cssi/SciSciGPT-SciSciNet huggingface dataset:
Recent trends in stock-recruitment of Blackwater herring (Clupea harengus L.) in relation to larval production

Recruitment at age 2 plotted against spawning stock biomass (SSB) for the Blackwater herring stock shows a dome-shaped pattern. This has been apparent in recent years (1991–1995) when, despite high spawning stock biomass, resulting year classes have been poor. In 1994, 1996 and 1997 plankton surveys were undertaken in the Blackwater Estuary to estimate the production of yolk-sac larvae. The results of production, average cohort growth and mortality were compared with the results from surveys carried out in 1979 when spawning stock biomass (SSB) was close to the minimum historically recorded. In each year of the present study, estimated levels of larval production were higher than in 1979. Following hatching, average cohort growth rates appeared to be similar to those in 1979 but mortality rates appeared to be greater. Levels of larval production increased linearly with spawning stock biomass but there was an inverse relationship between estimated survival from hatching to recruitment at age 2 and the level of larval production. The results suggest that, in the years studied, year-class strength was determined by density dependent and/or environmental processes operating after hatching as opposed to processes operating at the egg stage.
An autoradiographic study of long-term follicular development in the cyclic hamster

The time required for ovarian follicular development in the cyclic hamster was determined by marking follicles with [3H]-thymidine on day 1 of the estrous cycle (day of ovulation) and by following their fate over the next three cycles by autoradiography. A model of follicular development was formulated, based on the total number of follicles and the changing percentage of labelled follicles with time. It was estimated that 20 days elapsed before a preantral follicle with two to three layers of granulosa cells (stage 1) was able to ovulate. Follicles spent eight days in stage 1 and an additional eight days in stage 2 (4-5 granulosa layers). Preantral follicles entering stage 3 (6-7 granulosa layers) and 4 ( 8 layers) on day 1 of the cycle ovulated four days later. Approximately 30 follicles per ovary entered and left stage 1 each cycle, representing a 50% turnover. Of the follicles leaving stage 1, about 50% were transformed into stage 2 follicles; the remaining ones underwent atresia. Stage 2 follicles also had a 50% turnover each cycle. Half of the stage 2 follicles underwent atresia; the remainder developed into stages 3 and 4 follicles Fifty percent of the stages 3 and 4 follicles present on day 1 of the cycle ovulated at the next estrus with the remainder undergoing atresia.
Analysis of coregistered Landsat, Seasat and SIR‐A images of varied terrain types

Multisensor image data (SIR-A, Seasat SAR and Landsat MSS) over areas in nothern Algeria and eastern Utah have been coregistered in order to assess the complementary effects of the orbital sensors for geologic mapping in two very different terrains. This first attempt at registering such a data set shows that the radar backscatter information provided by the SIR-A image increases the classification accuracy of several geologic units over the Landsat image alone, and over combined Landsat and Seasat images.
Pilot Study on the Effect of Ramelteon on Sleep Disturbance After Traumatic Brain Injury: Preliminary Evidence From a Clinical Trial

Abstract Objective To investigate the effect of ramelteon on sleep and daytime functioning among individuals with traumatic brain injury (TBI). Design A double-blind, placebo-controlled study with a crossover design. Setting A research facility attached to an acute rehabilitation hospital. Participants Individuals with TBI (N=13) complaining of sleep difficulties with a Pittsburgh Sleep Quality Index score >5. Interventions A nightly dosage of ramelteon (8mg) was given over a period of 3 weeks. Main Outcome Measures An actigraph and a daily sleep log were used to measure sleep/wake patterns. Daytime functioning was measured after 3 weeks of treatment using a computer-administrated neuropsychological test battery in conjunction with subjective questionnaires measuring mood, daytime sleepiness, and fatigue. Results A significant increase in objectively measured total sleep time and a small increase in sleep latency were observed after 3 weeks of treatment compared with placebo. Treatment also showed a significant increase in standardized neuropsychological test scores, with a particular improvement on an index of executive functioning. Conclusions Preliminary evidence for the effectiveness of 8mg of ramelteon taken nightly over a 3-week period was found in the treatment of sleep difficulties among individuals with TBI. Improvements in total sleep time and some aspects of cognitive functioning are discussed.
Cross-Species RNAi Rescue Platform in Drosophila melanogaster

RNAi-mediated gene knockdown in Drosophila melanogaster is a powerful method to analyze loss-of-function phenotypes both in cell culture and in vivo. However, it has also become clear that false positives caused by off-target effects are prevalent, requiring careful validation of RNAi-induced phenotypes. The most rigorous proof that an RNAi-induced phenotype is due to loss of its intended target is to rescue the phenotype by a transgene impervious to RNAi. For large-scale validations in the mouse and Caenorhabditis elegans, this has been accomplished by using bacterial artificial chromosomes (BACs) of related species. However, in Drosophila, this approach is not feasible because transformation of large BACs is inefficient. We have therefore developed a general RNAi rescue approach for Drosophila that employs Cre/loxP-mediated recombination to rapidly retrofit existing fosmid clones into rescue constructs. Retrofitted fosmid clones carry a selection marker and a phiC31 attB site, which facilitates the production of transgenic animals. Here, we describe our approach and demonstrate proof-of-principle experiments showing that D. pseudoobscura fosmids can successfully rescue RNAi-induced phenotypes in D. melanogaster, both in cell culture and in vivo. Altogether, the tools and method that we have developed provide a gold standard for validation of Drosophila RNAi experiments.
Surface Fluxes and Ocean Coupling in the Tropical Intraseasonal Oscillation

Sensitivity of tropical intraseasonal variability to mixed layer depth is examined in the modified National Center for Atmospheric Research Community Atmosphere Model 2.0.1 (CAM), with relaxed Arakawa‐Schubert convection, coupled to a slab ocean model (SOM) whose mixed layer depth is fixed and geographically uniform, but varies from one experiment to the next. Intraseasonal west Pacific precipitation variations during boreal winter are enhanced relative to a fixed-SST (infinite mixed layer depth) simulation for mixed layer depths from 5 to 50 m, with a maximum at 20 m [interestingly, near the observed value in the regions where the Madden‐ Julian oscillation (MJO) is active], but are strongly diminished in the 2-m depth simulation. This nonmonotonicity of intraseasonal precipitation variance with respect to mixed layer depth was predicted by Sobel and Gildor using a highly idealized model. Further experiments with the same idealized model help to interpret results derived from the modified NCAR CAM. A sensitivity study shows that the convection‐surface flux feedback [wind-induced surface heat exchange (WISHE)] is important to the intraseasonal variability in the CAM. This helps to explain the behavior of the 2-m SOM simulation and the agreement with the idealized model. Although intraseasonal SST variations are stronger in the 2-m SOM simulation than in any of the other simulations, these SST variations are phased in such a way as to diminish the amplitude of equatorial latent heat flux variations. Reducing the mixed layer depth is thus nearly equivalent to eliminating WISHE, which in this model reduces intraseasonal variability. The WISHE mechanism in the model is nonlinear and occurs in a region of mean low-level westerlies. Since a very shallow mixed layer is effectively similar to wet land, it is suggested that the mechanism described here may explain the local minimum in MJO amplitude observed over the Maritime Continent region.
Malaria in Sucre State, Venezuela

The author reviews the malaria research program in Sucre State, Venezuela, taking an ecosystem approach. The goal was to determine which methods could have been introduced at the onset that would have made the study more ecological and interdisciplinary. Neither an ecosystem approach nor integrated disease control were in place at the time of the study. This study began to introduce an ecosystem approach when two contrasting ecosystems in Sucre State were selected for study and vector control methods were implemented based on research results. The need to have a health policy in place with an eco-health approach is crucial to the success of research and control. The review suggests that sustainability is low when not all the stakeholders are involved in the design and implementation of the research and control strategy development. The lack of community involvement makes sustainability doubtful. The author concludes that there were two interdependent challenges for malaria control: development of an ecosystem approach for malaria research and control, and the implementation of an integrated disease control strategy, with malaria as one of the important health issues.
Teachers Attitudes Toward Increased Mainstreaming: Implementing Effective Instruction for Students with Learning Disabilities

To investigate the types of instructional strategies offered in mainstream classes, we asked 127 mainstream teachers in Grades 1 through 8 to complete a self-evaluation concerning instructional strategies used in their general education classes. Also, each teacher completed questionnaires concerning their attitudes toward their own efficacy and toward mainstreaming. ANOVAs comparing teachers with positive attitudes toward mainstreaming and teachers with less positive attitudes indicated that the teachers with less positive attitudes used effective mainstream instructional strategies less frequently. Implications of these results in terms of recent educational initiatives resulting in increased inclusion programs are discussed.
Schematic specification of datapath layout

A graphical assembly language for specifying custom VLSI datapaths is described. By applying certain restrictions to the format, hierarchical annotated schematics which specify the logical structure of a datapath can also be used to specify the physical layout. The close coupling of the logical and physical specifications allows more efficient implementations by highlighting the implications of architectural decisions for the layout. The format restrictions make it possible for the schematics to exactly specify the datapath physical interface on the top and the bottom of the layout, thereby enabling datapaths to be stacked with other separately assembled datapaths and submodules. This approach represents a good compromise between very high level compiled design and direct layout specification, and has been used successfully in six designs. >
Treatment of eczema herpeticum with systemic acyclovir.

Eczema herpeticum, a form of disseminated cutaneous herpes simplex infection, is a potentially life-threatening illness. 1 Herpes simplex virus may disseminate either cutaneously or systemically in patients with preexisting cutaneous disease, including Darier's disease, pemphigus vulgaris, ichthyosis vulgaris, mycosis fungoides, and most commonly, atopic dermatitis. 1,2 The initial manifest herpes simplex virus infection may be from a primary exposure or after reactivation of a latent infection. The latter infection, occurring in patients with certain preexisting dermatoses, may manifest initially with a localized cluster of lesions which, with time, may disseminate over a larger skin surface area. The manifestation may be confused with an exacerbation of the underlying skin disease until the characteristic vesicles are noted. When associated with atopic dermatitis, the most intense viral dissemination is located in the areas of dermatitis, but normal appearing skin may ultimately be involved. Crops of new vesicles continue to erupt for two to
Prevention of Coronary Heart Disease and the National Cholesterol Education Program

The incubation period for the progression of atherosclerosis to clinical disease is long, which provides an opportunity for risk factor modification and prevention of coronary heart disease (CHD). The National Cholesterol Education Program (NCEP) utilized the Framingham risk score (FRS) to classify individuals by level of risk to receive drug therapy and/or dietary counseling to lower low-density lipoprotein cholesterol (LDL-C) and raise high-density lipoprotein cholesterol (HDL-C). The rationale for choosing specific cutpoints for treatment was based on 3 key variables: (1) the efficacy of drug therapy to reduce the CHD incidence, (2) the safety of drug therapy, and (3) the cost of therapy. Article p 647 The Multi-Ethnic Study of Atherosclerosis (MESA)1 has reinforced previous observations that the guidelines are not being fully implemented. Many individuals are not treated or are undertreated. In MESA, only 54% were undergoing drug therapy, and only 40% of the dyslipidemic individuals had their blood cholesterol levels under control. This is overestimated, because individuals currently being treated with lipid-lowering drugs were dyslipidemic by NCEP criteria. Likely, many of these individuals were placed on therapy by doctors even if they did not meet the NCEP criteria. Not surprisingly, guidelines are being followed less for poorer individuals and minorities. A recent detailed report in Circulation discussed the reason for failure to follow guidelines and reduce lipid levels.2 Almost all of the successful studies of diet or drug effectiveness have included the addition of nurses, nutritionists, health advisors, and good follow-up in addition to traditional physician-patient interactions. Unfortunately, most insurance, including Medicare, does not pay for these “services” to maximize adherence.3,4 MESA has provided the first good approach for determining whether the FRS or the NCEP guidelines are related to the extent of coronary atherosclerosis, as measured by coronary calcification. This evaluation has put in …
Topology of prostaglandin H synthase-1 in the endoplasmic reticulum membrane

Prostaglandin H synthase-1 is an integral endoplasmic reticulum membrane protein which catalyzes a key control step in prostaglandin biosynthesis. The overall arrangement of the prostaglandin H synthase-1 polypeptide with respect to the endoplasmic reticulum membrane was examined in transiently transfected COS-1 cells, using immunofluorescence microscopy. A bacterial toxin, streptolysin-O, was used for selective plasma membrane permeabilization and a detergent, saponin, for general membrane permeabilization. Treated cells were probed with six antibodies specific for particular prostaglandin H synthase-1 peptide segments and one antibody specific for an inserted viral reporter epitope. Control experiments established that actin, a cytoplasmic marker, was accessible to fluorescein-labeled phalloidin after streptolysin-O treatment, whereas antibodies against protein disulfide isomerase, an endoplasmic reticulum lumenal marker, bound only after saponin treatment, Using this approach to investigate prostaglandin H synthase-1, it was found that streptolysin-O treatment was sufficient to obtain staining of intracellular membranes by antibodies specific for the endogenous C-terminal segment, for the viral reporter inserted at the C-terminus, and for the protease-sensitive region near arg277. In contrast, saponin treatment was necessary for staining by antibodies specific for peptides spanning residues 51-66, 156-170, and 377-390. Antibodies targeted against residues 483-496 did not stain transfected cells even after saponin permeabilization, although they did bind to detergent-solubilized prostaglandin H synthase-1. These results indicate that the C-terminus and arg277 regions of the synthase can be exposed on the cytoplasmic side of the endoplasmic reticulum membrane, whereas regions near N-glycosylation sites are confined to the endoplasmic reticulum lumen and residues 483-496 are inaccessible from either side of the endoplasmic reticulum membrane.
Efficiency measurement in stochastic input-output systems†

Measuring efficiency of systems with multiple inputs and multiple outputs is most difficult when market, prices for these inputs and outputs are unavailable as for example in most public sector decision-making units. Two types of measures related to Pareto-efficiency could still be defined in such a framework, one related to the productivity of a common set of inputs and the other to a ratio of weighted index of outputs and inputs. These measures however are ordinal and useful in ranking purposes only and may have stochastic variations when the multivariate input-output system contains random components. Some characterizations and theoretical results are derived here for some specific types of random variations. Potential applications are also briefly indicated.
Aflatoxin accumulation and kernel infection of maize hybrids inoculated with Aspergillus flavus and Aspergillus parasiticus

Over a three year period, we compared aflatoxin accumulation and kernel infection in maize hybrids inoculated with Aspergillus flavus isolate NRRL 3357, A. flavus isolate NRRL 19772, Aspergillus parasiticus isolate NRRL 6111, and all combinations of these isolates. Maize hybrids were inoculated with the Aspergillus strains using the side-needle technique at 7 days after midsilk (50% of the plants had silks emerged). Aspergillus kernel infection and aflatoxin contamination were determined at ca. 63 days after midsilk. A. flavus isolate 3357 induced high levels of aflatoxin contamination in the maize grain which was similar to levels found when this isolate was combined with the other two Aspergillus isolates. Kernel infection levels were higher in one hybrid when a combination of isolates including isolate 3357 was used. A. flavus isolate 3357 has been used to evaluate maize germplasm for aflatoxin resistance in the south-eastern USA for over 30 years. Our studies determined that inoculating plants with A....
Pore Scale Simulation of Combustion in Porous Media

This paper describes an improved methodology for studying combustion in porous media in pore scale. Porous media combustion is one technology having advantages over the conventional combustion system. Examples of combustion in porous media are presented to show the potential application of the present mesh-based microstructure representation algorithm (MBMRA).
Racial disparities in emergency general surgery: Do differences in outcomes persist among universally insured military patients?

BACKGROUNDRacial disparities in surgical care are well described. As many minority patients are also uninsured, increasing access to care is thought to be a viable solution to mitigate inequities. The objectives of this study were to determine whether racial disparities in 30-/90-/180- day outcomes
Two New Members of the Mucorales

A new genus is based on a Mucor-like species that produces conidia, sporangioles, and columellate, multispored sporangia. The new genus belongs in the Mucoraceae but morphologically it shows some r...
Realization and Application of Open Experimental Platform Based on Linux

The major work of this paper is the research of experimental teaching in university and Laboratory usage.In order to solve the problems of low utilization of laboratory and few experiments based on Unix/Linux,we try to set up open experimental platform for multi-course based on Linux operation system.This program has been proved to be effective and productive and the most important is to provide beneficial idea to operation system experiment teaching reform.
Study on Behavior of Immerged Side-blowing Gas Jet into Molten Metal Bath

The behavior of immerged side-blowing gas jet into liquids and the mixing rate in the bath have been investigated by a water modeling and CFD simulation,based on a discussion of results obtained by J.Themelis,J.Szekely and G.N.Oryall,and J.K.Brimacombe on the same topic.It has been found that the trajectory of side-blowing gas jet in liquids is significantly influenced by bubble formation.The calculation method of side-blowing gas jet trajectory proposed by J.Themelis and J.Szekely can not give a reasonable presentation of actual phenomena.
Relationships among different subjective measurements of consumer health information retrieval performance.

Abstract Background: Millions of consumers perform health informationretrieval (HIR) online. To better understand the consumers’ per-spective on HIR performance, we conducted an observation andinterview study of 97 health information consumers. Methods: Consumers were asked to perform HIR tasks and werecorded their view regarding pe rformance using several differ-ent subjective measurements: finding the desired information,usefulness of the information found, satisfaction with the infor-mation, and intention to continue searching. Statistical analysiswas applied to verify if the multiple subjective measurementswere redundant.Result: The measurements ranged from slight agreement to noagreement among them. A number of reasons were identified forthis lack of agreement. Conclusion: Although related, the four subjective measurementsof HIR performance are distinct from each other and carried dif-ferent useful information. Keywords: Consumer Informatics, Information retrieval, Evaluation Introduction
An Epidemiological Perspective on College Student Health and Sleep

It is estimated that some 40% of all young adults aged 18 to 25 years are enrolled in either a twoor four-year college [1]. A figure of approximately twelve million young adults, as college students, attend predominantly 4-year colleges with a recent surge in the overall total number of students coming from a peak in 2-year college enrollments [1]. Estimates of 50% of all 18-25 year olds are labor market participants [1] and an additional some 500,000 students were attending nondegree institutions of higher education.
Viewpoint: Why APhA Should Reject Its Code of Ethics

The American Pharmaceutical Association is in the process of revi ing its Code of Ethics, first established in 1852 and revisedfour times since, most recently in 1981. The author is one qf eight people on the committee to revise the Code; it is expected to take several years.
Individual variation in size of the human red and green visual pigment gene array.

Purpose. To determime the size variation of the X-chromosomal human red and green visual pigment gene array in the general population using pulsed field get electrophoresis and Southern blotting. Methods. Peripheral blood lymphocytes were prepared from 67 anonymous males. The cells were embedded in agarose and the genomic DNA digested with restriction enzyme Not I. The resulting DNA fragments were resolved on a contour-clamped homogeneous electric field gel, and the Not I fragment containing the red and green pigment genes was visualized by Southern blot hybridization with a human green pigment cDNA probe. Results. In DNA from each male, a single hybridizing fragment was observed in Not I-digested DNA. The lengths of the fragments from different males were observed to vary in steps of approximately 39 kilobases (kb), consistent with earlier studies showing a visual pigment gene repeat unit of 39 kb and a head-to-tail tandem arrangement of the red and green visual pigment genes. In the population studied, the number of repeat units per X-chromosome had a mean of 2.9 and a standard deviation of 0.94. Conclusions. The sizes of visual pigment gene arrays observed in this study resemble those determined in earlier studies based on ratios of restriction fragments resolved by conventional get electrophoresis and visualized by whole genome Southern blotting, but differ significantly from those determined using ratios of fragments obtained by the polymerase chain reaction.
Evaluation of individual and area-level factors as modifiers of the association between warm-season temperature and pediatric asthma morbidity in Atlanta, GA.

Abstract Introduction Previous studies have found associations between respiratory morbidity and high temperatures; however, few studies have explored associations in potentially sensitive sub-populations. Methods We evaluated individual and area-level factors as modifiers of the association between warm-season (May-Sept.) temperature and pediatric respiratory morbidity in Atlanta. Emergency department (ED) visit data were obtained for children, 5–18 years old, with primary diagnoses of asthma or respiratory disease (diagnoses of upper respiratory infections, bronchiolitis, pneumonia, chronic obstructive pulmonary disease, asthma, or wheeze) in 20-county Atlanta during 1993–2012. Daily maximum temperature (Tmax) was acquired from the automated surface observing station at Atlanta Hartsfield International Airport. Poisson generalized linear models were used to estimate rate ratios (RR) between daily Tmax and asthma or respiratory disease ED visits, controlling for time and meteorology. Tmax effects were estimated for single-day lags of 0–6 days, for 3-, 5-, and 7-day moving averages and modeled with cubic terms to allow for non-linear relationships. Effect modification by individual factors (sex, race, insurance status) and area-level socioeconomic status (SES; ZIP code levels of poverty, education, and the neighborhood deprivation index) was examined via stratification. Results Estimated RRs for Tmax and pediatric asthma ED visits were positive and significant for lag days 1–5, with the strongest single day association observed on lag day 2 (RR=1.06, 95% CI: 1.03, 1.09) for a change in Tmax from 27 °C to 32 °C (25th to 75th percentile). For the moving average exposure periods, associations increased as moving average periods increased. We observed stronger RRs between Tmax and asthma among males compared to females, non-white children compared to white children, children with private insurance compared to children with Medicaid, and among children living in high compared to low SES areas. Associations between Tmax and respiratory disease ED visits were weak and non-significant (p-value>0.05). Conclusions Results suggest socio-demographic factors (race/ethnicity, insurance status, and area-level SES) may confer vulnerability to temperature-related pediatric asthma morbidity. Our findings of weaker associations among children with Medicaid compared to other health insurance types and among children living in low compared to high SES areas run counter to our belief that children from disadvantaged households or ZIP codes would be more vulnerable to the respiratory effects of temperature. The potential reasons for these unexpected results are explored in the discussion.
3q26.2/EVI1 rearrangement is associated with poor prognosis in classical Philadelphia chromosome-negative myeloproliferative neoplasms

Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown. Here we reported 15 patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms showing 3q26.2 rearrangement, including inv(3)(q21q26.2) (n=6), t(3;21)(q26.2;q22)(n=4), t(3;3)(q21;q26.2)(n=3), inv(3)(q13.3q26.2)(n=1), and t(3;12)(q26.2;p13)(n=1). In addition to 3q26.2 rearrangement, 9 of 15 cases had other concurrent karyotypical abnormalities, including -7/7q- and -5/5q-. There were 8 men and 7 women with a median age of 59 years (range, 35-79 years) at initial diagnosis of myeloproliferative neoplasms: 8 patients had primary myelofibrosis, 4 had polycythemia vera, and 3 had essential thrombocythemia. JAK2 V617F mutation was detected in 8/14 patients, including 4/4 with polycythemia vera. The median interval from the initial diagnosis of myeloproliferative neoplasms to the detection of 3q26.2 rearrangement was 44 months (range, 1-219 months). At time of emergence of 3q26.2 rearrangement, 11 patients were in blast phase and 2 patients had increased blasts (6-19%). Dyspoiesis, predominantly in megakaryocytes, were detected in all patients with adequate specimens at time of 3q26.2 rearrangement. Following 3q26.2 rearrangement, 12 patients received chemotherapy, but none of them achieved complete remission. Of 14 patients with follow-up information, all died with a median overall survival time of only 3 months (range 0-14 months) after the emergence of 3q26.2 rearrangement. In summary, 3q26.2 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is associated with other concurrent cytogenetic abnormalities, a rapid disease progression and blast transformation, a poor response to chemotherapy and a dismal prognosis.
Autonomous Robot Navigation Using Traversability Indices

Abstract The concepts of Local, Regional, and Global Traversability Indices have been introduced recently (Seraji, 1999, 2000, 2001). These indices represent the suitability of a terrain for traversal by a mobile robot at different scales of resolution. This paper utilizes these indices to develop a navigation strategy for a mobile robot traversing a challenging terrain. The traversability indices form the basis of three navigational behaviors; namely, Traverse-Local, Traverse-Regional, and Traverse-Global behaviors. These behaviors are blended with the Seek-Goal behavior to ensure that the mobile robot reaches the goal safely while avoiding obstacles and impassable terrain segments. The paper is concluded by an illustrative graphical simulation study.
Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay

Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors. We report here the development of a high affinity (KD = 200 nM) inhibitor from a low affinity fragment hit with supporting biochemical and structural data showing these molecules bind to the cGAS active site. We also report a new high throughput cGAS fluorescence polarization (FP)-based assay to enable the rapid identification and optimization of cGAS inhibitors. This FP assay uses Cy5-labelled cGAMP in combination with a novel high affinity monoclonal antibody that specifically recognizes cGAMP with no cross reactivity to cAMP, cGMP, ATP, or GTP. Given its role in the innate immune response, cGAS is a promising therapeutic target for autoinflammatory disease. Our results demonstrate its druggability, provide a high affinity tool compound, and establish a high throughput assay for the identification of next generation cGAS inhibitors.
Three Problems in Locke’s Ontology of Substance and Mode

Locke holds that we have two radically different types of ideas. Ideas of substances like a horse, a pig, and the metal gold are designed to correspond to things in the world that exist and have their properties independently of our ideas. Mode ideas have the opposite direction of fit. They are not meant to capture independently existing archetypes but rather function as categories that we impose on the world. Examples of mode ideas are the idea of a rainbow, a tune, a duel, and etching. But this category is important for Locke because it includes the key ideas of mathematics and morality. Thus, Locke’s distinction between two types of ideas corresponds to a distinction between bodies of knowledge that derive norms from observation (the various sorts of natural philosophy) and those intended to prescribe norms (mathematics and ethics). But although this way of thinking is fundamental to Locke’s moral epistemology, I argue that he has some difficulty accommodating the substance-mode ontology with his other metaphysical and semantic commitments.
The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer

Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations. Here, we tested the effects of NRF2 modulation (activation by sulforaphane or inhibition by brusatol) in lung carcinogenesis using a chemical (vinyl carbamate) model in A/J mice and a genetic (conditional KrasG12D oncogene expression, to simulate spontaneous oncogene mutation) model in C57BL/6J mice. Mice were treated with NRF2 modulators before carcinogen exposure or KrasG12D expression to test the role of NRF2 in cancer initiation, or treated after tumor development to test the role of NRF2 in cancer progression. Lung tissues were analyzed to determine tumor burden, as well as status of NRF2 and KRAS pathways. Additionally, proliferation, apoptosis, and oxidative DNA damage were assessed. Overall, NRF2 activation prevents initiation of chemically induced cancer, but promotes progression of pre-existing tumors regardless of chemical or genetic etiology. Once tumors are initiated, NRF2 inhibition is effective against the progression of chemically and spontaneously induced tumors. These results have important implications for NRF2-targeted cancer prevention and intervention strategies.
Case series: Monoarticular rheumatoid arthritis.

Objective Monoarticular presentation of rheumatoid arthritis is infrequent and has been previously reported to involve large joints such as the hip and knee joints. Here we report a case series of four patients presenting to the University of Michigan in 2015 with monoarticular rheumatoid arthritis, one with small and three with large joint involvement. Material and methods In total, four patients with monoarticular rheumatoid arthritis were treated in the Division of Rheumatology, University of Michigan. All the patients were retrospectively reviewed with permission from our Institutional Review Board; informed consent was provided by the patients for enrollment in a clinical trial for patients with rheumatoid arthritis. All the patients were assessed using the 2010 ACR/EULAR classification criteria for rheumatoid arthritis. Results All the patients presented with monoarthritis; three patients had large joint involvement and one had small joint involvement. Serologies were positive, with each patient having positive Anti-cyclic citrullinated peptide (anti-CCP) antibodies, two patients having a positive rheumatoid factor, three patients having elevated CRP levels, and one patient having positive ESR. All patients met the criteria of the duration of symptoms being at least 6 weeks. The findings of imaging, although not a part of the criteria, were consistent with active rheumatoid arthritis in all the patients. Conclusion While the 2010 ACR/EULAR classification criteria are the most sensitive criteria for diagnosing RA to date, the exclusion of these cases of monoarthritis demonstrates that further specificity can still be achieved for diagnosing these types of patients as early as possible using the current guidelines. Further, we suggest the inclusion of an imaging measure added to the inclusion criteria to further increase the yield in establishing diagnosis of rheumatoid arthritis in the current reported patient population.
Dancing Backwards in High Heels: Female Professors Experience More Work Demands and Special Favor Requests, Particularly from Academically Entitled Students

Although the number of U.S. female professors has risen steadily in recent years, female professors are still subject to different student expectations and treatment. Students continue to perceive and expect female professors to be more nurturing than male professors are. We examined whether students may consequently request more special favors from female professors. In a survey of professors (n = 88) across the United States, Study 1 found that female (versus male) professors reported getting more requests for standard work demands, special favors, and friendship behaviors, with the latter two mediating the professor gender effect on professors’ self-reported emotional labor. Study 2 utilized an experimental design using a fictitious female or male professor, with college student participants (n = 121) responding to a scenario in which a special favor request might be made of the professor. The results indicated that academically entitled students (i.e., those who feel deserving of success in college regardless of effort/performance) had stronger expectations that a female (versus male) professor would grant their special favor requests. Those expectations consequently increased students’ likelihood of making the requests and of exhibiting negative emotional and behavioral reactions to having those requests denied. This work highlights the extra burdens felt by female professors. We discuss possible moderators of these effects as well as the importance of developing strategies for preventing them.
Cardiovascular Response to Mental Stress in Mild Cognitive Impairment and its Association with Cerebral Perfusion

Mental stress has been linked to various chronic diseases including Alzheimer's disease, but the mechanisms underlying cognitive decline with mental stress are unknown. Reduced cardiovascular response to stress is associated with cardiovascular disease, and the latter is associated with cognitive impairment. We measured electrodermal activity, blood pressure, and cardiac hemodynamics in cognitively normal and mild cognitive impairment (MCI) adults (n = 76, mean age = 58 years, 46% MCI) during rest, a math test, and face-name recall tasks to derive the following cardiovascular indicators: mean arterial pressure, heart rate, stroke volume and cardiac output. These indicators were compared between the two groups. Cerebral blood perfusion via arterial spin-labeling MRI was measured in a subgroup who underwent an MRI scan (n = 30). Following exposure to mental stress, a decrease in stroke volume (p = 0.024) and cardiac output (p = 0.005) was found in the MCI group, but an increase in both parameters in the cognitively normal group. This difference was largest during face-name recall (standardized difference in stroke volume = -0.50, p = 0.029, and in cardiac output = -0.52, p = 0.023). Cardiac output during mental stress, but not at rest, decreased with cerebral perfusion (normal: p = 0.078, β= 1.97, R2 = 0.090; MCI: p = 0.007, β= 2.02, R2 = 0.008). No significant difference was found between the two groups at rest. This preliminary study suggests that individuals with MCI have an insufficient cardiac output, and in turn lower cerebral perfusion in response to mental stress.
Segmenting and Targeting Your Market: Strategies and Limitations

Excerpt] Almost any marketing textbook will tell you that the key to successful marketing can be summed up by the STP strategy—that is, segmentation, targeting, and positioning. This approach suggests that the mass market consists of some number of relatively homogeneous groups, each with distinct needs and desires. STP marketers attempt to identify those market segments, direct marketing activities at the segments which the marketers believe that their company can satisfy better than their competitors, and position their product offering so as to appeal to the targeted segments. Undoubtedly, your hospitality firm uses some form of this approach.
Multimedia Storage Systems

Multimedia storage servers provide access to multimedia objects including text, images, audio, and video. Due to the real-time storage and retrieval requirements and the large storage space and data transfer rate requirements of digital multimedia, however, the design of such servers fundamentally differs from conventional storage servers. Architectures and algorithms required for designing digital multimedia storage servers is the subject matter of this chapter.
Bridging immunogenetics and immunoproteomics: Model positional scanning library analysis for Major Histocompatibility Complex class II DQ in Tursiops truncatus

The Major Histocompatibility Complex (MHC) is a critical element in mounting an effective immune response in vertebrates against invading pathogens. Studies of MHC in wildlife populations have typically focused on assessing diversity within the peptide binding regions (PBR) of the MHC class II (MHC II) family, especially the DQ receptor genes. Such metrics of diversity, however, are of limited use to health risk assessment since functional analyses (where changes in the PBR are correlated to recognition/pathologies of known pathogen proteins), are difficult to conduct in wildlife species. Here we describe a means to predict the binding preferences of MHC proteins: We have developed a model positional scanning library analysis (MPSLA) by harnessing the power of mixture based combinatorial libraries to probe the peptide landscapes of distinct MHC II DQ proteins. The algorithm provided by NNAlign was employed to predict the binding affinities of sets of peptides generated for DQ proteins. These binding affinities were then used to retroactively construct a model Positional Scanning Library screen. To test the utility of the approach, a model screen was compared to physical combinatorial screens for human MHC II DP. Model library screens were generated for DQ proteins derived from sequence data from bottlenose dolphins from the Indian River Lagoon (IRL) and the Atlantic coast of Florida, and compared to screens of DQ proteins from Genbank for dolphin and three other cetaceans. To explore the peptide binding landscape for DQ proteins from the IRL, combinations of the amino acids identified as active were compiled into peptide sequence lists that were used to mine databases for representation in known proteins. The frequency of which peptide sequences predicted to bind the MHC protein are found in proteins from pathogens associated with marine mammals was found to be significant (p values <0.0001). Through this analysis, genetic variation in MHC (classes I and II) can now be associated with the binding repertoires of the expressed MHC proteins and subsequently used to identify target pathogens. This approach may be eventually applied to evaluate individual population and species risk for outbreaks of emerging diseases.
Head and Neck Manifestations of Systemic Disease.

Systemic diseases commonly managed by the Internist may have presentations within the head and neck. Awareness of these manifestations, sometimes as the presenting signs or symptoms of systemic disease, may aid the Internist in diagnosis and management. The Otolaryngologist may be helpful in assisting in the evaluation of these patients and in some cases providing targeted symptomatic therapy. Some systemic processes can generate emergent airway events, and early engagement of the otolaryngologist is of value.
A Randomized Trial of an Online Risk Reduction Intervention for Young Black MSM

HealthMpowerment.org (HMP), is a mobile optimized, online intervention to reduce sexual risk behaviors among HIV-positive and HIV-negative young Black men who have sex with men (BMSM) by providing information and resources, fostering social support, and including game-based elements. A randomized controlled trial with 474 young BMSM compared HMP to an information-only control website. The rate of self-reported condomless anal intercourse (CAI) at 3-months was 32% lower in the intervention group compared to the control group (IRR 0.68, 95% CI 0.43, 0.93), however this effect was not sustained at 12 months. Among HIV-positive participants, the rate of CAI at 3-month follow-up was 82% lower among participants with detectable viral loads in the intervention group compared to the control group (IRR 0.18, 95% CI 0.04, 0.32). In a secondary analysis, when we limited to those who used HMP for over 60 min during the 3-month intervention period (n = 50, 25.8%), we estimated 4.85 (95% CI 2.15, 7.53) fewer CAI events than we would have expected in control participants, had they used the intervention at the same rate as the intervention group. Findings suggest that exposure to an online intervention can reduce the rate of CAI among young BMSM, at least in the short term. Given the stronger effect seen among those participants who complied with HMP, additional intervention engagement strategies are warranted.
High surface-area carbon microcantilevers

Microscale porous carbon mechanical resonators were formed using carbon nanotube templated microfabrication. These cantilever resonators exhibited nanoscale porosity resulting in a high surface area to volume ratio which could enable sensitive analyte detection in air. These resonators were shown to be mechanically robust and the porosity could be controllably varied resulting in densities from 102 to 103 kg m−3, with pore diameters on the order of hundreds of nanometers. Cantilevers with lengths ranging from 500 μm to 5 mm were clamped in a fixture for mechanical resonance testing where quality factors from 102 to 103 were observed at atmospheric pressure in air.
Governing Authoritarian Law: Law as Security

What is the Singapore model of governance when it comes to law? In this chapter, I focus on a persistent strand of Singapore governance practices and discourses on law: the state’s insistence that ‘the people’ imperil the state. Understanding ‘the people’ both as individuals and as collectives, I argue that the Singapore model is to contain and govern the scope and rights-bearing meanings of law, by subordinating law to techniques, ideologies, and practices of an alternative category and logic: security. Through Singapore-specific articulations, law becomes a cipher for security, and, as a national-legal project, security privileges state perspectives and policies. In the course of the national-legal project of security, ‘the people’—their narratives, beliefs, and identities—become subsumed to governance oriented to strengthening the state.
KE EMu and the Future for Natural History Collections

This paper describes the current status and the future outlook for KE EMu, a system for museum collection documentation and management that is capable of monitoring collections and exporting data t...