cssi/SciSciGPT-SciSciNet huggingface dataset:
Fenretinide Perturbs Focal Adhesion Kinase in Premalignant and Malignant Human Oral Keratinocytes. Fenretinide's Chemopreventive Mechanisms Include ECM Interactions.

The membrane-associated protein, focal adhesion kinase (FAK), modulates cell–extracellular matrix interactions and also conveys prosurvival and proliferative signals. Notably, increased intraepithelial FAK levels accompany transformation of premalignant oral intraepithelial neoplasia (OIN) to oral squamous cell carcinoma (OSCC). OIN chemoprevention is a patient-centric, optimal strategy to prevent OSCC9s comorbidities and mortality. The cancer chemopreventive and synthetic vitamin A derivative, fenretinide, has demonstrated protein-binding capacities, for example, mTOR- and retinol-binding protein interactions. These studies used a continuum of human oral keratinocytes (normal-HPV E6/E7-transduced-OSCC) to assess potential fenretinide–FAK drug protein interactions and functional consequences on cellular growth regulation and motility. Molecular modeling studies demonstrated that fenretinide has approximately 200-fold greater binding affinity relative to the natural ligand (ATP) at FAK9s kinase domain. Fenretinide also shows intermediate binding at FAK9s FERM domain and interacts at the ATP-binding site of the closest FAK analogue, PYK2. Fenretinide significantly suppressed proliferation via induction of apoptosis and G 2 –M cell-cycle blockade. Fenretinide-treated cells also demonstrated F-actin disruption, significant inhibition of both directed migration and invasion of a synthetic basement membrane, and decreased phosphorylation of growth-promoting kinases. A commercially available FAK inhibitor did not suppress cell invasion. Notably, although FAK9s FERM domain directs cell invasion, FAK inhibitors target the kinase domain. In addition, FAK-specific siRNA–treated cells showed an intermediate cell migration capacity; data which suggest cocontribution of the established migrating-enhancing PYK2. Our data imply that fenretinide is uniquely capable of disrupting FAK9s and PYK2′s prosurvival and mobility-enhancing effects and further extend fenretinide9s chemopreventive contributions beyond induction of apoptosis and differentiation. Cancer Prev Res; 8(5); 419–30. ©2015 AACR .
Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice

Theiler's virus induces immune-mediated demyelinating disease similar to human MS in susceptible mice. Though the MHC class II-restricted T cell response is critical, susceptibility/resistance is also associated with a MHC class I haplotype. Here we report that perforin-deficient C57BL/6 mice (pKO) are susceptible to demyelination and develop clinical disease. The levels of primary demyelination, proliferation, Th1 responses, and viral load were also markedly enhanced. In addition, immunization of pKO mice with UV-inactivated virus further enhanced clinical incidence and accelerated the disease course. Thus, perforin is most likely involved in viral clearance, hence protection from the disease.
Report impaired practice--stat.

Don't hesitate to report substance abuse and mental illness-doing so often initiates the treatment process for valued staff.
Experimental Justice Random Judicial Assignment and the Partisan Process of Supreme Court Review

This study utilizes the random assignment of judges to panels in the U.S. courts of appeals to measure how the partisanship of these judges affects whether or not the Supreme Court agrees to hear a...
Flux across nonsmooth boundaries and fractal Gauss/Green/Stokes' theorems

By replacing the parametrization of a domain with polyhedral approximations we give optimal extensions of theorems of Gauss, Green and Stokes'. Permitted domains of integration range from smooth submanifolds to structures that may not be locally Euclidean and have no tangent vectors defined anywhere. One may still calculate divergence and curl over a domain, and flux across its boundary which itself may have no normal vectors defined anywhere.
Effects of feeding schedules on diurnal periodicity of Leucocytozoon smithi gametocytes in the peripheral blood of domestic turkeys.

Eighteen domestic turkeys naturally infected with Leucocytozoon smithi Laveran & Lucet were maintained on restricted feeding schedules under conditions of either continuous light or natural light (light 13 h:darkness 11 h) photoperiods. Peripheral gametocyte numbers of L. smithi in all turkeys were determined every 2 h over a 36-h period. Peripheral gametocyte numbers of turkeys maintained under continuous light and restricted to either a 10-h feeding period (9:30 p.m. to 7:30 a.m.) once a day or a 2-h feeding period twice a day (7:30 a.m. to 9:30 p.m. and 7:30 p.m. to 9:30 p.m.) increased at or near the time of feed availability. Under natural photoperiod, gametocyte periodicity was not affected by restricting feed availability to the dark phase of the light-dark cycle. Mean parasite numbers were highest during the light phase when feed was not available, and lowest during the dark period when feed was accessible.
Dihydroorotic Acid Dehydrogenase Activity of Human Diploid Cell Strains

A gene affecting the final two enzymes of uridylic acid biosynthesis does not affect a third, metabolically adjacent enzyme. Similarly, compounds that increase cellular activity for the affected enzymes do not increase activity for the third enzyme. The pyrimidine pathway can be subdivided into groups of concurrently responding enzymes. These groups may be smaller in human cells than they are in microbial cells.
Gathering Interstellar Gas

Our solar system is plowing through the gas and dust that resides between the stars, the interstellar medium. The result is a bullet-shaped structure surrounding the Sun—called the heliosphere—that demarcates the balance between the outward pressure of the solar wind and the inward pressure of the surrounding gas. Every day, the heliosphere encounters a mass equivalent to Mount Everest, of what is often referred to as empty space, but which actually consists of atoms (mostly hydrogen), molecules, and dust. Some of that material is trapped at the nose of the heliosphere, some is diverted around it, and some passes right through it. On page 1291 of this issue, McComas et al. ( 1 ) present a new view of the heliosphere based on recent measurements by instruments onboard the Interstellar Boundary Explorer (IBEX) spacecraft ( 2 ) of those interstellar atoms that have passed through the heliosphere and traveled into the inner solar system.
EFFECT OF FOODSERVICE COOKERY METHOD, MARINATION, PORTION SIZE, AND ENDPOINT COOKING TEMPERATURE ON COOKING CHARACTERISTICS AND TENDERNESS OF PORK LOIN CHOPS1

There is an increased use of rapid cookery systems (e.g. Clamshell®) in the foodservice sector to decrease preparation time. Foodservice pork loin chops (n=320) were used to determine the effects of cookery method (Clamshell®, CS vs Farberware, FB), marination (marinated vs nonmarinated), portion size (113 vs 170 g), and endpoint cooking temperature (68 vs 75C) on cooking characteristics, shear force values and sensory traits. The first experiment (n = 160 chops) evaluated Warner-Bratzler shear force, while the second experiment (n = 160 chops) measured sensory traits and both measured cooking characteristics. The chops cooked by CS had shorter (P 0.05). Marination increased (P < 0.05) thaw loss. Cook times were shorter (P < 0.01) and thaw and cook losses were lower (P < 0.05) for 113 g compared to 170 g chops. The 113 g portions were more (P < 0.05) tender and juicy than 170 g. Chops cooked to 68C required less (P < 0.05) cooking time, and had lower (P < 0.05) cook losses than chops cooked to 75C. Marinated 113 g chops were significantly juicier than any other combination of marination and portion size. These data suggest that a rapid cookery system can reduce cooking time of foodservice pork loin chops by as much as 50%, without detrimental effects on eating quality.
Conservation tillage and input use

There continues to be a question as to the overall effectiveness of conservation tillage practices in reducing the impact of agricultural production on the environment. While it is generally recognized that water runoff and soil erosion will decline further, as tillage and mulch tillage systems are not used more extensively on cropland, what will happen to pesticide and fertilizer use remains uncertain. To gain some insight into this, the conservation tillage adoption decision is modelled. On the assumption that the decision to adopt conservation tillage is a two-step procedure, the first decision is whether or not to adopt a conservation tillage production system and the second concerns the extent to which conservation tillage should be used – appropriate models of the Cragg and Heckman (dominance) type are estimated. Based on farm-level data on corn production in the United States for 1987, the profile of a farm on which conservation tillage was adopted is that the cropland had above-average slope and experienced above-average rainfall, the farm was a cash grain enterprise, and it had an above-average expenditure on pesticides and a below-average expenditure on fuel and custom pesticide applications. Additionally, for a farm adopting a no-tillage production practice, an above-average expenditure was made on fertilizer.
Joint solution to fuzzy programming problems

We propose a new solution concept for fuzzy programming problems. It is based on our new method of solving fuzzy equations [ 101. For simplicity we discuss in detail only fuzzy linear programming in this paper. We define, and obtain the basic properties of the joint solution (a fuzzy vector in Rn and the optimal value of the objective function (a fuzzy number). Three examples are presented illustrating these concepts.
Seasonal Variations of the Earth's Gravitational Field: An Analysis of Atmospheric Pressure, Ocean Tidal, and Surface Water Excitation

Monthly mean gravitational field parameters (denoted here as C(sub even)) that represent linear combinations of the primarily even degree zonal spherical harmonic coefficients of the Earth's gravitational field have been recovered using LAGEOS I data and are compared with those derived from gridded global surface pressure data of the National meteorological center (NMC) spanning 1983-1992. The effect of equilibrium ocean tides and surface water variations are also considered. Atmospheric pressure and surface water fluctuations are shown to be the dominant cause of observed annual C(sub even) variations. Closure with observations is seen at the 1sigma level when atmospheric pressure, ocean tide and surface water effects are include. Equilibrium ocean tides are shown to be the main source of excitation at the semiannual period with closure at the 1sigma level seen when both atmospheric pressure and ocean tide effects are included. The inverted barometer (IB) case is shown to give the best agreement with the observation series. The potential of the observed C(sub even) variations for monitoring mass variations in the polar regions of the Earth and the effect of the land-ocean mask in the IB calculation are discussed.
Improving Drug Safety Surveillance Lessons From Rosiglitazone

The thiazolidinediones (TZDs) were introduced to the US market in 1997 as therapies to control hyperglycemia in patients with diabetes mellitus. This class of drugs (agonists of peroxisome proliferator-activated receptor γ) has a wide range of biochemical effects, including lowering blood sugar by increasing insulin sensitivity. The TZDs were adopted relatively rapidly and achieved sales of nearly $3 billion in the United States in 2009. Article see p 538 Rapid increases in TZD use occurred despite accumulating safety concerns about the drugs. The first in the class troglitazone was withdrawn from the US market in 2000 because of evidence that it could cause hepatotoxicity that was in some cases lethal. Subsequently, reports emerged that the 2 remaining TZDs available in the United States (pioglitazone and rosiglitazone, both approved in 1999) were associated with substantially higher risks of fluid retention and heart failure, complications of particularly serious consequence in patients with diabetes.1 However, TZD use remained robust, including among patients with important contraindications.2 Further, the 2 currently available TZDs have varied metabolic effects beyond lowering blood glucose, raising questions about their effects on important cardiovascular outcomes. Both agents modestly lower blood pressure but also cause weight gain and raise low-density lipoprotein cholesterol levels. Further, rosiglitazone significantly raises triglyceride and low-density lipoprotein cholesterol more than pioglitazone.3 Hypotheses about the impact of these metabolic effects on health outcomes were merely speculation until larger clinical studies became available. The cardiovascular effects of pioglitazone were studied in the Prospective Pioglitazone Clinical Trial in Macrovascular Events, a placebo-controlled clinical trial. Although the study had negative findings with respect to the primary composite cardiovascular outcome, a principal secondary end point of death and selected cardiovascular outcomes was significantly improved in patients receiving pioglitazone.4 Although this study was considered by many as inadequate evidence …
Biogeochemical environments of streambed-sediment pore waters with and without arsenic enrichment in a sedimentary rock terrain, New Jersey Piedmont, USA

Abstract Release of arsenic (As) from sedimentary rocks has resulted in contamination of groundwater in aquifers of the New Jersey Piedmont Physiographic Province, USA; the contamination also may affect the quality of the region's streamwater to which groundwater discharges. Biogeochemical mechanisms involved in the release process were investigated in the streambeds of Six Mile Run and Pike Run, tributaries to the Millstone River in the Piedmont. At Six Mile Run, streambed pore water and shallow groundwater were low or depleted in oxygen, and contained As at concentrations greater than 20 μg/L. At Pike Run, oxidizing conditions were present in the streambed, and the As concentration in pore water was 2.1 μg/L. The 16S rRNA gene and the As(V) respiratory reductase gene, arrA, were amplified from DNA extracted from streambed pore water at both sites and analyzed, revealing that distinct bacterial communities that corresponded to the redox conditions were present at each site. Anaerobic enrichment cultures were inoculated with pore water from gaining reaches of the streams with acetate and As(V). As(V) was reduced by microbes to As(III) in enrichments with Six Mile Run pore water and groundwater, whereas no reduction occurred in enrichments with Pike Run pore water. Cloning and sequencing of the arrA gene indicated 8 unique operational taxonomic units (OTUs) at Six Mile Run and 11 unique OTUs at Pike Run, which may be representative of the arsenite oxidase gene arxA. Low-oxygen conditions at Six Mile Run have favored microbial As reduction and release, whereas release was inhibited by oxidizing conditions at Pike Run.
Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma: correlation with prognosis.

Background The bcl-2 family of proteins are important regulators of apoptosis. Some of the members, such as bcl-2 and bcl-x(L), inhibit cell death, whereas others, such as bax and bcl-x(S), promote cell death. We evaluated the ratios of bcl-2:bax and bcl-2:bcl-x expression by image cytometry in invasive breast carcinoma to determine prognostic significance. Design Five-micron sections of formalin-fixed, paraffin-embedded tissue from 88 invasive breast carcinomas were immunostained using steam antigen retrieval, an avidin biotin-complex technique with automated stainer and primary antibodies against bcl-2 (1/160; Dako, Carpenteria, CA), bax (1/1,500; PharMingen, San Diego, CA), and bcl-x (1/1,500; PharMingen). Positive controls were tonsil (bcl-2) and normal breast (bax and bcl-x) tissue samples. Immunostain was measured in 15 high power fields as percentage positive area (PPA) in nuclei and cytoplasm using the CAS 200 image analyzer (Becton Dickinson, San Jose, CA). Results Median follow-up was 105 months (range 11-130). Significantly improved disease-free survival was found in patients with a bcl-2:bcl-x ratio > or = 1 by univariate and multivariate analyses. The bcl-2:bax ratio was not predictive of overall or disease-free survival. A significant difference in overall and disease-free survival was found between carcinomas with positive and negative bcl-2 expression by univariate analysis; by multivariate analysis, bcl-2 expression was an independent prognostic factor for disease-free survival. The 5-year survival rates were 77% and 50% in patients with bcl-2-positive and bcl-2-negative carcinomas, respectively. Conclusion A bcl-2:bcl-x ratio > or = 1, assessed by image cytometry, is significantly associated with improved disease-free survival in patients with invasive breast carcinoma. Significantly increased overall and disease-free survival is associated with positive bcl-2 expression.
Assignment of Human Myocyte-Specific Enhancer Binding Factor 2C (hMEF2C) to Human Chromosome 5q14 and Evidence That MEF2C Is Evolutionarily Conserved

Human myocyte-specific enhancer binding factor 2C (hMEF2C) belongs to the MEF2 subfamily of the MADS (MCM1, AGAMOUS, DEF A, serum response factor) family of transcription factors. Members of the MADS family share a conserved domain - the MADS domain - that is necessary for DNA binding. Highly conserved versions of the MADS domain and of an adjacent domain that is known as the MEF2 domain are found in members of the MEF2 subfamily. Both of these domains are necessary for binding to the MEF2 regulatory element. This regulatory element is known to be functionally important in a variety of muscle-specific genes and possibly in the brain creatine kinase gene. The MEF2C gene product activates transcription by binding to the MEF2 element. hMEF2C is expressed at high levels in postmitotic neurons in the brain, where it is most abundant in the cerebral cortex, and is also expressed in differentiated myotubes. Several lines of evidence suggest the existence of a rat homologue of MEF2C, and a mouse homologue has been cloned. The mouse gene was mapped to mouse chromosome 13 in a region that is syntenic to human 5q13-q15. 12 refs., 1 fig.
The absorption coefficient of the liquid N2 2.15-μm band and application to triton

The present measurements of the temperature dependence exhibited by the liquid N2 2.15-micron 2-0 collision-induced band's absorption coefficient and integrated absorption show the latter to be smaller than that of the N2 gas, and to decrease with decreasing temperature. Extrapolating this behavior to Triton's nominal surface temperature yields a new estimate of the N2-ice grain size on the Triton south polar cap; a mean N2 grain size of 0.7-3.0 cm is consistent with grain growth rate calculation results.
Chlorothalonil and chlorpyrifos degradation products in golf course leachate.

Chlorothalonil and chlorpyrifos are commonly used to control disease and insect pests on golf course greens. While they are relatively immobile in the soil profile, their respective soil degradation products, 4-hydroxy-2,5,6-trichloroisophthalonitrile and 3,5,6-trichloropyridin-2-ol are more polar and may be present in golf course green leachate. To investigate this possibility, six stainless steel lysimeters were constructed into two practice greens at a country club in a northern Atlanta, Georgia suburb. Over a period of 1 year after rainfall events, lysimeter leachate samples were collected into glass bottles, filtered and directly analyzed by HPLC with UV detection. Chlorpyrifos was not detected in any sample and chlorothalonil was detected only in one sample, at a concentration of 0.12 mg liter−1. With a limit of quantitation of 0.05 mg liter−1, hydroxychlorothalonil and trichloropyridinol were detected in 87% and 63% of the samples at maximum and median concentrations of 2.21 and 0.55 mg liter−1 for hydroxychlorothalonil and 1.77 and 0.15 mg liter−1 for trichloropyridinol. Golf course green leachate often mixes with surface water, thus more data may be warranted to determine the persistence and ecological significance of chronic exposure to these compounds of organisms in the aquatic environment. © 2001 Society of Chemical Industry
Achieving uniform noise in direct fan-beam CT reconstruction through bowtie filter design

This work concerns the standard deviation of computed tomography (CT) images reconstructed with the classical direct fan-beam FBP algorithm using noisy data taken over a full scan. We show how a suitable modification of the bowtie filter shape can yield reconstructions with relatively uniform noise profiles. These findings are supported with standard deviation profiles estimated with Monte Carlo Poisson noise simulations which incorporate the effects of the bowtie filter. In particular, we demonstrate that the standard deviation profile can be made nearly uniform by adding just one parameter to the description of the bowtie filter, and then optimizing this parameter. This result is shown to be robust to changes in the apodization of the ramp filter kernel as well as to changes in the noise level.
Flexible and transparent all-graphene circuits for quaternary digital modulations

In modern communication systems, modulation is a key function that embeds the baseband signal (information) into a carrier wave so that it can be successfully broadcasted through a medium such as air or cables. Here we report a flexible all-graphene modulator circuit with the capability of encoding a carrier signal with quaternary digital information. By exploiting the ambipolarity and the nonlinearity in a graphene transistor, we demonstrate two types of quaternary modulation schemes: quaternary amplitude-shift keying and quadrature phase-shift keying. Remarkably, both modulation schemes can be realized with just 1 and 2 all-graphene transistors, respectively, representing a drastic reduction in circuit complexity when compared with conventional modulators. In addition, the circuit is not only flexible but also highly transparent (~95% transmittance) owing to its all-graphene design with every component (channel, interconnects, load resistor and source/drain/gate electrodes) fabricated from graphene films. Signal modulation is a mechanism which embeds an information-carrying signal into a carrier wave to broadcast information and is essential for high-speed communication. Zhonget al. report a flexible, transparent all-graphene modulator circuit performing quaternary modulation schemes with only two transistors.
In Vitro Transcription and Immobilized Template Analysis of Preinitiation Complexes

In the study of gene regulation, it is often necessary to employ functional assays that investigate the action or mechanism of specific promoters or enhancer-binding factors and their role in transcription by RNA polymerase II. Although many assays measure the transcription of a gene under the control of an endogenous or model activator in vivo, it is often useful to recreate transcription in vitro in order to study specific regulatory mechanisms. In this unit, protocols are presented that will allow the investigator to perform in vitro transcription using preinitiation complexes assembled from cellular extracts on either naked DNA or chromatin templates.
Internationalization in Higher Education: Four Issues to Consider

I am very pleased to write this column for the Journal of College an Character, a journal that has had an influential history in addressing issues that many of us in student affairs have always been passionate about–holistic student development, integration of the mind and heart, self identity, engagement in the world, experiential learning, values, and spirituality. I now suggest that we include internationalization in our thinking and actions as educators. How do we guide and challenge students to live productively and meaningfully in a more pluralistic and diverse world? In my travels to many campuses over the past few years, I receive whole hearted agreement and strong commitment, especially from presidents and boards of trustees that we in U.S. universities must better prepare students to be global citizens. But what does this “preparation” mean and how can we create an environment on campus and beyond that effectively fosters holistic global learning and development?
Phosphodiesterase Type 5 Inhibitor Use and Hearing Impairment

Objective To compare use of phosphodiesterase type 5 inhibitors (PDE-5i) between participants with and without self-reported hearing impairment using logistic regression, with and without adjustment for potentially confounding sociodemographic, behavioral, and health-related characteristics. Design Cross-sectional. Setting United States. Patients A population-based sample of 11 525 men 40 years or older (248 217 013 weighted men) in the United States, selected from the Medical Expenditure Panel Survey (2003-2006). Main Outcome Measure Self-reported hearing impairment. Results The overall prevalence of self-reported hearing impairment and PDE-5i use in each group was 17.9% and 2%, respectively. Men who reported hearing impairment were more likely to have also reported the use of any PDE-5i (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.36-3.66). However, this association was limited to sildenafil (Viagra) (OR, 2.05; 95% CI, 1.23-3.43); no significant associations were observed for tadalafil (Cialis) or vardenafil (Levitra) (ORs, 1.40 [95% CI, 0.49-4.04] and 0.88 [95% CI, 0.35-2.22], respectively). Conclusions Current warnings regarding the risk of hearing loss related to PDE-5i use seems to be justified. However, the cross-sectional nature of the current study provides only limited insight regarding this relationship, and thus additional research is warranted.
Comparative Effectiveness of Three Prophylactic Strategies to Prevent Clinical Macular Edema after Phacoemulsification Surgery

Purpose To study the relationship of chemoprophylaxis and other factors with the occurrence of acute, clinical, postoperative macular edema. Design Retrospective cohort study. The drug regimens consisted of postoperative topical prednisolone acetate (PA) alone or with a nonsteroidal anti-inflammatory drug (NSAID) or intraoperative subconjunctival injection of 2 mg triamcinolone acetonide (TA) alone. Participants Patients undergoing phacoemulsification at Kaiser Permanente, Diablo Service Area, Northern California, from 2007 through 2013. Methods We identified incident macular edema diagnoses that had been recorded 5 to 120 days after phacoemulsification with visual acuity 20/40 or worse and evidence of macular thickening by optical coherence tomography. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from logistic regression analysis, conditioned on the surgeon and adjusted for year, patient age and race, diabetic retinopathy status, other ocular comorbidities, systemic comorbidities, and posterior capsular rupture status. Main Outcome Measures Incident rates of acute, clinical, postoperative macular edema. Results We confirmed 118 cases among 16 070 cataract surgeries (incidence, 0.73%). Compared with PA alone, the OR for the relationship of macular edema with PA+NSAID was 0.45 (95% CI, 0.21–0.95) and that for TA injection was 1.21 (95% CI, 0.48–3.06). The frequency of intraocular pressure spikes of 30 mmHg or more between postoperative days 16 and 45 was 0.6% in the topical PA group, 0.3% in the topical PA+NSAID group ( P = 0.13), and 0.8% for the TA group ( P = 0.52). Black race was associated with a risk of macular edema (OR, 2.86; 95% CI, 1.41–5.79). Conclusions Adding a prophylactic NSAID to PA treatment was associated with a reduced risk of macular edema with visual acuity of 20/40 or worse. The risk and safety of TA injection were similar to those of PA alone. Further research is needed on the prognostic significance of postoperative macular edema, the role of prophylaxis, the risk among black people, and the effectiveness of depot medications.
Origins of uncrossed retinofugal projections in normal and hypopigmented mice.

In albinos, the retinofugal projections to the ipsilateral side of the brain are reduced (e.g., see Guillery, 1969; La Vail et al., 1978; Lund, 1965). Although all ganglion cell types are affected, in mice the displaced ganglion cell population is the main target of the albino mutation (Drager & Olsen, 1980). Here we tested whether this preferential effect on displaced ganglion cells is a general consequence of the melanin reduction or a pleiotropic effect unique to the albino locus, by retrogradely tracing retinal ganglion cells in normal C57BL/6J mice and in several non-allelic hypopigmentation mutants on the same background: albino (C57BL/6J-c2J), beige (C57BL/6J-bg), pale ear (C57BL/6J-ep), ruby-eye/haze (C57BL/6J-ru-2hz), and pearl (C57BL/6J-pe). All mutants have lower overall cell counts in the ipsilateral projection, but the displaced population is disproportionately affected: the albinos contain 42% of the normal number of displaced ganglion cells, and the other mutants have an average 57% of normal counts. The reduction in uncrossed retinofugal projections in albinos affects the inputs to the lateral geniculate nucleus and the superior colliculus, but not to the suprachiasmatic nucleus (Drager, 1974). To address the question in which way the susceptible uncrossed projections differ from the nonsusceptible one, we compared ganglion cells backfilled from the suprachiasmatic nucleus to ganglion cells backfilled from the optic tract at geniculate level. Whereas the uncrossed optic tract projection originates from the binocular region in the ventro-temporal retina and contains a high fraction of large and displaced ganglion cells (Drager & Olsen, 1980), both the crossed and uncrossed inputs to the suprachiasmatic nucleus originate from the entire retina with a relative preference for the lower nasal region that corresponds to part of the monocular visual field; all ganglion cells projecting to the suprachiasmatic nucleus are of medium size, and they are located in the ganglion cell layer. These observations allow the following conclusions: (1) All genetic mutants which cause a reduction in ocular melanin, regardless of the molecular or cell-biological mechanism underlying the pigment reduction, result in decreased uncrossed projections; this confirms previous reports (La Vail et al., 1978, Sanderson et al., 1974). (2) The decrease affects only projections involved in binocular vision. (3) In mice, the ganglion cells displaced to the inner nuclear layer, and hence located closer to the retinal pigment epithelium, are disproportionately affected by the melanin reductions. These observations may provide cues to the spatio-temporal mechanism of the
Adaptive hierarchical modeling of heterogeneous structures

Abstract Predictability of the response of structural components to the action of external forces hinges on the selection of an appropriate mathematical and computational model of the governing physics. Invariably, this also involves decisions on what spatial and temporal scales are expected to be important in influencing the quality of the prediction. The process of model selection, particularly multiscale modeling, is not well defined and is often imprecise, heuristic, and the source of the most error in predicting physical behavior. This work presents a systematic technique for model selection and analysis of a class of multiscale problems encountered in the study of heterogeneous materials. The process, referred to as hierarchical modeling, consists of precisely characterizing a set of mathematical models of events of the smallest scale expected to influence the events of interest, and of developing rigorous a posteriori estimates of modeling error in the results obtained for one scale compared to models of finer scale. These estimated errors are then used in an adaptive process that automatically selects models and inherent spatial scales that produce simulations meeting preset error tolerances. The microstructures can be randomly distributed or deterministic or both, depending on the structure of models in the hierarchical set. The adaptive process can lead to models with non-uniform structure that depends upon boundary and initial data, loads and source terms, geometry, and other data. Several implementations of this process with applications to composite materials are described.
Preferences of Elderly Men for Prostate-Specific Antigen Screening and the Impact of Informed Consent

Background Use of the prostate-specific antigen (PSA) as a screening test remains highly controversial, particularly in older men. This study was undertaken to assess the impact of information on the preferences of older men for such screening. Methods The elderly cohort (age > or = 65 years) of a larger randomized trial was studied to determine the effect of a 3-minute scripted informational intervention on primary care patients' interest in PSA screening and on potential predictors of screening interest. Results Informed patients were significantly less interested in screening than were uninformed patients (p = .006). Informed patients considered PSA screening to be significantly less efficacious than did uninformed patients (p = .004), but among both uninformed and informed patients, perceived efficacy correlated with interest in screening (multivariate OR 2.3, 95% CI 1.5-3.8 for uninformed patients; OR 2.2, 95% CI 1.3-3.9 for informed patients). Perceived seriousness of prostate cancer predicted interest in screening among uninformed patients (OR 1.8, 95% CI 1.3-2.6), but not among informed patients. Informed patients who were married were less interested in screening than those who were single, divorced, or widowed (OR 0.3, 95% CI .08-0.9). Marital status did not predict screening interest among uninformed patients. Conclusions Involving elderly patients in the decision whether to screen with the PSA by providing them with information leads to a significant reduction in interest in such screening. Factors that appear to influence the screening preferences of informed elderly patients include perceived efficacy of screening and marital status, whereas uninformed patients are more likely to weigh the perceived seriousness of prostate cancer in their screening decision.
Beyond CMOS: Logic Suitability of InGaAs HEMTs

For over 30 years, Si CMOS scaling has brought along exponential improvements in chip density, speed and power consumption. With CMOS rapidly approaching fundamental limits, the "microelectronics revolution" is threatened. A way to reinvigorate logic technology is to introduce new channel materials with improved transport properties. In this, III-V compound semiconductors and, in particular, InGaAs with high InAs compositions are very promising. This paper reviews the merits and challenges of III-V's for logic applications. It also summarizes recent work of the authors in investigating the logic suitability of InGaAs HEMTs.
Encoding Natural Scenes with Neural Circuits with Random Thresholds

We present a general framework for the reconstruction of natural video scenes encoded with a population of spiking neural circuits with random thresholds. The natural scenes are modeled as space-time functions that belong to a space of trigonometric polynomials. The visual encoding system consists of a bank of filters, modeling the visual receptive fields, in cascade with a population of neural circuits, modeling encoding in the early visual system. The neuron models considered include integrate-and-fire neurons and ON-OFF neuron pairs with threshold-and-fire spiking mechanisms. All thresholds are assumed to be random. We demonstrate that neural spiking is akin to taking noisy measurements on the stimulus both for time-varying and space-time-varying stimuli. We formulate the reconstruction problem as the minimization of a suitable cost functional in a finite-dimensional vector space and provide an explicit algorithm for stimulus recovery. We also present a general solution using the theory of smoothing splines in Reproducing Kernel Hilbert Spaces. We provide examples of both synthetic video as well as for natural scenes and demonstrate that the quality of the reconstruction degrades gracefully as the threshold variability of the neurons increases.
Erratum: Calculating the peak skin dose resulting from fluoroscopically guided interventions. Part I: Methods

The squared term was missing from the factor in the original article. This term needs to be squared, as it applies to both the horizontal and vertical collimator dimensions. The correct form of the expression was used in the examples in the companion article: Calculating the peak skin dose resulting from fluoroscopically guided interventions. Part II: Case studies . (2) We wish to thank Guang Li, PhD, for bringing this omission to our attention. We would like to take this opportunity to make one additional clarification regarding these articles. The DICOM tag 0x00181111 (Distance Source to Patient) must be used carefully when calculating peak skin dose. The actual distance stored in this tag is affected by the choice of method used to calibrate distances in the image. In many cases, the distance stored in this tag is calculated based on the default table-to-object (TOD) distance used in the configuration files of the fluoroscope. However, the TOD setting can be changed by the operator or another method may be used to calibrate the images (e.g., catheter choice, an object such as a coin placed in the field of view, etc.). It is important that this be considered when using the distance stored in this tag.
Comparison of relative cerebral blood flow maps using pseudo‐continuous arterial spin labeling and single photon emission computed tomography

Pseudo-continuous arterial spin labeling (PCASL) MRI is a relatively new ASL technique and has the potential to extend the CBF measurement to all tissue types, including the white matter. However, arterial transit time (δa) for the white matter is not well established and a limited number of reports using multi-delay methods have yielded inconsistent findings. In the present study, we took a different approach and measured white matter δa, 1541±173 ms (mean±SD), by determining arrival times of exogenous contrast agent in a bolus tracking experiment. The data also confirmed δa of the gray matter as 912±209 ms. In the second part of this study, we used these parameters in PCASL kinetic models and compared relative CBF (rCBF, with respect to the whole brain) maps to those measured using a SPECT technique. It was found that the use of tissue-specific δa in the PCASL model was helpful in improving the correspondence between the two modalities. On a regional level, the gray/white matter CBF ratios were 2.47±0.39 and 2.44±0.18 for PCASL and SPECT, respectively. On a single voxel level, the variance between the modalities was still considerable, with an average rCBF difference of 0.27.
CNV-TV: A robust method to discover copy number variation from short sequencing reads

Copy number variation (CNV) is an important structural variation (SV) in human genome. Various studies have shown that CNVs are associated with complex diseases. Traditional CNV detection methods such as fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) suffer from low resolution. The next generation sequencing (NGS) technique promises a higher resolution detection of CNVs and several methods were recently proposed for realizing such a promise. However, the performances of these methods are not robust under some conditions, e.g., some of them may fail to detect CNVs of short sizes. There has been a strong demand for reliable detection of CNVs from high resolution NGS data. A novel and robust method to detect CNV from short sequencing reads is proposed in this study. The detection of CNV is modeled as a change-point detection from the read depth (RD) signal derived from the NGS, which is fitted with a total variation (TV) penalized least squares model. The performance (e.g., sensitivity and specificity) of the proposed approach are evaluated by comparison with several recently published methods on both simulated and real data from the 1000 Genomes Project. The experimental results showed that both the true positive rate and false positive rate of the proposed detection method do not change significantly for CNVs with different copy numbers and lengthes, when compared with several existing methods. Therefore, our proposed approach results in a more reliable detection of CNVs than the existing methods.
Under the umbrella: resisting the reign of rationalized educational reform

L'expression Whole Language est utilisee aux Etats-Unis pour designer l'enseignement et le developpement de l'alphabetisation. Elle implique des pratiques centrees sur l'enfant. A partir de l'interview de sept enseignants, l'A. presente leurs pratiques pedagogiques et leurs idees a propos du Whole Language
Neuroactive Insecticides: Targets, Selectivity, Resistance, and Secondary Effects

Neuroactive insecticides are the principal means of protecting crops, people, livestock, and pets from pest insect attack and disease transmission. Currently, the four major nerve targets are acetylcholinesterase for organophosphates and methylcarbamates, the nicotinic acetylcholine receptor for neonicotinoids, the γ-aminobutyric acid receptor/chloride channel for polychlorocyclohexanes and fiproles, and the voltage-gated sodium channel for pyrethroids and dichlorodiphenyltrichloroethane. Species selectivity and acquired resistance are attributable in part to structural differences in binding subsites, receptor subunit interfaces, or transmembrane regions. Additional targets are sites in the sodium channel (indoxacarb and metaflumizone), the glutamate-gated chloride channel (avermectins), the octopamine receptor (amitraz metabolite), and the calcium-activated calcium channel (diamides). Secondary toxic effects in mammals from off-target serine hydrolase inhibition include organophosphate-induced delayed n...
Self-presentation processes in job analysis: a field experiment investigating inflation in abilities, tasks, and competencies.

Although job analysis is a widely used organizational data collection technique, little research has investigated the extent to which job analysis information is affected by self-presentation processes. This study represents the first direct test of the propositions offered by F. P. Morgeson and M. A. Campion (1997) concerning self-presentation in job analysis measurement. Using an experimental design, the authors examined job incumbent response differences across ability, task, and competency statements. Results indicated that ability statements were more subject to inflation than were task statements across all rating scales. Greater endorsement of nonessential ability statements was responsible for the differences. This produced higher endorsement of ability items but lower mean ratings. Finally, frequency and importance ratings of global competency statements were generally higher than decomposed ability and task scales, but required-at-entry judgments demonstrated the opposite relationship. Job analysis data is perhaps the most widely gathered type of organizational information for developing human resource (HR) management systems. It forms the foundation upon which many important HR management systems are built (Butler & Harvey, 1988), including selection systems, training programs, performance management programs, and compensation systems. The seemingly straightforward character of collecting information about jobs has led many to assume that job analysis methods result in reliable, valid, and unbiased information. It has recently been suggested, however, that job analysis information may be subject to numerous social and cognitive sources of inaccuracy (Morgeson & Campion, 1997). Such inaccuracies can negatively affect the HR systems that rely on job analysis. This study examined how selfpresentation processes can serve to inflate job analysis responding and represents the first direct test of the propositions outlined by
Sleep electroencephalographic response to muscarinic and serotonin1A receptor probes in patients with major depression and in normal controls

Abstract Background: To test the hypothesis that depression is associated with an increased ratio of cholinergic to serotonergic neurotransmission, we compared the effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5-HT) 1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy subjects. We hypothesized, adopting the reciprocal interaction model, that the effects on REM sleep of these probes within the same individuals are negatively correlated and unmask neurobiological changes in depression. Methods: Polysomnographic recordings were obtained in 12 unmedicated patients with a current major depression and 12 normal controls. They received placebo, pilocarpine 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after premedication with the peripheral anticholinergic probanthine 30 mg, double blind, counterbalanced) on three occasions. Results: Pilocarpine shortened and ipsapirone prolonged REM latency equally in both groups. These effects were not correlated. Pilocarpine decreased slow-wave sleep and EEG delta power during the first nonREM episode more in controls than in patients, and enhanced EEG sigma power equally in both groups. Ipsapirone had no significant effects on EEG power. Conclusion: These data do not support the postulate of muscarinic receptor up-regulation and 5-HT 1A receptor down-regulation in depression. The significance of blunted delta power suppression in patients following pilocarpine warrants further investigations.
Transient gain dynamics in wide bandwidth discrete Raman amplifiers

This paper has described measurements of transient gain effects caused by dropping channels in a wide bandwidth backward pumped discrete Raman amplifier. These measurements have shown that in a WDM amplifier the transients include two different features. There is a small but fast component due to signal-to-signal Raman crosstalk which can either increase or decrease the signal power depending on whether the surviving channels are at a longer or shorter wavelength than the dropped channels. There is also a larger, slower component due to pump readjustment which occurs on a time scale determined by the length of the amplifier. After changing the signal power at the input to the amplifier it requires up to three times the transit time of the amplifier for the new steady state to be reached.