. Growth rates in subscribership ranged from 22.3% in Iceland to nearly 200% in Estonia and Turkey in the study period. GLS regression analysis suggests a significant and positive association between rates of mobile phone subscribership and motor vehicle crash injuries. A 10% increase in subscribers per 100 people is predicted to result in an increase of 12.0% (p Conclusions We present evidence that increasing rates of mobile phone subscribership may be associated with motor vehicle crash injuries. Distracted driving is a problem worldwide and, thus, more cross-national efforts are needed to identify best practices in policy implementation to help address this problem.
Retrograde trafficking of both Golgi complex and TGN markers to the ER induced by nordihydroguaiaretic acid and cyclofenil diphenol

Previous studies have shown that the Golgi stack and the trans-Golgi network (TGN) may play a role in capturing escaped resident endoplasmic reticulum (ER) proteins, and directing their retrograde transport back to that organelle. Whether this retrograde movement represents a highly specific or more generalized membrane trafficking pathway is unclear. To better understand both the retrograde and anterograde trafficking pathways of the secretory apparatus, we examined more closely the in vivo effects of two structurally unrelated compounds, the potent lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), and the non-steroidal estrogen cyclofenil diphenol (CFD), both of which are known to inhibit secretion. In the presence of these compounds, transport of vesicular stomatitis virus G membrane glycoprotein from the ER to the Golgi complex, and from the TGN to the cell surface, was inhibited potently and rapidly. Surprisingly, we found that NDGA and CFD stimulated the rapid, but not concomitant, retrograde movement of both Golgi stack and TGN membrane proteins back to the ER until both organelles were morphologically absent from cells. Both NDGA- and CFD-stimulated TGN and Golgi retrograde membrane trafficking were inhibited by microtubule depolymerizing agents and energy poisons. Removal of NDGA and CFD resulted in the complete, but not concomitant, reformation of both Golgi stacks and their closely associated TGN compartments. These studies suggest that NDGA and CFD unmask a generalized bulk recycling pathway to the ER for both Golgi and TGN membranes and, further, that NDGA and CFD are useful for investigating the molecular mechanisms that control the formation and maintenance of both the Golgi stack proper and the TGN.
Isotope Stratigraphy and Paleodepth Changes of Pennsylvanian Cyclical Sedimentary Deposits

Oxygen isotopes can record water depth changes because of the relationship between depth and temperature, and ice volume changes by its relation to the isotopic composition of sea water. Because of this, oxygen isotopes provide an excellent means of studying the conditions responsible for the formation of cyclical sedimentary deposits in the late Paleozoic. We have determined the isotope stratigraphy of two late Pennsylvanian units in north Texas, the Necessity Shale and the Colony Creek Shale, after having carried out detailed stdies of the depositional environments andfossil biotas in these units. Isotope data were obtained from fibrous calcite in the shells of the brachiopod Crurithyris planoconvexa, which is present throughout both shales. Preservation of original isotopic composition in fibrous calcite is indicated by preservation of original shell microstructure, absence of cathodoluminescence, low iron and manganese concentrations, and high sulfur concentration within shells. These characters were determined by plain light and cathodoluminescence microscoPy, microprobe, and SEM-EDS. In contrast, prismatic calcite from the outer shell layer and some outer margins of the fibrous shell layer are diagenetically altered. This alteration is recognized by visible cathodoluminescence, high iron and manganese concentrations, and low sulfur concentration. The two cycles studed can be divided into as many as four depth zones based on sedimentology, fossil biota, and position within transgressive and regressive sequence. From shallowest to deepest, they are the myalinid zone, fusulinid zone, ammonoid zone, and gondolellid zone. The deepest faunal zone, defined by the occurrence of the conodont Gondolelia, correlates with the maximum 8180 in the fibrous calcite of C. planoconvexa. This indicates that the 8180 of the brachiopods is recording a decrease in emperature associated with deepening of water, and that temperature effects are the major component of the oxygen isotopic signal present in the cycles. Using modern tropical ocean temperature profiles as an analogue for interpretation of the 180 stratigraphy, the depth change estimated for deposition of the Necessity cycle in the Brownwood area of Texas is at least 70 m. INTRODUCTION
Height Distribution Between Cloud and Aerosol Layers from the GLAS Spaceborne Lidar in the Indian Ocean Region

The Geoscience Laser Altimeter System (GLAS), a nadir pointing lidar on the Ice Cloud and land Elevation Satellite (ICESat) launched in 2003, now provides important new global measurements of the relationship between the height distribution of cloud and aerosol layers. GLAS data have the capability to detect, locate, and distinguish between cloud and aerosol layers in the atmosphere up to 40 km altitude. The data product algorithm tests the product of the maximum attenuated backscatter coefficient b'(r) and the vertical gradient of b'(r) within a layer against a predetermined threshold. An initial case result for the critical Indian Ocean region is presented. From the results the relative height distribution between collocated aerosol and cloud shows extensive regions where cloud formation is well within dense aerosol scattering layers at the surface. Citation: Hart, W. D., J. D. Spinhime, S. P. Palm, and D. L. Hlavka (2005), Height distribution between cloud and aerosol layers from the GLAS spaceborne lidar in the Indian Ocean region,
Laser Cooling Micromechanical Structures with High-Finesse Optical Cavities

We have realized a high-finesse optical cavity which incorporates a micromechanical cantilever. This cantilever’s response to radiation pressure can lead to optical nonlinearity, laser cooling, squeezing, and other quantum optical effects.
Evaluation of stature estimation from the database for forensic anthropology.

Abstract: Trotter and Gleser’s (1–3) stature equations, conventionally used to estimate stature, are not appropriate to use in the modern forensic context. In this study, stature is assessed with a modern (birth years after 1944) American sample (N = 242) derived from the National Institute of Justice Database for Forensic Anthropology in the United States and the Forensic Anthropology Databank. New stature formulae have been calculated using forensic stature (FSTAT) and a combined dataset of forensic, cadaver, and measured statures referred to as Any Stature (ASTAT). The new FSTAT-based equations had an improved accuracy in Blacks with little improvement over Ousley’s (4) equations for Whites. ASTAT-based equations performed equal to those of FSTAT equations and may be more appropriate, because they reflect both the variation in reported statures and in cadaver statures. It is essential to use not only equations based on forensic statures, but also equations based on modern samples.
Life-Threatening Hyperkalemia from Cream of Tartar Ingestion

Introduction Cream of tartar (potassium bitartrate) has a long history as a cooking aid and medicinal purgative. Despite containing large amounts of potassium, there are no well-documented cases of it causing toxicity. We report two cases in which intentional ingestions of cream of tartar resulted in life-threatening hyperkalemia. In addition, we briefly review the use of cream of tartar as a historical purgative.
What is the role of conservative primary surgical management of epithelial ovarian cancer: the United States experience and debate

Certification in Gynecologic Oncology and creation of the Society of Gynecologic Oncologists in the United States have led to the development of a specialty with individuals capable of performing complex abdominal and pelvic operations in the management of epithelial ovarian carcinoma. These operations can be divided into two types. 1) A staging operation to assess the extent of disease through careful palpation, histologic and cytologic assessment of all peritoneal surfaces along with removal of the uterus, ovaries and fallopian tubes, omentum, together with a bilateral pelvic and aortic lymphadenectomy. Such information allows the clinician to determine prognosis and if postoperative adjuvant therapy is indicated. 2) A debulking operation designed to resect or reduce the size of metastatic lesions as well as to remove the primary tumor including a bilateral salpingo-oophorectomy. This operation is designed to improve survival and cure. In spite of this apparently clear paradigm, there has been a steady debate as to the apparent justification of these operations, especially when the former is performed in a women who has not completed her childbearing and especially when the latter requires "ultraradical" procedures. Many feel that the pendulum is now swinging toward fertility-sparing surgery among young women with early invasive cancers and toward either neoadjuvant chemotherapy or less than ultraradical debulking among women with advanced ovarian cancer. The purpose of this study is not to provide an exhaustive review but rather to outline this debate and focus on the American experience with conservative surgery in the management of epithelial ovarian carcinoma.
Helix Folding of an Alanine-Based Peptide in Explicit Water

Computer simulations using full atomic representations for both the peptide and water molecules were performed to study the folding of a 16-residue alanine-based helical peptide in aqueous solution. Using a recently developed self-guided molecular dynamics (SGMD) method, which was shown to improve the conformational searching efficiency significantly as compared to conventional MD simulation method, reversible folding (folding, unfolding and refolding) of a 16-residue alanine-based synthetic peptide in explicit water at 274 K was successfully accomplished. Consistent with experimental results, the helix was found to be the major secondary structural element in aqueous solution, and among different helix forms, the α-helix is the dominant form. Conformational analysis of our simulation results showed that turns and 310-helices play an essential role in the folding of α-helix. Interestingly, our results showed that the propagation of a helix segment is more frequent at the C-end than at the N-end. In most h...
The Tyrosine Phosphorylation of Munc18c Induces a Switch in Binding Specificity from Syntaxin 4 to Doc2β

Glucose-stimulated insulin secretion is mediated by syntaxin 4-based SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes and the Sec1/Munc18 protein Munc18c. Our laboratory recently reported that Munc18c-syntaxin 4 complexes are further regulated by the competitive binding of the double C2 domain protein Doc2β to Munc18c, although the underlying mechanism for this is unknown. Because the Doc2β binding region of Munc18c contained residue Tyr-219 and this residue becomes phosphorylated in response to glucose stimulation, we hypothesized that the mechanism would involve Munc18c phosphorylation. Coimmunoprecipitation analyses using detergent lysates prepared from pervanadate-treated MIN6 beta cells revealed that the tyrosine phosphorylation of Munc18c corresponded to a 60% decrease in Munc18c-syntaxin 4 association with a coordinate 2-fold increase in Munc18c-Doc2β binding. In vitro binding assays identified syntaxin 4 residues 118-194 as sufficient to confer its interaction with Munc18c; residues 118-194 contain the Hc α-helix and flexible linker region controlling transition of syntaxins between closed and open conformations. When overexpressed in MIN6 cells, this Hc-linker region functioned as a competitive inhibitor of endogenous syntaxin 4-Munc18c binding, increased syntaxin 4 binding to VAMP2, and significantly enhanced glucose-stimulated secretion. Molecular modeling of these new interactions yielded the predictions 1) that Tyr-219 of Munc18c remains buried under basal conditions in a conformation that is favorable for interaction with “closed” syntaxin 4 and 2) that stimulation leads to changes in syntaxin 4 contacts to facilitate exposure of Munc18c Tyr-219 for phosphorylation and Doc2β binding.
Orphanin FQ/nociceptin blocks cocaine-induced behavioral sensitization in rats

Abstract Rationale. Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1–17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization. Objective. The present study was designed to examine the ability of OFQ/N to block cocaine-induced behavioral sensitization. Methods. Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ/N (15 nmol) followed by saline or cocaine (20 mg/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg/kg) in the absence of OFQ/N on day 8. The specificity of OFQ/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1–3. Finally, the effect of intra-VTA OFQ/N administration on cocaine sensitization was examined. Results. Sensitization did not develop in rats repeatedly treated with OFQ/N, via either route of administration, prior to cocaine administration on days 1–3. The inhibitory effect of OFQ/N was not dependent on context and was blocked by pretreatment with J-113397. Conclusion. Our results indicate that OFQ/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ/N.
Social support, attachment, and drug misuse in suicidal African American women

AbstractThis study examined social support and attachment in women with and without drug misuse. Data were collected from 146 African American female suicide attempters who presented at an inner-city hospital. MANOVAs revealed that compared to their counterparts who did not misuse drugs, women who reported drug misuse had lower levels of family and friend support (Social Support Behaviours Scale), lower scores on secure attachment and higher scores on fearful and dismissive attachments (Relationship Style Questionnaire). Low-social support and less secure attachments make treatment engagement challenging and require interventions designed to enhance participation.
Carbocyclic Carbene Ligands Derived from Aromatic Nitrones: Formation and Catalytic Activity of Their Pd(II) Complexes

Nitrones derived from aromatic aldehydes were shown to be convenient precursors to a novel class of carbocyclic carbene ligands. Air- and moisture-stable palladium complexes derived from the carboc...
Effects of daily cocaine and morphine treatment on somatodendritic and terminal field dopamine release.

: Daily injections of cocaine or morphine into rodents produces behavioral sensitization such that the last daily injection results in a greater motor stimulant effect than the first injection. To evaluate a role for brain dopamine in behavioral sensitization to cocaine and morphine, tissue slices from the ventromedial mesencephalon (containing dopamine cell bodies), the nucleus accumbens, and striatum (dopamine terminal fields) were obtained from rats pretreated with daily cocaine, morphine, or saline 2–3 weeks earlier. When the tissue slices were depolarized by increasing potassium concentration in the superfusate, the release of endogenous dopamine from the ventromedial mesencephalon of cocaine- and morphine-pretreated rats was significantly decreased. In contrast, the release of dopamine from the nucleus accumbens and striatum was either unaltered or slightly enhanced in rats pretreated with cocaine and morphine. When dopamine was released by amphetamine, a significant decrease in dopamine release from the ventromedial mesencephalon of cocaine-pretreated rats was measured. No other significant changes were measured after amphetamine-induced release. It is postulated that the decrease in dopamine release from the ventromedial mesencephalon of cocaine- and morphinesensitized rats results in less somatodendritic autoreceptor stimulation, and thereby produces an increase in dopamine neuronal activity.
PUROMYCIN INHIBITION OF AMYLASE SYNTHESIS IN THE PERFUSED RAT LIVER.

The production of amylase by the perfused, isolated rat liver is inhibited by puromycin. Whereas the average amylase production by normal livers is 38.7 units per gram of liver in 4 hours, with 5 mg. of puromycin added the amylase production dropped to 8.7 units per gram. When 10 mg. or more of puromycin were added, there was a net loss in amylase of the total system, i.e., plasma and liver combined. Addition of penicillin or oxytetracycline did not cause significant decrease in amylase production, indicating that the inhibiting effect of puromycin was not caused by its bactericidal properties. Puromycin aminonucleoside did not inhibit amylase production. Puromycin added in vitro to plasma or liver extracts had no effect on their amylase activities. The ability of puromycin, a specific inhibitor of protein synthesis, to block the amylase production of the liver without affecting blood flow or bile production strengthens our previous conclusion that the normal amylase increase in the system represents a true synthesis and is not an artifact.