cssi/SciSciGPT-SciSciNet huggingface dataset:
Segmentation of microcystic macular edema in Cirrus OCT scans with an exploratory longitudinal study

Microcystic macular edema (MME) is a term used to describe pseudocystic spaces in the inner nuclear layer (INL) of the human retina. It has been noted in multiple sclerosis (MS) as well as a variety of other diseases. The processes that lead to MME formation and their change over time have yet to be explained sufficiently. The low rate at which MME occurs within such diverse patient groups makes the identification and consistent quantification of this pathology important for developing patient-specific prognoses. MME is observed in optical coherence tomography (OCT) scans of the retina as changes in light reflectivity in a pattern suggestive of fluid accumulations called pseudocysts. Pseudocysts can be readily identified in higher signal-to-noise ratio (SNR) images, however pseudocysts can be indistinguishable from noise in lower SNR scans. In this work, we expand upon our earlier MME identification methods on Spectralis OCT scans to handle lower quality Cirrus OCT scans. Our approach uses a random forest classifier, trained on manual segmentation of ten subjects, to automatically detect MME. The algorithm has a true positive rate for MME identification of 0.95 and a Dice score of 0.79. We include a preliminary longitudinal study of three patients over four to five years to explore the longitudinal changes of MME. The patients with relapsing-remitting MS and neuromyelitis optica appear to have dynamic pseudocyst volumes, while the MME volume appears stable in the one patient with primary progressive MS.
Human Cysteine-Rich Intestinal Protein: cDNA Cloning and Expression of Recombinant Protein and Identification in Human Peripheral Blood Mononuclear Cells

Cysteine-rich intestinal protein (CRIP) is a small, 8.5-kDa protein with one double zinc-finger motif called a LIM domain. It is very abundant in intestine and some immune cells in rodents, and expression is influenced by development and the immune response. We have cloned a human CRIP cDNA from human small intestine poly(A)+ RNA by RT-PCR. Through sequencing, we found that the human intestinal CRIP protein (hCRIP) differed from the previously cloned rat CRIP by two amino acids (residues 8 and 58). hCRIP was expressed with the pET vector/bacterial system and isolated by gel filtration and ion-exchange chromatography. The protein was purified to homogeneity as confirmed by PAGE, Western blotting, and immunodetection. Recombinant hCRIP has a molecular mass of 8390 Da based on mass spectrum analysis. Southern analysis suggests that there are three copies of the CRIP gene in the human genome. hCRIP mRNA was detected by RT-PCR in human monocytes purified from peripheral blood and THP-1 cells, a human monocytic cell line. Incubation of THP-1 cells with 65Zn and chromatography of the cytosol show that a significant amount of the radioactivity is associated with CRIP as was shown previously for rat intestine. The results are consistent with a functional role for CRIP in proliferation/differentiation of specific cell types, particularly those associated with host defense.
Silencing the Call to Action: A Bird’s Eye View of Minority Language Media and Political Participation in Eurasia

Do citizens living in linguistically diverse countries without benefit of diverse media outlets find this to be a barrier to civic engagement? This study considers the interrelated effects of media access and social capital on political engagement in 15 Eurasian countries as that region continues to transition to an open economy and democracy. Drawing upon individual-level survey data, and controlling for relevant political and socioeconomic factors, regression analyses suggest a significant impact of media plurality, interpersonal trust, and government confidence on both voting turnout and unconventional political participation. The effect of social capital is mixed. Results indicate that higher levels of trust contribute to participation, while greater confidence in government is associated with less participation. These preliminary tests also show that collective action is generally lower in countries having greater linguistic diversity, but suggest that having access to political news in one’s own language can indeed contribute to more activism.
Forward, relaxed, and reverse selection for reduced and enhanced sensitivity to ethanol's locomotor stimulant effects in mice.

Background: Rarely have trait markers for alcoholism risk been identified. However, relative sensitivity to the arousing effects of ethanol and sensitivity to ethanol's sedative effects have been distinguished as potentially valuable behavioral risk factors. Both traits are genetically influenced and have been modeled in mice by measuring sensitivity to ethanol-induced locomotor stimulation and hypnosis. Reverse selection was performed to examine the hypothesis that forward selection for differential sensitivity to ethanol's locomotor stimulant effects resulted in homozygous fixation of selection trait-relevant alleles and to test the hypothesis that common genes influence ethanol's stimulant and sedative effects. Methods: Bidirectional selective breeding was completed for enhanced (FAST mice) and reduced (SLOW mice) sensitivity to ethanol's locomotor stimulant effects. Selection was terminated (relaxed), and the lines were tested to detect genetic drift. Reverse selection for enhanced sensitivity to ethanol-induced stimulation in SLOW mice and reduced sensitivity in FAST mice was performed for 16 generations. Forward and reverse selected lines were tested for sensitivity to ethanol's sedative effects by measuring duration of ethanol-induced loss of righting reflex. Results: Differential sensitivity to the sedative effects of ethanol emerged with selection for differential ethanol stimulation, indicating a common genetic influence on these traits. SLOW mice developed greater sensitivity to ethanol's sedative effects relative to FAST mice. Reverse selection, never before reported for a pharmacogenetic trait, was effective in eliminating most of the difference in stimulant sensitivity between the FAST and SLOW lines and also eliminated the difference in loss of righting reflex duration. Conclusions: Residual heterozygosity persisted at trait-relevant loci even at the selection plateau, possibly due to heterosis, natural selection favoring heterozygosity, or epistatic phenomena involving differences in the sets of genes regulating the high- versus low-sensitivity traits. They also suggest that some common genes influence sensitivity to ethanol's locomotor stimulant and sedative effects.
Conformational Changes in Bacteriophage P22 Scaffolding Protein Induced by Interaction with Coat Protein

Abstract Many prokaryotic and eukaryotic double-stranded DNA viruses use a scaffolding protein to assemble their capsid. Assembly of the double-stranded DNA bacteriophage P22 procapsids requires the interaction of 415 molecules of coat protein and 60–300 molecules of scaffolding protein. Although the 303-amino-acid scaffolding protein is essential for proper assembly of procapsids, little is known about its structure beyond an NMR structure of the extreme C-terminus, which is known to interact with coat protein. Deletion mutagenesis indicates that other regions of scaffolding protein are involved in interactions with coat protein and other capsid proteins. Single-cysteine and double-cysteine variants of scaffolding protein were generated for use in fluorescence resonance energy transfer and cross-linking experiments designed to probe the conformation of scaffolding protein in solution and within procapsids. We showed that the N-terminus and the C-terminus are proximate in solution, and that the middle of the protein is near the N-terminus but not accessible to the C-terminus. In procapsids, the N-terminus was no longer accessible to the C-terminus, indicating that there is a conformational change in scaffolding protein upon assembly. In addition, our data are consistent with a model where scaffolding protein dimers are positioned parallel with one another with the associated C-termini.
The Linguistic Minority Parents' Perceptions of Bilingual Education.

Abstract The purpose of this study was twofold: (a) to examine the linguistic minority parents’ perceptions of bilingual education and (b) to investigate their views on bilingual education. This study was motivated by the re-emerging controversy surrounding the issue of whether or not public schools should continue to provide bilingual education programs for linguistic minority students. It was hypothesized that most parents of linguistic minority students did not fully understand the objectives and goals of bilingual education. It was also hypothesized that irrespective of their understanding level, most linguistic minority parents supported bilingual education as long as it provided their children the opportunities to develop English skills while providing them equal access to the core curriculum. Based on a sample of 290 adult subjects, all of whom were of Latino background, the study found that the majority did not know the different models or programs of bilingual education. Nevertheless, three out o...
Medical pluralism on a Guatemalan plantation.

Abstract This paper examines the alternative medical resources and treatments utilized by a population on a Guatemalan coffee and sugar plantation. This is part of a larger multidisciplinary project concerning the assessment of the health and nutritional status of this population. The study revealed a pluralistic complex of multiple and simultaneous usage including home remedies, curanderos, herbalists, midwives, spiritists, shamans, injectionists, pharmacists, private physicians, public and private clinics, and hospitals. These resources include and combine aspects from Mayan Indian, folk Ladino, spiritism and cosmopolitan medical traditions. The pluralistic dimensions of health care are analyzed in terms of the heterogeneous medical behavior of both the health seeker and the practitioners or specialists, emphasizing how components from the various traditions are incorporated or utilized. Case studies are used to illustrate some of the health care strategies used by the population.
The effects of tartar-control toothpaste on the oral soft tissues

Ninety-two dental and dental hygiene students completed a double-blind, controlled clinical trial. The purpose of the trial was to evaluate the effects of toothpastes, in varying concentrations of flavor and tartar-control agents. Four formulations of toothpastes were assessed: (A) control-low flavor with no tartar control; (B) medium flavoring with medium tartar control; (C) high flavoring with medium tartar control; and (D) medium flavoring with no tartar control. Soft tissue reactions were assessed objectively and independently by three examiners. Subjective perceptions about each toothpaste were gathered by a structured, open-ended questionnaire. The "tartar control" toothpastes, B and C, resulted in statistically significant (p less than 0.005) higher rates of mucosal reactions (e.g., ulceration, sloughing, erythema, migratory glossitis) than the "non-tartar control" toothpastes A and D. When the oral mucosal reaction rates were adjusted for multiple clinical observations within each subject at the same point in time there was no statistically significant (p greater than 0.05) difference between male (0.25) and female (0.28) subjects. In this study population, the order of preference was observed as toothpaste A greater than D greater than B greater than C. The major reasons for disfavor were burning sensation in toothpastes C (2.4%) and B (4%).
Dynamic one-dimensional modeling of secondary settling tanks and design impacts of sizing decisions

Abstract As one of the most significant components in the activated sludge process (ASP), secondary settling tanks (SSTs) can be investigated with mathematical models to optimize design and operation. This paper takes a new look at the one-dimensional (1-D) SST model by analyzing and considering the impacts of numerical problems, especially the process robustness. An improved SST model with Yee–Roe–Davis technique as the PDE solver is proposed and compared with the widely used Takacs model to show its improvement in numerical solution quality. The improved and Takacs models are coupled with a bioreactor model to reevaluate ASP design basis and several popular control strategies for economic plausibility, contaminant removal efficiency and system robustness. The time-to-failure due to rising sludge blanket during overloading, as a key robustness indicator, is analyzed to demonstrate the differences caused by numerical issues in SST models. The calculated results indicate that the Takacs model significantly underestimates time to failure, thus leading to a conservative design.
Introduction to the Special Issue on Analytics in Sports, Part II: Sports Scheduling Applications

Part II of this Special Issue on Analytics in Sports is devoted to sports scheduling applications. Sports scheduling has proven to be an exceptionally successful application area for operations research. The papers in this issue demonstrate the breadth of applications for sports scheduling. The sports addressed include baseball, volleyball, Canadian football, softball, and soccer. The sports leagues where scheduling methods are applied range from youth recreation leagues to multibillion-dollar professional leagues. In addition, the articles originate from five countries illustrating the international scope of sports scheduling applications.
Evaluation of cold-water carbonates as a possible paleoclimatic indicator

Abstract The common belief currently shared by many geoscientists concerning the climatic interpretation of limestones is that a warm-water environment is essential. This concept is not necessarily true because the rate and extent of terrigenous sediment dilution, rather than water temperature, is the primary factor determining whether or not a limestone forms at nearshore or continental shelf depths. Because carbonate productivity is lowest in cold climates, however, CaCO3 abundance and the thickness of carbonate accumulations tend to be least at high latitudes. In this regard present-day continental shelves and beaches offer a poor model for comparing cold-water and warm-water carbonates because of the generally emergent continental tectonic framework, recent eustatic sea-level changes, and the presence of ice caps at the modern poles. Typically, the influence of climate on non-reef continental shelf and beach environments cannot be clearly distinguished by the presence or absence of major taxonomic groups. Faunal diversity and equitability are more sensitive in this regard. The absence of shelf-depth inorganic carbonate precipitates, micrite envelopes, and peloids may also point to the cold-water origin of a rock. Skeletal mineralogy and oxygen isotopes of certain unrecrystallized carbonates may be good paleoclimatic indicators; however, trace elements and physical-textural attributes of the carbonate fraction are probably temperature insensitive. Previous studies of high-latitude continental shelves have concentrated merely on the abundance of calcareous material and there is seemingly a disproportionate amount of information with respect to low-latitude carbonate studies. Further research on cold-water carbonates may open up new avenues for alternative paleoenvironmental and paleoclimatic interpretations.
A Defect in the p53 Response Pathway Induced by de Novo Purine Synthesis Inhibition

p53 is believed to sense cellular ribonucleotide depletion in the absence of DNA strand breaks and to respond by imposition of a p21-dependent G1 cell cycle arrest. We now report that the p53-dependent G1 checkpoint is blocked in human carcinoma cell lines after inhibition of de novo purine synthesis by folate analogs inhibitory to glycinamide ribonucleotide formyltransferase (GART). p53 accumulated in HCT116, MCF7, or A549 carcinoma cells upon GART inhibition, but, surprisingly, transcription of several p53 targets, including p21cip1/waf1, was impaired. The mechanism of this defect was examined. The p53 accumulating in these cells was nuclear but was not phosphorylated at serines 6, 15, and 20, nor was it acetylated at lysines 373 or 382. The DDATHF-stabilized p53 bound to the p21 promoter in vitro and in vivo but did not activate histone acetylation over the p53 binding sites in the p21 promoter that is an integral part of the transcriptional response mediated by the DNA damage pathway. We concluded that the robust initial response of the p53 pathway to GART inhibitors is not transcriptionally propagated to target genes due to a defect in p53 post-translational modifications and a failure to open chromatin structure despite promoter binding of this unmodified p53.
Fast broadband inversion by adiabatic pulses

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes.
On the coupling between the double layer and the solvent polarization fields

Abstract An approach is developed to incorporate in the standard theory of the double layer the effect of the solvent polarization. This polarization is due to a source of polarization on the surface and to the charges in the diffuse layer. The new equations lead to the conclusion that a diffuse layer can be generated even in the absence of a surface charge as long as there is some source of polarization on the surface, such as a layer of dipoles. The solvent polarization also changes the surface potential.
Nanometer scale precipitation in ferritic MA/ODS alloy MA957

The microstructure of a commercial mechanically-alloyed oxide dispersion strengthened MA957 alloy has been characterized in the as-received condition and after annealing for up to 24 h at 1300 °C (∼0.85 Tm) by atom probe tomography and electron microscopy. Atom probe tomography revealed a high number density of ultrafine 2-nm-diameter Ti-, Y- and O-enriched particles in the ferrite matrix in the as-received condition. The size increased and the number density of these particles decreased during the annealing treatment for 1 and 24 h at 1300 °C. Some coarser (∼10 nm) Ti-, Y- and O-enriched precipitates were also observed at the grain boundaries. No significant grain growth or recrystallization was observed during the high temperature annealing treatment.
Narcissism and embellishments of signature.

30 male and 20 female college students completed a measure of narcissism and signed a simulated birthday card with the instructions to embellish their signatures as they normally would if sending the card to a good friend. While narcissism scores did not differ significantly between sexes, women who did choose to embellish their signatures with multiple exclamation points and underlinings had significantly higher narcissism scores than women who did not. Men added significantly fewer embellishments to their signatures than women, and their embellishments did not appear to be related to their narcissism scores.
Neural networks for classified vector quantization of images

Recently, vector quantization (VQ) has received considerable attention and become an effective tool for image compression. It provides high compression ratios and simple decoding processes. However, studies on practical implementation of VQ have revealed some major difficulties such as edge integrity and codebook design efficiency. Over the past few years, a new wave of research in neural networks has emerged. Neural networks models have provided an effective alternative to solving computationally intensive problems. In this paper, we propose to implement VQ for image compression based on neural networks. Separate codebooks for edge and background blocks are designed using Kohonen self-organizing feature maps to preserve edge integrity and improve the efficiency of codebook design. Improved image quality has bee achieved and the comparability of new attempts with existing VQ approaches has been demonstrated with experimental results.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Genetic dissection of bacterial speck disease resistance in tomato

The bacterial speck disease of tomato has been developed as a model system to elucidate the molecular basis of specificity in plant-bacterial interactions and to study signal transduction events involved in the expression of plant disease resistance. We have employed a mutagenic approach to define the steps involved in the expression of disease resistance to the bacterial pathogen, Pseudomonas syringae pv. tomato (Pst) Eleven disease susceptible mutants have been identified and characterized twith altered recognition of Pst strains that express the avirulence gene avrPto. Genetic analysis of these mutants has revealed that they fall into two complementation groups. Five of the mutants map at the Pto locus, while six map a new locus that we have termed Prf. Further characterization of these mutants has revealed that the mutants that map at Pto are still sensitive to the insecticide fenthion, while the prf mutants are altered in resistance and also are insensitive to fenthion. Genetic mapping has also determined that the Prf locus maps near Pto. We are currently employing a map-based cloning strategy to isolate the Prf locus.
Time-dependent Navier-Stokes computations of separated flows over airfoils

The application of both a central-difference and an upwind implicit approximate factorization Navier-Stokes algorithm to highly separated flow is described. Using the thin-layer approximation, both algorithms are employed to solve the low Reynolds number laminar flow around a circular cylinder with periodic shedding. Results agree with experimental Strouhal numbers to within about 10 percent. A grid refinement study is conducted using the upwind code for both the thin-layer and complete Navier-Stokes approximations. The circular cylinder solution is shown to be highly dependent upon both grid density outward from the body and grid extent. Finally, the thin-layer central-difference code is used to predict the time-accurate unsteady flow about two stalled airfoils. The NACA 0012 airfoil turbulent solutions are periodic with Strouhal numbers of about 0.1; a strong vortex is periodically shed from the leading edge. The LS(1)-0417 airfoil turbulent solution shows a high frequency oscillatory trailing edge separation. The 20 degree NACA 0012 airfoil solution is massively separated, but shows no evidence of periodicity.
Improved techniques for heavy-ion simulation of neutron radiation damage

Abstract The ORNL facility for heavy-ion simulation of neutron damage is described. Two accelerators are operated simultaneously to propel two or three ion beams on the target under well-controlled conditions. The beams are generated continuously or in a pulsed mode. The heavy-ion beam is focused and analyzed in a unique way while the simultaneous light-ion beam is energy-ramped periodically to produce a more favorable implantation profile. Measurements of such profiles as well as beam compositions are presented and their significance discussed. The target normally consists of nine electron microscopy specimens whose temperature can be adjusted from 400–850 °C and accurately measured and controlled. The ultrahigh vacuum target chamber accomodates up to 54 TEM specimens at a single loading. The vacuum environment can be characterized by a partial pressure analysis. An example of the use of the facility for studying radiation damage of stainless steel is presented.
Inhibition of the growth of caki-I human renal adenocarcinoma in Vivo by luteinizing hormone-releasing hormone antagonist cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II

BACKGROUND Metastatic or recurrent renal cell carcinoma (RCC) is a therapeutic challenge because it is resistant to chemotherapy and external radiotherapy. No uniformly effective therapeutic agents are available for the management of patients with RCC. Hormones and growth factors may play a role in promoting the transformation and/or proliferation of kidney neoplasms. METHODS Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75), somatostatin analog RC-160, and bombesin antagonist RC-3940-II were tested for their effects on the growth of the Caki-I renal adenocarcinoma cell line xenografted into nude mice. RESULTS After 4 weeks of treatment, tumor volume was significantly (P < 0.01) decreased in animals receiving RC-160, to 167.5 ± 34.2 mm3, compared with the control group (485.7 ± 77.2 mm3). LH-RH antagonist SB-75 and bombesin antagonist RC-3940-II also significantly reduced the volume of Caki-I tumors, to 159.9 ± 18.1 and 234.7 ± 81.8 mm3, respectively. Somatostatin analog RC-160 decreased serum levels for growth hormone (GH) and insulin-like growth factor-I compared with controls. Treatment with RC-160, Cetrorelix, and RC-3940-II significantly reduced the number of high-affinity receptors for epidermal growth factor on Caki-I tumors. CONCLUSIONS LH-RH antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II effectively inhibit the growth of human Caki-I renal adenocarcinomas in nude mice. These peptide analogs should be considered for the therapy of patients with metastatic or recurrent RCC. Cancer 1998;82:909-17. © 1998 American Cancer Society.
Racial and Ethnic Change and Serious Student Offending in Los Angeles Middle and High Schools

This study assesses the relationship between racial and ethnic change and change in crime in a different type of community—schools. Like neighborhoods, some schools are perpetually more dangerous than others despite turnover. This study investigates how change in the racial and ethnic composition of school enrollment plays a role in school-level crime. In addition, because schools are located within a community context, this study incorporates spatial context and includes information on crime and residential change in the neighborhood surrounding the school. Using a series of negative binomial regression models assessing the influence of changes in school-specific and local community factors on serious school offending (assaults, batteries, robberies, and property offenses that occurred on campus) over time, the findings reveal that that the relationship between school-level racial and ethnic change is moderated by the community-level changes, but that the relationship is specific to school type and contr...
Accuracy of information on printed over-the-counter drug advertisements.

Abstract Direct-to-consumer drug advertising is a useful medium for educating people and disseminating product information. Consumers make product purchase decisions based on the information gained from advertisements. If advertisements are misleading, consumers may not have adequate drug knowledge to detect this misinformation. The objective of this study was to evaluate print advertisements for over-the-counter (OTC) products. Five clinical pharmacists evaluated print advertisements appearing in three consumer periodicals. Advertisements were selected over a nine month period beginning 1994. Accuracy of information on OTC advertisements was determined based on federal guidelines. Additionally, reviewers identified deficiencies in advertisements that may mislead consumers. According to reviewers, around 50% of advertisements lacked accurate statements. Side effects were indicated on only one advertisement. All advertisements were indicated by reviewers to be more promotional than educational. Reviewers i...
Detection and partial characterization of ocular cicatricial pemphigoid antigens on COLO and SCaBER tumor cell lines

Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune inflammatory disease which affects the conjunctiva and other squamous epithelial mucous membranes resulting in a scarring process. It is characterized by the deposition of an antibasement membrane zone (BMZ) antibody In vivo. Sera from 11 patients with active OCP were studied. Using monkey esophagus and normal skin as substrate. weak staining of the BMZ was observed in conventional indirect immunofluorescence (IIF) assay. Using salt split human skin as substrate, the OCP sera demonstrated binding to the epidermal side of the split, in low titers with weak staining. Ten of the 11 sera were positive on an immunoblot assay using COLO and SCaBER tumor cell lysates demonstrating 230, 205. 160, and 85 kD proteins. Sera from six bullous pemphigoid (BP) patients, with only cutaneous involvement and high titer of anti-BMZ antibody. as detected by IIF, also bound to 230. 160. and 85 kD proteins on both lysates in comigration experiments. Serum from five no...
Defense science board recommendations: an examination of defense policy on the use of modeling and simulation

The Defense Science Board Task Force on Improving Test and Evaluation Effectiveness was requested to look at ways of improving the use of modeling and simulation as tools in the test and acquisition of US Defense Department systems. The author discusses the conclusions and recommendations of the Task Force. It is pointed out that it is extremely important to avoid operational test surprises, for reasons of both cost and credibility. This can be done by performing more operational testing during development, enabling developers to learn about problem areas while they still can be fixed rather than waiting until the system is fielded. It also helps to develop evaluation frameworks at the onset to specify how evaluation is to be performed; as the real program progresses, these must be upgraded so that they are consistent with the state of knowledge. Operational tests must be involved so that there are no unanticipated gaps or changes in viewpoint. >
Drug-induced hypersensitivity syndrome in a premature infant

Fever, skin reactions, and limb edema because of drug-induced hypersensitivity have been reported in children because of various drugs, mainly aromatic antiepileptic drugs such as phenytoin, phenobarbital, carbamazepin, and primidone. The skin reactions differ in severity and range from mild maculopapular erythema to exfoliative dermatitis. They have been described in older children but have not been reported in newborn infants. We report a premature newborn infant who developed fever, skin reactions, and edema because of phenytoin while receiving anticonvulsant therapy.
Pyran Template Approach to the Design of Novel A3 Adenosine Receptor Antagonists.

[Table: see text] A3 adenosine receptor antagonists have potential as anti-inflammatory, anti-asthmatic, and anti-ischemic agents. We previously reported the preparation of chemical libraries of 1,4-dihydropyridine (DHP) and pyridine derivatives and identification of members having high affinity at A3 adenosine receptors. These derivatives were synthesized through standard three-component condensation/oxidation reactions, which permitted versatile ring substitution at five positions, i.e., the central ring served as a molecular scaffold for structurally diverse substituents. We extended this template approach from the DHP series to chemically stable pyran derivatives, in which the ring NH is replaced by O and which is similarly derived from a stepwise reaction of three components. Since the orientation of substituent groups may be conformationally similar to the 1,4-DHPs, a direct comparison between the structure activity relationships of key derivatives in binding to adenosine receptors was carried out. Affinity at human A3 receptors expressed in CHO cells was determined vs. binding of [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-N-methyl-carbamoyladenosine). There was no potency-enhancing effect, as was observed for DHPs, of 4-styryl, 4-phenylethynyl, or 6-phenyl substitutions. The most potent ligands in this group in binding to human A3 receptors were 6-methyl and 6-phenyl analogs, 3a (MRS 1704) and 4a (MRS 1705), respectively, of 3,5-diethyl 2-methyl-4-phenyl-4H-pyran-3,5-dicarboxylate, which had Ki values of 381 and 583 nM, respectively. These two derivatives were selective for human A3 receptors vs. rat brain A1 receptors by 57-fold and 24-fold, respectively. These derivatives were inactive in binding at rat brain A2A receptors, and at recombinant human A2B receptors displayed Ki values of 17.3 and 23.2 μM, respectively. The selectivity, but not affinity, of the pyran derivatives in binding to the A3 receptor subtype was generally enhanced vs. the corresponding DHP derivatives.
Process improvement: a classroom experiment

The authors describe a classroom experiment that demonstrates many topics which are related to process improvement. The students are assigned random numbers and asked to pass a ball, in number order, in the shortest time possible without dropping the ball. This pedagogical experiment illustrates a variety of concepts related to process improvement that are often difficult to teach without having a real life example. By actively taking part in the experiment, students gain a better understanding of process improvement concepts.
TORC2 and eisosomes are spatially interdependent, requiring optimal level of phosphatidylinositol 4, 5-bisphosphate for their integrity

The elucidation of the organization and maintenance of the plasma membrane has been sought due to its numerous roles in cellular function. In the budding yeast Saccharomyces cerevisiae, a novel paradigm has begun to emerge in the understanding of the distribution of plasma membrane microdomains and how they are regulated. We aimed to investigate the dynamic interdependence between the protein complexes eisosome and TORC2, representing microdomains MCC and MCT, respectively. In this study, we reveal that the eisosome organizer Pil1 colocalizes with the MCT marker Avo2. Furthermore, we provide evidence that the formation of MCT is dependent on both eisosome integrity and adequate levels of the plasma membrane phosphoinositide PI(4,5)P2. Taken together, our findings indicate that TORC2, eisosomes, and PI(4,5)P2 exist in an interconnected relationship, which supports the emerging model of the plasma membrane.
Mechanical Properties of Lead-Free Solders

Mechanical testing of solder joint arrays was used to characterize lead-free solder alloys under both shear and tensile loading. The alloys studied included Sn4.0Ag0.5Cu, Sn3.5Ag, Sn0.7Cu, Sn3.0Ag0.5Cu, and Sn1.2Ag0.5Cu0.05Ni. All of the lead-free alloys exhibited time and temperature dependent creep behavior over the entire temperature range from -55 C to 125 C. A SINH creep law was effective in describing the steady state creep behavior over the entire range of conditions. Lead-free alloy strength increases with increasing Ag content. The relative strength of tin-lead versus lead-free alloys depends on the strain rate and temperature regime. At high strain rates and low temperatures, eutectic tin-lead is the strongest alloy. At low strain rates and high temperatures, eutectic tin-lead is the lowest strength alloy. Simulated stress-strain hysteresis loops for both accelerated test and field use conditions showed dramatic differences between the various alloys. Higher Ag content results in a larger stress range but a smaller strain range during temperature cycling.
Pediatric Anesthesia for Cardiac Catheterization and Electrophysiology Studies

In recent years interventional procedures have been intro duced to the field of pediatric catheterization. These proce dures continue to develop and be applied to patients with reduced cardiovascular reserve as an alternative to cardiac surgery or when cardiac surgery with cardiopulmonary by pass is contraindicated. More frequently anesthesiologists are being called on to provide support in sedating, anesthe tizing, or resuscitating these patients. As more compli cated procedures are performed, the anesthetist plays a pivotal role in the management of the patient to prevent mortality and major morbidity in the cardiac catheterization laboratory.
Exostosis and seizures in an adolescent refugee patient-case study of pseudohypoparathyroidism

Pseudohypoparathyroidism is a complex endocrine disorder caused by various possible biochemical receptor abnormalities of the parathyroid hormone. Phenotypical features that result depend heavily on the type of pseudohypoparathyroidism and genetic inheritance (maternal versus paternal inheritance). We discuss a case of an 18-year-old female refugee who presented as a new patient with multiple complaints including seizure disorder fitting the phenotypical syndrome known as Albright's hereditary osteodystrophy. Allopathic treatment and theoretical osteopathic therapies that can be used are discussed.
How Best to Evaluate Clinician–educators and Teachers for Promotion?

ABSTRACT The challenge of how best to evaluate educational scholars (and specifically, clinician—educators) and teachers for promotion continues to confront academia. While the work of educational scholars and teachers often overlaps, the terms for justifying their promotion differ substantially. In each case, the author maintains that evaluation should be oriented to evidence of the impact of their work. Educational scholars can be assessed mainly by objective impact, whereas the evidence for the impact of teachers should include profound, subjective effects on individual learners. For example, for clinician—educators engaged in scholarly work, the impact of that work can be identified in terms of changes in educational methods, career commitments, and practices (all intermediate outcomes), and even health outcomes. For teachers, in addition to customary criteria such as critical thinking, depth of knowledge, communication ability, and personal engagement, learners can be asked about the deep influence of these teachers. The author states his case for these principles, and also presents an innovative tool, the “impact map,” as a way of graphically portraying the track record of an individual clinician—educator. Such maps are more vivid than narrative testimonials in organizing and displaying evidence of impact over time. This tool, combined with the author's other suggestions to assist the promotion process for educators and teachers, is aimed at fostering a greater emphasis on outcomes in assessing both clinician—educators and teachers to achieve greater rigor and fairness.
Radiative transfer in ocean turbulence and its effect on underwater light field

[1] Turbulence in the upper ocean generates fluctuations in temperature and salinity, which result in variations in inherent optical properties (IOPs) and further change the underwater light field. A simulation-based study is performed for the radiative transfer (RT) of natural light in the turbulent flows in the upper ocean. For a canonical problem of turbulent shear flow interacting with the sea surface with and without surface waves, large-eddy simulations are performed for fluid motions and the transport of temperature and salinity. Based on the resolved turbulence temperature and salinity fields, IOP variations are quantified, and the inhomogeneous RT equation is then simulated using a Monte Carlo method. Through the simulations of a variety of cases with different flow, temperature, and salinity conditions, the statistics of downwelling irradiance are quantified and analyzed. It is found that the vertical profile of the mean downwelling irradiance is mainly determined by the vertical structure of the mean values of the IOPs; and turbulence effect is manifested in the horizontal variations of the downwelling irradiance. The magnitude of the irradiance variation is governed by the differences in the temperature and salinity between their values at the surface and in the deep region. In the presence of surface waves, the irradiance variation is enhanced due to the surface deformation, which is also largely affected by wave–turbulence interaction. The LES and inhomogeneous RT simulation may provide a useful tool for the characterization of upper-ocean turbulence processes based on underwater RT measurements.
Kinematic structure of an Atlantic cloud cluster during GATE and its time variation

This study uses the G ATE ( G ARP A tlantic T ropical E xperiment) upper air network in the tropics combined with high resolution SMS-1 ( S ynchronous M eteorological S atellite) derived winds at low levels, to identify the time-varying kinematics, and mass flux within the region of an intense cloud cluster on September 5, 1974. Satellite data was stored, displayed, and processed on the M an- C omputer I nteractive D ata A ccess S ystem (McIDAS). Measurements of cloud area expansion covering 20 h determined the cloud cluster stages. Quantitative measurements of the mass flux and kinematic properties of the cluster are given for the growth, growth-mature, and mature-dissipating stages of the cluster. In the growth phase of the cluster strong convergence exists below 900 mb. Relative winds show that the mass inflow to the cluster comes from the west-southwest below 950 mb within the subcloud layer. During the growth-mature stage deep convective system dominates the cluster. Strong low level convergence decreases as divergence at 250 mb becomes dominant. In the growth stage downward motion exists above 600 mb, which becomes strongly upward as the cluster matures. Maximum vertical motion shifts from 800 to 300 mb in the mature-dissipating stage. A mass budget quantitatively describes the horizontal and vertical mass exchanges in and around the cluster. In the growth stage subcloud layer air is horizontally transported from distances greater than 300 km from the cluster center, transported upward in the cluster, and exits in the 800–600 mb layer. The growth-mature stage, characterized by wide-spread deep convection shows that mass is raised at the 200–250 mb layer, where it is transported northward. Most of this mass is supplied by the large scale flow of warm moist air below 950 mb. Relative winds show that deep convection in the cluster is responsible for the upward transport of equatorial air to higher latitudes, supporting the view that cloud clusters are an integral part of the Hadley circulation cell. DOI: 10.1111/j.2153-3490.1980.tb00971.x
Hydrogen leakage into simple geometric enclosures

Abstract The following is a simplification of the hydrogen risk assessment method (Advances in Hydrogen Energy, Kluwer Academic Publishers, Plenum Press, Dordrecht, New York. p. 163–173. Proceedings of an American Chemical Society Symposium On Hydrogen Production, Storage and Utilization, August 22–26, New Orleans, Louisiana, 1999; Chemical Health and Safety 6 (3) (1999) 28.) previously developed at the University of Miami. It has been determined that in simple geometric enclosures, hydrogen leaks can be simulated using helium to predict the concentrations of the gas found near the ceiling after the initial transients disappear.
Hypoxic regulation of the fetal cerebral circulation

Fetal cerebrovascular responses to acute hypoxia are fundamentally different from those observed in the adult cerebral circulation. The magnitude of hypoxic vasodilatation in the fetal brain increases with postnatal age although fetal cerebrovascular responses to acute hypoxia can be complicated by age-dependent depressions of blood pressure and ventilation. Acute hypoxia promotes adenosine release, which depresses fetal cerebral oxygen consumption through action of adenosine on neuronal A1 receptors and vasodilatation through activation of A2 receptors on cerebral arteries. The vascular effect of adenosine can account for approximately half the vasodilatation observed in response to hypoxia. Hypoxia-induced release of nitric oxide and opioids can account for much of the adenosine-independent cerebral vasodilatation observed in response to hypoxia in the fetus. Direct effects of hypoxia on cerebral arteries account for the remaining fraction, although the vascular endothelium contributes relatively little to hypoxic vasodilatation in the immature cerebral circulation. In contrast to acute hypoxia, fetal cerebral blood flow tends to normalize during acclimatization to chronic hypoxia even though cardiac output is depressed. However, uncompensated chronic hypoxia in the fetus can produce significant changes in brain structure and function, alteration of respiratory drive and fluid balance, and increased incidence of intracranial hemorrhage and periventricular leukomalacia. At the level of the fetal cerebral arteries, chronic hypoxia increases protein content and depresses norepinephrine release, contractility, and receptor densities associated with contraction but also attenuates endothelial vasodilator capacity and decreases the ability of ATP-sensitive and calcium-sensitive potassium channels to promote vasorelaxation. Overall, fetal cerebrovascular adaptations to chronic hypoxia appear prioritized to conserve energy while preserving basic contractility. Many gaps remain in our understanding of how the effects of acute and chronic hypoxia are mediated in fetal cerebral arteries, but studies of adult cerebral arteries have produced many powerful pharmacological and molecular tools that are simply awaiting application in studies of fetal cerebral artery responses to hypoxia.
Unearthing the Goddess Within: Feminist Revisionist Mythology in the Poetry of Margaret Atwood

“The voyage of discovery is not in seeking new landscapesbut in having new eyes.”—Marcel ProustWe are Eve, Mother Earth, the Madonna, Desdemona, Medusa, Persephone, all embodiments of male-created ...
Language understanding is grounded in experiential simulations: a response to Weiskopf

Abstract Several disciplines within the cognitive sciences have advanced the idea that people comprehend the actions of others, including the linguistic meanings they communicate, through embodied simulations where they imaginatively recreate the actions they observe or hear about. This claim has important consequences for theories of mind and meaning, such as that people’s use and interpretation of language emerges as a kind of bodily activity that is an essential part of ordinary cognition. Daniel Weiskopf presents several arguments against the idea that experiential simulations play a major role in immediate language use and meaning. We offer several rebuttals to Weiskopf, in which we critique his interpretation of simulation theory, present additional psycholinguistic evidence supportive of the simulation perspective, and suggest that a more traditional theory of linguistic meaning and processing has little psychological and empirical validity.