cssi/SciSciGPT-SciSciNet huggingface dataset:
An experimental investigation of the explosive effect in almost common value auctions

Abstract With only two bidders, a slight private value advantage in a common value auction is predicted to have an explosive effect on the allocation and revenue of the auction when using a second price and/or English clock mechanism. This paper uses the “wallet game” in an English clock mechanism with two players to test these predictions. The results show that the effect is proportional, not explosive, confirming the results of past experiments. A behavioral model with two types of players, naive and sophisticated, is developed and tested against the experimental data. In the model, naive players use a rule of thumb bidding function, while the sophisticated players are fully rational and, when forming their strategy (choosing the best response), correctly account for the probability that a rival is naive or sophisticated. We use cluster analysis to classify the players in the symmetric auctions as naive or sophisticated and a strict win/lose criteria to classify players in the asymmetric auctions. We find that those players classified as sophisticated are more aggressive in responding to high signals or advantaged status than their naive counterparts, but do not lower their bids relative to the naive players when receiving low signals or when regular.
Electrical Stimulation Induces the Level of TGF-β1 mRNA in Osteoblastic Cells by a Mechanism Involving Calcium/Calmodulin Pathway

Abstract It is well-known that electrical stimulation can prompt healing of bone fractures. However, the mechanism involved is less clear. In this study, we found that capacitively coupled electric field-induced proliferation of osteoblastic cells (MC3T3-E1) accompanied increased levels of transforming growth factor-beta 1 (TGF-β1) mRNA determined by quantitative reverse transcription/polymerase chain reaction. Previous reports have shown that verapamil and W-7, both of which block voltage gated calcium channels and inhibit the activation of cytosolic calmodulin, respectively, blocked capacitively coupled electric field-induced proliferation of the osteoblast cells. Interestingly, we found that verapamil and W-7 can also block capacitively coupled electric field-induced elevation of TGF-β1 mRNA. This result suggested that electrical stimulation induces the level of TGF-β1 mRNA in osteoblastic cells by a mechanism involving calcium/calmodulin pathway. The potential roles of TGF-β in the electrical signal-induced osteogenesis was discussed.
Emily and Rebecca: A Tale of Two Teachers.

Abstract Using a qualitative study, two teachers, Emily and Rebecca, who started their teaching careers in their forties were interviewed and followed for 3 years to document their experiences in the teaching profession. The tale of these two teachers includes their joys, frustrations, and problems that surround their lives as middle school math teachers. Discussing such topics as, college preparation, isolation, time required, extra duties, little respect for teachers, resistance to innovation, and the need for a mentorship program, Emily and Rebecca honestly paint a self-portrait that includes the influence of their past experiences before becoming a teacher and the reality of joining the profession of teaching. All administrators and educators should take note of Emily and Rebecca's tale in order for changes to be made that will create an environment that is encouraging and inviting for all teachers that will lead to teacher retention, and, in turn, focuses on the success for all students.
The State of Emergency: Police and Carceral Regimes in Modern Ethiopia

This article examines how Ethiopian governments have periodically declared a state of emergency in the country; these effectively turned out to be police and carceral regimes during periods of poli...
Thom H. Dunning, Jr.: Contributions to chemical theory and computing

Thom H. Dunning, Jr., provides an outstanding example of success in science, computing, and scientific leadership. From his scientific contributions to knowledge to his developments and accomplishments that have enabled discovery, Thom’s influence upon science, computing, and the scientific community has been significant.
Renal production of erythropoietin and renin after experimental kidney infarction.

IN previous experiments we have showrn that injection of plastic microspheres into a renal artery results in production of erythropoietin and reticulocytosis1 and development of hypertension2.
Post-Mao China: an alternative to ‘The end of history’?

Abstract The authoritarian regime in China emerged after Mao’s rule. It was successful not despite brutality, but precisely because of brutality. It was a regime policy that insured stability and provided economic growth and military buildup for the future. In the future generations, China could be stronger than the USA. The ideology of the regime was a successful blending of nationalism with Marxism. Unlike Russia, that followed the Western prescriptions and failed to pull itself from the crisis, post-Mao China is a viable alternative to Western liberal capitalism. At the same time, the success of China actually depends on one man—the leader.
A generalized visco-plasticity model and its algorithmic implementation

Abstract In this work we present a new rate-dependent model, which has the feature of being bounded by two plasticity models. After a brief review of the continuous equations for a material with inelastic behavior governed by a von Mises (J2) yield function, including both linear isotropic and kinematic hardening mechanisms, we introduce their discrete counterpart within the framework of a return mapping algorithm. Hence, we address the new material model, called generalized visco-plasticity, which includes as sub-cases classical visco-plasticity, classical plasticity and generalized plasticity. We discuss both the continuous and the discrete-time version for the case of a J2 associative model. Moreover, we present its algorithmic implementation in a return map setting as well as the form of the discrete consistent tangent tensor, which guarantees quadratic convergence in a Newton iterative technique. Finally, some numerical simulations are presented to illustrate the performance of the new material model.
Organic Nanocrystals of the Resorcinarene Hexamer via Sonochemistry: Evidence of Reversed Crystal Growth Involving Hollow Morphologies

Nano- and micrometer-scale crystals of a self-assembled hexamer have been synthesized via sonochemistry. The application of ultrasonic irradiation afforded hollow rhombic-dodecahedral crystals of the C-methylcalix[4]resorcinarene hexamer. The formation of the hollow crystals is attributed to a reversed crystal growth mechanism heretofore described only in the synthesis of inorganic-based materials.
The Synthesis and Purification of the Carbamoylmethylphosphine Oxides

ABSTRACT The details of the synthesis and purification of symmetrical and unsymmetrlcal carbamoylmethylphosphine oxides (CMPO 's) are described. The approaches used to provide a variety of substitution patterns around the two potential donor groups include the Arbusov, Michaelis-Becker and Grignard reactions. Several methods for purifying the extractants were studied. The use of acidic and basic ion exchange resins in conjunction was developed for the removal of acidic impurities which are very troublesome to the extraction performance of these compounds.
901–40 Gender-related Differences in Smooth Muscle Cell Proliferation in Response to Estradiol and Dihydrotestosterone

The cardioprotective effect of estradiol (E 2 ) is strongly supported by the reduced incidence of coronary artery disease (CAD) observed in premenopausal females versus age-matched males and in postmenopausal females on estrogen therapy. The favorable effect of estrogen on lipid profiles does not fully account for the observed cardiac benefits in females versus males. We have previously demonstrated that physiologic concentrations of E 2 inhibit female pig coronary vascular smooth muscle cells (VSMC) in vitro; this may partially account for estrogen's favorable cardiac effects. We determined the effect of sex steroids Idihydrotestosterone (DHT) and E 2 ) and tamoxifen Ian anti-estrogen) on proliferation of coronary VSMC obtained from male pigs. VSMC were cultured in phenol red-free Media 199 with 10% fetal calf serum. Cells obtained from mature adult male pigs were growth arrested in serum-free media for 24 hours, and treated with effectors in 2% charcoalstripped serum at concentrations ranging from 10 -11 to 10 -7 M for 24 hours. Cell proliferation was assessed by tritiated thymidine incorporation corrected for protein content. No significant effect on proliferation was observed in E 2 or tamoxifen-treated cells versus vehicle controls. Proliferation was significantly increased in cells treated with DHT at 10 -11 M. In conclusion, E 2 did not inhibit proliferation of coronary VSMC obtained from intact male animals, in contrast to the inhibition observed previously in VSMC obtained from intact female pigs. This gender-related differential response in vitro to E 2 may partially explain the reduction in CAD in estrogen-replete women compared to men. Tamoxifen had no effect on VSMC proliferation. The increased proliferation of VSMC in response to dihydrotestosterone may playa role in the pathogenesis of CAD in males.
How sexually dimorphic are we? Review and synthesis

The belief that Homo sapiens is absolutely dimorphic with the respect to sex chromosome composition, gonadal structure, hormone lev- els, and the structure of the internal genital duct systems and external geni- talia, derives from the platonic ideal that for each sex there is a single, universally correct developmental pathway and outcome. We surveyed the medical literature from 1955 to the present for studies of the frequency of deviation from the ideal male or female. We conclude that this frequency may be as high as 2% of live births. The frequency of individuals receiving "cor- rective" genital surgery, however, probably runs between 1 and 2 per 1,000 live births (0.1-0.2%). Am. J. Hum. Biol. 12:151-166, 2000. © 2000 Wiley-Liss, Inc.
3,8,11,16-Tetrakis(aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane tetra-trifluoroacetic acid: synthetic precursor to a novel thio-substituted diamine

Diamines have proven to be versatile intermediates in organic chemistry. Few diamines, however, can be appended to organic and inorganic supports without modification of the diamine functionality. We report the synthesis of 3,8,11,16-tetrakis-(N-BOC-aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane (2) and 3,8,11,16-tetrakis(aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane tetra-trifluoroacetic acid (3), potential precursors to 1,8-diamino-2,7-octanedithiol (4). Incorporation of the thiol units within the diamine backbone of 4 permits this compound to attach to organic and inorganic scaffolds. Spectral and chemical data showed that base hydrolysis of 1,8-bis(N-BOC-amino)-2,7-bis(acetylthio)octane (16) produced the 16-membered bis-disulfide 2 rather than the 8-membered ring dithiocane 17.
Responsiveness of the maximum time-varying elastance to alterations in left ventricular contractile state in man.

This investigation was designed to establish the relative responsiveness of maximum time-varying elastance (E,& slope values to alterations in left ventricular contractile state in comparison with isovolumic and ejection phase indices in man. Accordingly, nine patients had a bipolar right atrial pacing catheter and micromanometer left ventricular catheter placed and red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamic measurements and radionuclide angiograms were acquired simultaneously over a range of loading conditions produced by methoxamine or nitroprusside infusions during both the basal and enhanced contractile states. Enhanced left ventricular contractility was produced by a steady-state dobutamine infusion of 2 to 10 A/kg/min. The mean (+)dP/dt,,, increased from 1510 f 460 mm Hg/sec during the basal state to 2537 i 546 mm Hg/sec (p < 0.001) during the dobutamine infusion. The mean E,,, slope value also increased from 4.34 f 1.40 mm Hg/ml during the basal state to 6.41 + 1.90 mm Hg/ml (p < 0.001) during the dobutamine infusion. The average percent change in the E,,, slope value (51 +- 26%) was less than those for the isovolumic indices (57% to 112%), while it was more than those for the ejection phase indices (11% to 53%). When the variability in the percent changes for each of these contractile indices was incorporated into the analysis, the E,,, slope values demonstrated a greater responsiveness to changes in left ventricular contractility than did the isovolumic and ejection phase indices. In conclusion, the E,,, slope value calculated by this method is a contractile index, which is less affected by measurement variability and the influences of loading conditions than are the isovolumlc and ejection phase indices, and therefore may improve our ability to both detect and quantitate changes in left ventricular contractility in man. (AM HEART J 1989;118:1266.) Mark R. Starling, MD. Ann Arbor, Mich.
The Validity Generalization Model: An Approach to the Analysis of Validity Studies in Physical Education.

Abstract Validity generalization is a method of establishing the generalizability of the validity of a test by examining the results of all previous validity studies of the test of interest. In this paper, the validity generalization model was described and modified for application to concurrent validity studies of motor behavior. An example was provided using a small data set from selected studies of field tests of cardiorespiratory function. The model is recommended as an approach to clarifying the relationship between a test and a criterion measure in physical education and exercise science.
Reconstitution of adaptive and innate immunity following allogeneic hematopoietic stem cell transplantation in humans

Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment modality for a number of hematologic malignancies, as well as inherited immunodeficiencies and hemoglobinopathies, and may also have a role in selected acquired autoimmune disorders. The complete or near-complete ablation of host immunity and subsequent establishment of donor-derived immunity that is required for successful engraftment and long-term outcomes provide a major obstacle to such transplantation approaches. A delicate balance exists between the need for the reconstituted donor-derived immunity to provide both protection against pathogenic challenges and graft-versus-malignancy activity, and the potentially harmful expansion of alloreactive T-cell clones mediating GvHD. The search for interventions that would allow more rapid and selective reconstitution of beneficial immune specificities continues to be informed by the development of new tools enabling a more precise dissection of the kinetics of reconstituting populations. This review summarizes more recent data on immune reconstitution following allogeneic transplantation in humans.
How accurate is the label “allergic to iodinated contrast agents”?

BackgroundIodinated contrast agents (ICAs) are crucial to the use of many imaging studies. Reported allergies to ICAs in the medical record can interfere with optimal diagnostic imaging workups.Pur...
An integrated strategy for identification of both sharp and broad peaks from next-generation sequencing data

A novel integrative approach has been developed by Lieb and colleagues for analyzing genome-wide datasets of different chromatin-binding factors and epigenetic states that exhibit both sharp and diffuse signals on the genome.
Compact phase delay technique for increasing the amplitude of coherent population trapping resonances in open Λ systems

We propose and demonstrate a novel technique for increasing the amplitude of coherent population trapping (CPT) resonances in open Λ systems. The technique requires no complex modifications to the conventional CPT setup and is compatible with standard microfabrication processes. The improvement in the CPT resonance amplitude as a function of intensity of the excitation light agrees well with the theory based on ideal open and closed Λ systems.
The Autonomy‐Connection Challenge in Adolescent–Peer Relationships

The world of peers presents a unique developmental challenge to adolescents—one that is likely to be linked to prior experiences within the family, affected by concurrent experiences with adults outside the family, and predictive of future mental and physical health. To negotiate relationships with peers successfully, adolescents must manage the challenge of connecting with peers while establishing autonomy regarding peer influences. Both the nature of this challenge and how it is handled are linked closely to the ways adolescents are treated by the adults in their lives. Adolescents’ capacities for autonomy and connection can be developed both in the family and in interventions that engage youth with adults outside the family, suggesting a substantial role for adults in easing adolescents’ peer challenges.
Adaptive mode tuning for vibrational gyroscopes

We present an adaptive controller for tuning the natural frequency of the drive axis of a vibrational gyroscope. This is an attractive alternative to a phase-locked loop, since it introduces feedback, which can reduce the effects of imprecise fabrication. We also operate the gyroscope at a fixed frequency, chosen by the designer, which can simplify signal processing.
Infrared hyperspectral imaging using a broadly tunable external cavity quantum cascade laser and microbolometer focal plane array

A versatile mid-infrared hyperspectral imaging system is demonstrated by combining a broadly tunable external cavity quantum cascade laser and a microbolometer focal plane array. The tunable midinfrared laser provided high brightness illumination over a tuning range from 985 cm-1 to 1075 cm-1 (9.30–10.15 µm). Hypercubes containing images at 300 wavelengths separated by 0.3 cm-1 were obtained in 12 s. High spectral resolution chemical imaging of methanol vapor was demonstrated for both static and dynamic systems. The system was also used to image and characterize multiple component liquid and solid samples.
Soil CO2 flux and photoautotrophic community composition in high-elevation, 'barren' soil.

Summary Soil-dominated ecosystems, with little or no plant cover (i.e. deserts, polar regions, high-elevation areas and zones of glacial retreat), are often described as 'barren', despite their potential to host photoau- totrophic microbial communities. In high-elevation, subnival zone soil (i.e. elevations higher than the zone of continuous vegetation), the structure and function of these photoautotrophic microbial commu- nities remains essentially unknown. We measured soil CO2 flux at three sites (above 3600 m) and used molecular techniques to determine the composition and distribution of soil photoautotrophs in the Colo- rado Front Range. Soil CO2 flux data from 2002 and 2007 indicate that light-driven CO2 uptake occurred on most dates. A diverse community of Cyanobacte- ria, Chloroflexi and eukaryotic algae was present in the top 2 cm of the soil, whereas these clades were nearly absent in deeper soils (2-4 cm). Cyanobacte- rial communities were composed of lineages most closely related to Microcoleus vaginatus and Phor- midium murrayi, eukaryotic photoautotrophs were dominated by green algae, and three novel clades of Chloroflexi were also abundant in the surface soil. During the light hours of the 2007 snow-free measure- ment period, CO2 uptake was conservatively esti- mated to be 23.7 g C m -2 season -1 . Our study reveals that photoautotrophic microbial communities play an important role in the biogeochemical cycling of sub- nival zone soil.
Does reduction of the eggshell occur concurrently with or subsequent to the evolution of viviparity in phrynosomatid lizards

Viviparity and placentation have evolved many times within squamate reptiles, but the sequence in which the attendant morphological modifications occur remains unclear. In particular, it is unknown whether a reduction of the egg shell occurs concurrently with longer periods of egg retention (i.e. increasingly advanced stages of embryogenesis at oviposition) or whether such thinning occurs after viviparity has evolved. To investigate this question, we evaluated the prediction that shell morphology and permeability vary systematically with the capacity to support embryonic development in utero (as judged by the maximum embryonic stage attainable in utero) in five species of oviparous sceloporine lizards and one lizard species in the sister genus Urosuarus. Despite major differences among species in the capacity to support embryogenesis, shell morphology (structure, thickness) and physiology (permeability to water vapour) did not vary as predicted. These results raise the intriguing possibility that other features associated with simple placentation (e.g. increased oviductal and chorioallantoic vascular density) evolve concurrently with longer periods of egg retention and viviparity and that shell thinning may occur subsequent to the evolution of viviparity, at least in sceloporine lizards.
Spatial and temporal distributions of surface temperature and chlorophyll in the Gulf of Maine during 1998 using SeaWiFS and AVHRR imagery

Abstract The temporal and spatial distributions of SST and surface chlorophyll in northeastern coastal areas (46.0°N, 74.0°W to 40.0°N, 62.0°W) were examined using a year-long time series of composite SST and chlorophyll images during 1998. Five study areas were identified in these images: Gulf of Maine, Nantucket shoals/Georges Bank, Scotian shelf waters, slope water and coastal waters (depth
JMOCHA: a model checking tool that exploits design structure

Model checking is a practical tool for automated debugging of embedded software. In model checking, a high-level description of a system is compared against a logical correctness requirement to discover inconsistencies. Since model checking is based on exhaustive state-space exploration and the size of the state space of a design grows exponentially with the size of the description, scalability remains a challenge. We have thus developed techniques for exploiting modular design structure during model checking, and the model checker jMocha (Java MOdel-CHecking Algorithm) is based on this theme. Instead of manipulating unstructured state-transition graphs, it supports the hierarchical modeling framework of reactive modules. jMocha is a growing interactive software environment for specification, simulation and verification, and is intended as a vehicle for the development of new verification algorithms and approaches. It is written in Java and uses native C-code BDD libraries from VIS. jMocha offers: (1) a GUI that looks familiar to Windows/Java users; (2) a simulator that displays traces in a message sequence chart fashion; (3) requirements verification both by symbolic and enumerative model checking; (4) implementation verification by checking trace containment; (5) a proof manager that aids compositional and assume-guarantee reasoning; and (6) SLANG (Scripting LANGuage) for the rapid and structured development of new verification algorithms. jMocha is available publicly at ; it is a successor and extension of the original Mocha tool that was entirely written in C.
Identification of adult mineralized tissue zebrafish mutants.

Zebrafish craniofacial, skeletal, and tooth development closely resembles that of higher vertebrates. Our goal is to identify viable adult zebrafish mutants that can be used as models for human mineralized craniofacial, dental, and skeletal system disorders. We utilized a large-scale forward-genetic chemical N-ethyl-nitroso-urea (ENU) mutagenesis screen to identify 17 early lethal homozygous recessive mutants with defects in craniofacial cartilage elements, and 7 adult homozygous recessive mutants with mineralized tissue phenotypes including craniofacial shape defects, fused sutures, dysmorphic or missing skeletal elements, scoliosis, and neural arch defects. One mutant displayed both an early lethal homozygous phenotype and an adult heterozygous phenotype. These results extend the utility of the zebrafish model beyond the embryo, to study human bone and cartilage disorders.
Capping of vesicular stomatitis virus pre-mRNA is required for accurate selection of transcription stop–start sites and virus propagation

The multifunctional RNA-dependent RNA polymerase L protein of vesicular stomatitis virus catalyzes unconventional pre-mRNA capping via the covalent enzyme-pRNA intermediate formation, which requires the histidine–arginine (HR) motif in the polyribonucleotidyltransferase domain. Here, the effects of cap-defective mutations in the HR motif on transcription were analyzed using an in vitro reconstituted transcription system. The wild-type L protein synthesized the leader RNA from the 3′-end of the genome followed by 5′-capped and 3′-polyadenylated mRNAs from internal genes by a stop–start transcription mechanism. Cap-defective mutants efficiently produced the leader RNA, but displayed aberrant stop–start transcription using cryptic termination and initiation signals within the first gene, resulting in sequential generation of ∼40-nucleotide transcripts with 5′-ATP from a correct mRNA-start site followed by a 28-nucleotide transcript and long 3′-polyadenylated transcript initiated with non-canonical GTP from atypical start sites. Frequent transcription termination and re-initiation within the first gene significantly attenuated the production of downstream mRNAs. Consistent with the inability of these mutants in in vitro mRNA synthesis and capping, these mutations were lethal to virus replication in cultured cells. These findings indicate that viral mRNA capping is required for accurate stop–start transcription as well as mRNA stability and translation and, therefore, for virus replication in host cells.
Seed size- and density-related hidden treatments in common biodiversity experiments

Aims With a few exceptions, most well-known field biodiversity experiments on ecosystem functioning have been conducted in plant communities (especially grasslands) in which different numbers of species are planted as treatments. In these experiments, investigators have either kept the total seed weight or seed number constant across treatment plots. However, although in some cases attempts have been made to randomly choose species for planting from a designated species pool, the issue of possible ‘hidden treatments’ remains unsolved. Particularly, the total and relative abundance among species and across treatments could still affect the results. This study aims to determine whether treatments related to planted seed abundance and seed size may contribute to observed productivity. Methods We re-analyzed data from four biodiversity experiments based on
Gender, Grade Point Average, and Test Anxiety

The present study assessed the effect of gender on test anxiety and grade point average (GPA) among 40 college students. Subjects reported their GPAs and responded to a test-anxiety questionnaire. Analysis of covariance indicated that gender did not affect GPA after an adjustment was made for differences in test anxiety. However, gender produced a significant effect on test anxiety following an adjustment for GPA differences, with women reporting significantly more test anxiety than men. The results were discussed in terms of anxiety's motivating capabilities.
Improved ethanol yield and reduced Minimum Ethanol Selling Price (MESP) by modifying low severity dilute acid pretreatment with deacetylation and mechanical refining: 1) Experimental

Background Historically, acid pretreatment technology for the production of bio-ethanol from corn stover has required severe conditions to overcome biomass recalcitrance. However, the high usage of acid and steam at severe pretreatment conditions hinders the economic feasibility of the ethanol production from biomass. In addition, the amount of acetate and furfural produced during harsh pretreatment is in the range that strongly inhibits cell growth and impedes ethanol fermentation. The current work addresses these issues through pretreatment with lower acid concentrations and temperatures incorporated with deacetylation and mechanical refining.
Ultrasound Imaging of Scrotal Wall Thizckening and Its Significance in the Diagnosis of Fournier's Cangrene in Older Men

Scrotal sonograms of a series of older patients with scrotal wall thickening were analyzed retrospectively for associated sonographic, radiographic, and clinical features. Scrotal thickening in debilitated, older men can be a sign of more grave pathology and may be associated with a significant morbidity.
Five Best Resources for Developing Multicultural Competence.

When I began teaching in a seminary over twelve years ago, I was a fairly experienced teacher. I was committed to inclusive teaching practices, but I quickly learned that I had much to learn. Nothi...
Mucosal lesions and mortality associated with the use of a ferric sulfate poultry litter amendment product

Within hours of chick delivery, acute mortality and mucosal lesions were reported on 2 northeast Georgia broiler farms that had applied a ferric sulfate litter amendment product. Histological evaluation of the larynx, tongue, and surrounding stroma revealed multifocal areas of necrosis or degeneration of the oral mucosa, acute focal necrotizing cellulitis, and the presence of a brown-black pigmented material adhered to affected epithelial and mucosal surfaces. Multifocal to diffuse ventricular koilin degeneration and acute hemorrhage was also demonstrated in association with pigmented adherent material on affected surfaces. Perls iron stain revealed that adherent material on affected tissues was strongly positive for iron. An experiment was designed to reproduce clinical signs, lesions, and mortality using the same litter amendment product. The ferric sulfate litter amendment was confirmed as the causative agent.
Cytokine-effects on glucocorticoid receptor function : Relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression

Glucocorticoids play an essential role in the response to environmental stressors, serving initially to mobilize bodily responses to challenge and ultimately serving to restrain neuroendocrine and immune reactions. A number of diseases including autoimmune, infectious and inflammatory disorders as well as certain neuropsychiatric disorders such as major depression have been associated with decreased responsiveness to glucocorticoids (glucocorticoid resistance), which is believed to be related in part to impaired functioning of the glucocorticoid receptor (GR). Glucocorticoid resistance, in turn, may contribute to excessive inflammation as well as hyperactivity of corticotropin releasing hormone and sympathetic nervous system pathways, which are known to contribute to a variety of diseases as well as behavioral alterations. Recent data indicate that glucocorticoid resistance may be a result of impaired GR function secondary to chronic exposure to inflammatory cytokines as may occur during chronic medical illness or chronic stress. Indeed, inflammatory cytokines and their signaling pathways including mitogen-activated protein kinases, nuclear factor-kB, signal transducers and activators of transcription, and cyclooxygenase have been found to inhibit GR function. Mechanisms include disruption of GR translocation and/or GR-DNA binding through protein-protein interactions of inflammatory mediators with the GR itself or relevant steroid receptor cofactors as well as alterations in GR phosphorylation status. Interestingly, cAMP signal transduction pathways can enhance GR function and inhibit cytokine signaling. Certain antidepressants have similar effects. Thus, further understanding the effects of cytokines on GR signaling and the mechanisms involved may reveal novel therapeutic targets for reversal of glucocorticoid resistance and restoration of glucocorticoid-mediated inhibition of relevant bodily/immune responses during stress and immune challenge.
Prenatal Decision-Making for Myelomeningocele: Can We Minimize Bias and Variability?

* Abbreviations: AAP — : American Academy of Pediatrics ACOG — : American College of Obstetricians and Gynecologists MMCTF — : Myelomeningocele Maternal-Fetal Management Task Force convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development MOMS — : Management of Myelomeningocele Study Prenatal decision-making for myelomeningocele changed in 2011, when MOMS (Management of Myelomeningocele Study) demonstrated the effectiveness of intrauterine fetal surgery, thereby securing this intervention as an alternative to either pregnancy termination or postnatal repair.1 Although it is hoped that an evidence-based approach to medical decisions using the MOMS results would improve the quality of information received by pregnant patients, we believe that unless specific steps are taken, prenatal counseling for myelomeningocele (counseling that occurs in myriad locations across the United States) will be persistently marred by hidden biases and excess variability. We believe this prenatal counseling will be affected for 3 reasons. First, the MOMS results present tradeoffs. Rates of ventriculoperitoneal shunt placement and ambulation were improved for children who underwent prenatal repair but with higher rates of prematurity and respiratory distress syndrome, as well as important maternal complications. Adding to the uncertainty, long-term outcomes are unavailable; prognosis remains difficult to predict for any given fetus; and posttrial complication rates reportedly differ from trial results, with higher rates of perinatal death (6% vs 3%) and respiratory distress syndrome (52% vs 21%) but fewer maternal complications (pulmonary edema, 2% vs 6%; maternal transfusion, 3.4% vs 9%).1 Women undergoing intrauterine surgery require cesarean deliveries for all future pregnancies. The reasoning regarding such multifaceted risk/benefit tradeoffs for obstetric and neonatal interventions is notably difficult for both physicians and patients.2 Second, physicians commonly have differing opinions regarding … Address correspondence to Stephen D. Brown, MD, Department of Radiology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: stephen.brown{at}childrens.harvard.edu
Maternal death review in Africa.

Abstract Objective WHO, UNICEF, and UNFPA with other development partners have supported African Ministries of Health to institutionalize maternal death review (MDR) since 2003. To evaluate the program, its status, lessons learned, and the challenges to success were reviewed in 2007. Methods A standard self-administered questionnaire was sent to Ministries of Health in 46 Sub-Saharan African countries in May 2007. Completed questionnaires were returned by e-mail, processed, and analyzed. Results Thirty countries completed the survey questionnaire. Maternal death is a notifiable condition in 21 (67%) counties. A national committee has been set up to plan, coordinate, and implement MDR activities in 7 countries. Fifteen countries stated that facility-based MDR is the main method selected for conducting reviews of the causes of maternal death. Fourteen (47%) countries reported that national MDR guidelines had been developed and 12 (40%) had implemented the guidelines. Fifteen (50%) countries reported that maternal deaths were reviewed and analyzed. Only 7 countries reported that the government had allocated a budget for MDR. Implementation of MDR has led to local policy changes and improvement in quality of maternal health services in several countries. Ten of the 15 countries in which analysis has been conducted reported that recommendations have been implemented at least at the health facility level. Conclusion Although use of MDR is increasing in African countries, effective coverage is still low. The institutionalization of MDR requires political commitment, legal and administrative back-up, financial support, capacity development, simplified reporting forms and procedures, coordinated support of development partners, involvement of professional bodies, and regular supportive follow-up.
Lifetimes of Excited Alkalilike Atoms Colliding by Van der Waals Forces with Inert Gas Atoms in the Groundstate

The influence of Van der Waals forces on the lifetime of coherently excited hyperfine-states |FimFi〉 and |FimFi〉 of alkalilike atoms i by collissions with inert gas atoms j in the groundstate |FjmFi〉 has been examined. To do this the timedependent Schrodinger equation has been solved on taking into account a static magnetic field, a radiation field and a Van der Waals force. Introducing an impact parameter model for the colliding atoms with small scattering angles which form a quasimolecule |μ〉 = |FimFiFjmFi 〉 an expression for the cross section σμμ has been derived which determines the halfwidth Γ μμ of the coherently excited states. On making use of the irreducible tensor representation the calculation of the cross-section has been reduced to the calculation of multipole transitions. The result has been applied e. g. to the coherently excited 3d104p2P3/2-states of Cu I colliding by dipole-dipole interaction with inert gas atoms He I, and Ar I in the ground state. The values agree well with data which have been derived from zero-level-crossing experiments.
Substitution of herpes simplex virus 1 entry glycoproteins with those of saimiriine herpesvirus 1 reveals a gD-gH/gL functional interaction and a region within the gD profusion domain that is critical for fusion

ABSTRACT To gain insight into the mechanism of herpesvirus entry into cells, the four glycoproteins that are necessary for herpes simplex virus (HSV) fusion were cloned from the saimiriine herpesvirus 1 (SaHV-1) genome, a primate member of the alphaherpesvirus family. Cell-cell fusion assays indicate that SaHV-1 entry glycoproteins function with the previously identified alphaherpesvirus entry receptors nectin-1 and CD155 but not with herpesvirus entry mediator (HVEM) or paired immunoglobulin-like type 2 receptor alpha (PILRα). Replacement of HSV-1 gD with the SaHV-1 gD homolog resulted in a complete loss of fusion function when coexpressed with HSV-1 gB and gH/gL. HSV-1 gD was also unable to substitute for SaHV-1 gD when coexpressed with SaHV-1 gB and gH/gL. Similarly, the gH/gL heterodimers from HSV-1 and SaHV-1 were not interchangeable. In contrast, both the HSV-1 and SaHV-1 gB homologs retained function in a heterotypic context. These results suggest that an essential interaction between homotypic gD and gH/gL occurs during both HSV-1 and SaHV-1 entry. To map the site of this homotypic interaction, we created a series of gD chimeras, focusing on the “profusion domain” (PFD) that consists of HSV-1 gD residues 261 to 305 or SaHV-1 gD residues 264 to 307. We identified a seven-amino-acid stretch (264 RTLPPPK 270) at the N terminus of the SaHV-1 gD PFD that contributes to homotypic fusion. Finally, we found that the gD receptor-binding region and PFD cannot function independently but that both can inhibit the function of wild-type gD. IMPORTANCE The herpesvirus entry machinery requires the concerted action of at least four glycoproteins; however, details of the interactions among these glycoproteins are not well understood. Like HSV-1, SaHV-1 belongs to the alphaherpesvirus subfamily. Using cell-cell fusion experiments, we found that SaHV-1 uses the entry receptors nectin-1 and CD155 but not HVEM or PILRα. By swapping the entry glycoproteins between HSV-1 and SaHV-1, we revealed a functional interaction between gD and gH/gL. To examine the homotypic interaction site on gD, we evaluated the function of a panel of HSV-1/SaHV-1 gD chimeras and identified a small region in the SaHV-1 gD profusion domain that is critical for SaHV-1 fusion. This study contributes to our understanding of the molecular mechanisms of herpesvirus entry and membrane fusion.
Supporting event based traceability through high-level recognition of change events

Although requirements traceability is crucial in both the development and maintenance of a software system, traceability links and related artifacts tend to deteriorate, as time-pressured practitioners fail to systematically update them in response to change. Event-based traceability addresses this issue by establishing links through a loosely coupled publisher/subscriber scheme. Dependent entities subscribe to requirements and receive event notifications as changes occur. This paper focuses upon the role played by the requirements specification as a publisher of events. A set of standard change events is defined and a method for monitoring a user's actions within a requirements management environment and the subsequent recognition and publication of the change events is proposed. Early results obtained from testing this approach are reported.
Parent Expectations Mediate Outcomes for Young Adults with Autism Spectrum Disorder

Understanding the complex relationships among factors that may predict the outcomes of young adults with autism spectrum disorder (ASD) is of utmost importance given the increasing population undergoing and anticipating the transition to adulthood. With a sample of youth with ASD (n = 1170) from the National Longitudinal Transition Study-2, structural equation modeling techniques were used to test parent expectations as a mediator of young adult outcomes (i.e., employment, residential independence, social participation) in a longitudinal analysis. The mediation hypothesis was confirmed; family background and functional performance variables significantly predicted parent expectations which significantly predicted outcomes. These findings add context to previous studies examining the role of parent expectations on young adult outcomes and inform directions for family-centered interventions and future research.
Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial-mesenchymal transition

Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241-5253). We investigated the mechanisms by which SPRY regulates epithelial-mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3' untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1(-/-) and Spry2(-/-) double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.
Structure-Activity Relationships of the Quinolone Antibacterials in the New Millennium: Some Things Change and Some Do Not

The review by Domagala in 1994 represented one of the first attempts to simultaneously delineate the structure-activity relationships (SARs) of both activity and side effects providing some insights as to where the future of the quinolones might reside. A significant conclusion of this work was that the side chain at C-7 in conjunction with that at C-8 would be the main focus of successful quinolone manipulation; all other positions were viewed as optimal. The chiral form of the fluorocyclopropyl group slightly affects the overall antibacterial activity, with a two- to four-fold difference in potency between the most active stereoisomer and the least active; overall, the cis isomer was more efficacious than the trans isomer. The 2 pyridones, which were introduced in 1994, represent a new structural class of "quinolone-type" antibacterials. The fluoroquinolones derived their name from the dogma that the 6-fluoro group was an essential feature of the broad-spectrum quinolones that first appeared in the late 1970s. Extensive SAR work on 7-(3-amino)-azetidinyl quinolones such as E-4695 (structure 35) has been reported. Initial success with the 3-amino derivatives led to further exploration of 2-alkyl-3-amino analogs (structure 36) with particular emphasis on the effects of stereochemistry on antibacterial activity. The reality of the quinolone SAR efforts is that all the potency ever required was already in hand in the early 1990s.
Adenosine Stimulation of DNA Synthesis in Mammary Epithelial Cells

AbstractAdenosine increased the DNA synthesis rate and the percentage of S-phase cells 2–3-fold in mouse mammary epithelial cells (NMuMG), with an optimum concentration of 10–100 μM. This effect was not mimicked by adenosine metabolites adenine, hypoxanthine, or inosine. N-ethylcarboxamidoadenosine (NECA, a relatively nonselective adenosine receptor agonist) and 2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarbox-amidoadenosine (CGS-21680, an A2 selective agonist) also increased DNA synthesis by mammary epithelial cells. However, N6-cyclohexyladenosine (CHA, an agonist for A1 type receptors) decreased DNA synthesis. The A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) had no effect on basal or adenosine-induced DNA synthesis, whereas the A2 selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) decreased adenosine-induced DNA synthesis. Similar effects were observed in another nontumorigenic mouse mammary epithelial line, HC11, as well as the nontumorigenic human lines MCF-10A and...
Electron Cryo-Tomography of Nanowires in Shewanella Oneidensis MR-1

The dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 is known to make ‘nanowires,’ conductive cell appendages used in electron transport. Novel live fluorescence imaging techniques recently clarified that the conductive filaments in S. oneidensis are not pili, as previously thought, but rather extensions of the outer membrane. However, their fine structure and mechanism remained unclear. Here, we report the first high-resolution in vivo images of nanowires in frozen-hydrated cells in a near-native state by electron cryo-tomography (ECT). We first developed a method for in vivo production of nanowires in cells grown on EM grids. Using correlative light microscopy and ECT, we then identified and imaged nanowires at high resolution and in three dimensions. Interestingly, we find that nanowires are composed of outer membrane vesicles (OMVs) strung together to form a chain. The size of the vesicles and the length and thickness of the vesicle chain are highly variable. However, even apparently smooth filaments such as those described previously are in fact, at higher resolution, revealed to be chains of OMVs. This work will help us investigate the electron transport mechanism along Shewanella nanowires. Additionally, this work has implications in understanding how OMVs, ubiquitous in Gram-negative bacteria, can assemble into chains.