cssi/SciSciGPT-SciSciNet huggingface dataset:
Direct Interaction of RIC-3 with the Intracellular Domain of Eukaryotic Cationic Pentameric Ligand-Gated Ion Channels

Eukaryotic pentameric ligand-gated ion channels (pLGIC) represent targets for a wide variety of drugs such as skeletal muscle relaxants, anti-psychotics, anti-epileptics and drugs against Parkinson's and Alzheimer's diseases. Each subunit consists of an extracellular domain (ECD), a transmembrane domain (TMD) with 4 α-helical segments, and an intracellular domain (ICD) that is 4-14 amino acids long in prokaryotes and ∼50-270 amino acids in eukaryotes. The ICD of eukaryotes has been implicated in modulating single channel conductance and kinetic properties of the channel. Additionally, it interacts with cytosolic proteins such as the resistance to inhibitors of cholinesterase protein, RIC-3, that affects plasma membrane-expression of some pLGIC. We created chimeras by introducing the ICD of cationic (5-HT3A , nACh α7) as well as anionic (Glycine α1, GABAA ρ1) eukaryotic pLGICs into the Gloeobacter violaceus pLGIC, GLIC, a well-studied prokaryotic homologue, that only contains ECD and TMD. Electrophysiological experiments after X. laevis oocyte expression (EC50 and IC50) demonstrate that for each of the four chimera sets, we have constructs that act as functional proton-gated ion channels, similar to the parent GLIC. Co-expression of cationic chimeras as well as wild-type pLGIC together with RIC-3 showed significant changes in current amplitudes, whereas RIC-3 did not affect anionic receptor chimeras or wild-type channels. We established that cationic chimeras and RIC-3, both overexpressed and purified to homogeneity from E. coli, bind to each other. Currently, we are using the chimeras to identify interacting proteins in native brain lysates. Our results clearly demonstrate a direct interaction between the ICD of cationic pLGIC and RIC-3. Specific interaction points will be identified in further studies.
Oscillations in age-structured population models with an Allee effect

A nonautonomous ordinary differential delay equation for the birth rate of a model age-structured population is derived under the assumptions that nonlinear density effects on fertility exhibit an “Allee effect”. It is shown how this assumption produces an interval of inherent net reproductive numbers less than one on which there exist two stable (asymptotic) equilibria. Furthermore, in the presence of a maturation delay and a sufficiently narrow age-specific fertility window, numerical solutions show that a certain type of attracting, large amplitude “synchronous” oscillation can also exist on this interval. A heuristic argument is given for the existence of such oscillations using the model obtained when the length of the fertility window shrinks to zero.
Surface fractal computation and its application to immunofluorescent histochemical studies of calpain and calpastatin in PC12 cells

Abstract The purpose of this report is to present a method which can be used to parameterize patterns of immunofluorescent staining in cultured neural cells. The algorithm is based on the observation that the variance in pixel intensity of the image is a power function of the magnitude of the area in immunofluorescently stained PC12 cells. This property is used to derive the fractal dimension ( D ) of the region of interest (ROI), and corresponds to the complexity of the pixel intensity associated with the ROI, which is analogous to a fractal surface. We show that the measure is useful in characterizing immunofluorescent staining patterns, and apply this measure to study the effects of ethanol exposure on μ-calpain and calpastatin-associated immunoreactivity. Exposure of PC12 cells to ethanol (80 mM) × 48 h resulted in alterations in immunofluorescent signal (Control vs ethanol) associated with actin, calpastatin and μ-calpain: 2289 ± 166 vs 1709 ± 69, P P P D -values for the three proteins in the same order were: 2.32 ± 0.01 vs 2.31 ± 0.03, NS; 2.31 ± 0.01 vs 2.32 ± 0.01, NS; 2.16 ± 0.03 vs 2.24 ± 0.02, P D -value range of 2–3.
Performance comparison of an anamorphic spatial heterodyne spectrometer with conventional spectrometer

This article describes the modeling of the generic spatial heterodyne spectrometer, which resembles a somewhat modified Michelson interferometer. The power spectrum of the input source is determined by performing a one dimensional Fourier transform on the output intensity profile captured by a linear array detector. In order to illustrate the techniques employed in the modeling, an example of a heterodyne interferometer is developed and a comparison undertaken between its performance and that of a conventional spectrometer. Unlike the traditional FTIR system, the heterodyne spectrometer has the very desirable feature of having no moving components.
Cognitive influences on perceived change in social support, motivation, and symptoms of depression

In settings ranging from informal conversation to medical interviews and surveys, people are often asked to judge changes in subjective states that are important to them, such as perceived social support, motivation to cope with a negative life event, and symptoms of depression. How accurate are such reports, and are there theories of cognitive processes that can predict the most likely types of misperception? To address these questions, self-report survey data were collected from 224 recently unemployed adults. The measures assessed current subjective states of self and social environment at two times, separated by 4 months. Among the results, persons with high self-esteem were particularly likely to underestimate changes for the worse between the two survey waves-evidence of an optimistic response bias. When the dimension being judged was unstable and ambiguous, people were more likely to overestimate improvement-evidence of an optimistic response style. The findings were evaluated in terms of alternate theories of cognitive bias and in terms of implications for subsequent studies and application. Language: en
Looking into Our Organizational Soul on the 50th Anniversary of the SSSP: Rethinking Our Future and Reinventing Our Commitment to Social Justice

© 2001 by Society for the Stud y of Social Problems, Inc. All r ights r eserved. Send requests for permission to r epr int to: Rights and Per missions, Univer sity of Califor nia Press, Journals Division, 2000 Center St., Ste. 303, Ber keley, CA 94704-1223. Looking into Our Organizational Soul on the 50th Anniversary of the SSSP: Rethinking Our Future and Reinventing Our Commitment to Social Justice
Mental visualization of objects from cross-sectional images

We extended the classic anorthoscopic viewing procedure to test a model of visualization of 3D structures from 2D cross-sections. Four experiments were conducted to examine key processes described in the model, localizing cross-sections within a common frame of reference and spatiotemporal integration of cross sections into a hierarchical object representation. Participants used a hand-held device to reveal a hidden object as a sequence of cross-sectional images. The process of localization was manipulated by contrasting two displays, in situ vs. ex situ, which differed in whether cross sections were presented at their source locations or displaced to a remote screen. The process of integration was manipulated by varying the structural complexity of target objects and their components. Experiments 1 and 2 demonstrated visualization of 2D and 3D line-segment objects and verified predictions about display and complexity effects. In Experiments 3 and 4, the visualized forms were familiar letters and numbers. Errors and orientation effects showed that displacing cross-sectional images to a remote display (ex situ viewing) impeded the ability to determine spatial relationships among pattern components, a failure of integration at the object level.
Coronary Revascularization before Noncardiac Surgery

The evaluation of cardiac risk before noncardiac surgical procedures and interventions aimed toward reducing that risk have become an integral part of the contemporary practice of medicine. In the ...
Suppression of Chemotactic Activity of Human Neutrophils by Streptolysin O

Human neutrophils were treated with streptolysin O in amounts that failed to cause cell lysis or morphologic changes. As a result of this treatment, the neutrophils were unable to respond to chemotactic factors. The inhibition of chemotaxis by streptolysin O was independent of factors in serum and could be prevented by heat inactivation, oxidation, and serum containing antistreptolysin O if used in sufficient titer with prior incubation. In addition to preventing directional mobility of leukocytes, streptolysin O also suppressed the random migration of neutrophils.
Atelopidtoxin from the Panamanian frog, Atelopus zeteki.

Abstract A water soluble, dialyzable toxin from the skin of the Panamanian frog, Atelopus zeteki , has been partially purified by a combination of dialysis, gel filtration, cellulose column chromatography and precipitation from water with acetone. This toxin, designated atelopidtoxin, at its present state of purity has a ld 50 (i.p., mice) of about 0·016 mg per kg, and thus has a toxicity which is only slightly less than the most lethal non-protein toxins known. When injected into mammals it produces hypotension and ventricular fibrillation. Its chemical and pharmacological properties exclude the possibility that it is batrachotoxin, isobatrachotoxin, tetrodotoxin or saxitoxin, the only known non-protein toxins which are more lethal than atelopidtoxin.
A STUDY OF DIVERSE HUMORAL ANTIBODY SYSTEMS FOLLOWING A SINGLE INJECTION OF FREUND'S INCOMPLETE ADJUVANT.

Abstract A wide spectrum of humoral antibody systems has been evaluated in thirty-one patients before and after they received a single placebo injection of saline solution emulsified with an Arlacel-Drakeol mixture. Certain liver function parameters and antitissue antibodies were also investigated at the same time. There were no significant alterations in viral, bacterial, or pollen antibody titers following this injection. Tests for rheumatoid activity, lupus factor, and antitissue antibodies were negative, and liver function was not affected by the subcutaneous deposition of emulsion. These results indicate that the clinical effects of oily repository materials are not mediated by a nonspecific anamnestic type of response. They also suggest that oily emulsions are apparently not hazardous to certain vital organs, at least within a one-month period after administration.
Estimates of adherence and error analysis of physical activity data collected via accelerometry in a large study of free-living adults

Activity monitors (AM) are small, electronic devices used to quantify the amount and intensity of physical activity (PA). Unfortunately, it has been demonstrated that data loss that occurs when AMs are not worn by subjects (removals during sleeping and waking hours) tend to result in biased estimates of PA and total energy expenditure (TEE). No study has reported the degree of data loss in a large study of adults, and/or the degree to which the estimates of PA and TEE are affected. Also, no study in adults has proposed a methodology to minimize the effects of AM removals. Adherence estimates were generated from a pool of 524 women and men that wore AMs for 13 – 15 consecutive days. To simulate the effect of data loss due to AM removal, a reference dataset was first compiled from a subset consisting of 35 highly adherent subjects (24 HR; minimum of 20 hrs/day for seven consecutive days). AM removals were then simulated during sleep and between one and ten waking hours using this 24 HR dataset. Differences in the mean values for PA and TEE between the 24 HR reference dataset and the different simulations were compared using paired t-tests and/or coefficients of variation. The estimated average adherence of the pool of 524 subjects was 15.8 ± 3.4 hrs/day for approximately 11.7 ± 2.0 days. Simulated data loss due to AM removals during sleeping hours in the 24 HR database (n = 35), resulted in biased estimates of PA (p < 0.05), but not TEE. Losing as little as one hour of data from the 24 HR dataset during waking hours results in significant biases (p < 0.0001) and variability (coefficients of variation between 7 and 21%) in the estimates of PA. Inserting a constant value for sleep and imputing estimates for missing data during waking hours significantly improved the estimates of PA. Although estimated adherence was good, measurements of PA can be improved by relatively simple imputation of missing AM data.
Self-Interest, Sympathy And The Origin Of Endowments

We explore whether the recent laboratory findings that suggest the origin of endowment matters in simple bargaining games are actually due to contextual shifts of relative effort and deservingness. Results support previous findings of endowment origin yielding more self-interested behavior.
Enhancing interfacial conductivity and spatial charge confinement of LaAlO3/SrTiO3 heterostructures via strain engineering

We explored the possibility of enhancing interfacial conductivity and spatial charge confinement of LaAlO3/SrTiO3 (LAO/STO) heterostructure (HS) via strain engineering using first-principles electronic structure calculations. We found that applying a tensile strain on the STO substrate along the ab-plane can significantly enhance the interfacial conductivity, magnetic moments, and the spatial charge confinement of the HS system. In contrast, a compressive strain can dilute the interfacial charge carrier density, make the mobile charges transfer to deep STO substrate, and weaken the spatial charge confinement along the c-axis. Hence, we propose that applying a tensile strain can be an effective way to enhance the interfacial conductivity and magnetism of STO-based HS systems.
Phase transformation of BeS and equation-of-state studies to 96 GPa

We report the existence of a reversible first-order phase transition of BeS from the zinc-blende structure, $B3,$ to the nickel-arsenide structure, $B8,$ at 51 GPa with a volume change of 11%. The NiAs phase remains stable up to at least 96 GPa. A second-order Birch equation describes the equation of state of the $B3$ phase with ${B}_{o}=105\mathrm{GPa}$ and ${B}_{o}^{\ensuremath{'}}=3.5.$ Preliminary studies of BeO to 66 GPa are described.
Crystal structure of the yeast nicotinamidase Pnc1p

The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the histone deacetylase Sir2p. The Pnc1p structure was determined at 2.9A resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni(2+)-coupled chromatography resins. Researchers expressing histidine-tagged proteins in yeast should be aware of the propensity of Pnc1p to crystallize, even when overwhelmed in concentration by the protein of interest. The protein assembles into extended helical arrays interwoven to form an unusually robust, yet porous superstructure. Comparison of the Pnc1p structure with those of three homologous bacterial proteins reveals a common core fold punctuated by amino acid insertions unique to each protein. These insertions mediate the self-interactions that define the distinct higher order oligomeric states attained by these molecules. Pnc1p also acts on pyrazinamide, a substrate analog converted by the nicotinamidase from Mycobacterium tuberculosis into a product toxic to that organism. However, we find no evidence for detrimental effects of the drug on yeast cell growth.
CogTeach: Teaching Residents to Communicate with Older Patients Who Have Mild Neurocognitive Disorder

Introduction: Woodgreen is a large community social services provider in Toronto, Canada delivering a range of services from supportive housing to counselling. Geriatric psychiatry services as delivered in the formal health care system can be difficult to access for marginalized populations. A model of integrated geriatric mental health care was developed with Woodgreen to allow for staff education, clinics delivered at the Woodgreen offices, and home visits. Methods: We describe a year’s experience in developing and delivering an integrated geriatric mental health model of care. A qualitative approach was taken to describe staff and patient experience, and a quantitative approach used to describe the patient population served. Results: Careful stepwise engagement with staff and the community was essential in gaining trust and enabling a close working relationship with case managers and front-line workers who had not previously worked with geriatric psychiatry or who had negative experiences with the formal health care system. Qualitative data indicate significant staff appreciation for ongoing education and support and for relatively rapid access to geriatric psychiatry consultation, quantitative data indicate that the patient population served simply would not have received geriatric psychiatry care otherwise. The program was also helpful in facilitating access of socially isolated elders with complex psychiatric and medical problems to the health care system. Conclusions: Embedding a geriatric psychiatry outreach service within community social service provider can be an effective means of increasing access to mental health care for a frail elderly population. Careful attention to building trust at the outset of the partnership between different care providers (ie. geriatric psychiatry and the community agency) was essential in making this program a success.
Acoustic streaming in a rotating fluid

Acoustic streaming theory is derived that is applicable to a fluid that is slow moving in a reference frame that rotates with a constant angular velocity Ω. A simplified streaming equation is obtained for the special case in which the acoustic angular frequency ω is large relative to Ω, and the change in fluid density due to rotation alone is negligible. For this special case it is shown that the ‘‘driving force’’ for the acoustic streaming is independent of Ω. Thus if no acoustic streaming is present in a fluid system that is stationary, then no steady‐state acoustic streaming is predicted for a similar system that rotates with constant angular velocity. For a system in which acoustic streaming is present, the flow behavior depends on the relative magnitudes of the Coriolis forces and the viscous forces. If the Ekman number is large (that is, the viscous force dominates) then the predicted flow is identical to that which would exist in a stationary system. If, on the other hand, the Ekman number is small then the Coriolis force dominates and the component of flow in the direction of the axis of rotation can be much smaller in the rotating system than in a similar system at rest.
RELATION OF DEPRESSION AND VERBAL INTERACTION IN GROUP THERAPY

Stdnzmary.-In order to test a hypothesized relationship bemeen depression and NO objective measures of verbal participation in group therapy, interaction recording was done for each session of two ongoing therapy groups over a 2-mo. period. Each patient, at che end of each group session, filled out the Depression Adjective Checklist. Correlations berween checklist scores and objective interaction measures for individual patients and for groups over sessions were not significant. The negative findings were interpreted as evidence that within-session characteristics of 3 group and the therapist have more influence on interaction patterns than do moderate fluctuations in affect level. Although more and more attention is being given to group psychotherapy (Corsini & Putzey, 1956; Lubin & Lubin, 1966), little attention has been directed toward some of the more objective aspects of group interaction. Objective measures have revealed the effects of differences between therapists (Grosz, Stern, & Wright, 1965), the influence of the therapist's participation (Dinoff, Hornet, Kurpiewski, & Timmons, 1960; Holrnes, 1966; Salzberg, 1961, 1962), and the relation between personality measures and social interaction (Stern & Grosz, 1966). The current study was designed to investigate the relation of depression as measured by Form F of the Depression Adjective Checklist (DACL; Lubin, 1967) and cwo objective measures of patient interaction in groups. Behavioral concomitants of clinically-observed depression were expected to produce a lowered frequency of interaction and a shorter total interaction time in those patients who scored as more depressed on the DACL. METHOD Twenty-one male, acute psychiatric inpatients were seen in two different open therapy groups. Although a maximum of six patients were present for any one group session, over the 3-mo. duration of the snidy, 12 had been members of one group and 9 had participated in the other. The DACL, Form F, was the commercially-available version of the test. Interaction recording required an observer who operated buttons connected to electric counters. Available data included number of comments and total comment duration for each patient in the group and for the therapist. Each group was direcred by a different therapist, and each group met once per week for 11/' hhr. Both groups were ongoing when the st~~dy began. - ~p
Towards an adaptive Kanban system

SUMMARY This paper presents a control methodology for flow shops that is decentralized and adaptive in nature, and has low data handling and computational requirements. The methodology is based on stochastic automata methods for modelling learning behaviour. It is proposed that such a methodology can be used with Kanban type control technique to make flow shop systems more flexible and adaptive in nature, Relationship of the control model to computational models such as neural computing is discussed.
Friendship choices of multiracial adolescents: Racial homophily, blending, or amalgamation?

Using the National Longitudinal Study of Adolescent Health (Add Health), we utilize the concepts of homophily, blending, and amalgamation to describe the possible friendship patterns of multiracials. Homophily occurs when multiracials are most likely to choose other multiracials as friends. Blending occurs when friendship patterns of multiracials are somewhere in-between those of their monoracial counterparts. Amalgamation consists of friendship patterns that are similar to one of their monoracial counterparts. All groups exhibit signs of amalgamation such that non-white multiracials resemble Blacks, and White multiracials resemble whites except for Black-White multiracials. Black-Whites, Asian-Whites, and Asian-Blacks also exhibit signs of blending, while only Native American multiracials show signs of homophily. Multiracials have different experiences depending on their specific racial composition, and while they seem to bridge the distance between racial groups, their friendship patterns also fall along Black and White lines.
ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.

Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factors that drive different cellular lineages. Several histone modifications have been associated with gene silencing, including H3K27me3 and H3K9me3. We have previously shown that genes for the two largest classes of mammalian transcription factors are marked by distinct histone modifications; homeobox genes are marked by H3K27me3 and zinc finger genes are marked by H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved in mediating the H3K9me3 silencing mark. We have used ChIP-chip and ChIP-seq to demonstrate that SETDB1, but not G9a, is associated with regions of the genome enriched for H3K9me3. One current model is that SETDB1 is recruited to specific genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in turn recruited to the genome via interaction with zinc finger transcription factors that contain a Kruppel-associated box (KRAB) domain. However, specific KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger domains), can interact with KAP1 both in vivo and in vitro and, using ChIP-seq, we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at the 3′ ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide the first identification of a KRAB domain-containing ZNF that is involved in recruitment of the KAP1 and SETDB1 to specific regions of the human genome.
Anticonvulsant prophylaxis in neurological surgery

Seizures complicate many neurosurgical diseases and, in many situations, their prevention is desirable. In an attempt to arrive at a rational approach to the purely prophylactic administration of anticonvulsants, existing data pertaining to four topics were examined: the danger posed by a single seizure, the incidence of seizures in a given disease state, the ability of anticonvulsant medication to prevent seizures, and the risks and benefits associated with pharmacological intervention. In general, where the risk of seizure exceeds 10 to 15% or where a single seizure may have disastrous consequences, anticonvulsant prophylaxis is recommended.
Salt and wounds: a new mechanism for neuropathic pain

Neuropathic pain syndromes such as phantom limb pain have remained enigmatic to patients, physicians and researchers alike. A new study reveals how nerve damage may alter the pain threshold and lead to such syndromes.
The Nature and Significance of Kuznets Cycles

Both are generalizations of apparently irregular behavior. Total output rarely rises or falls at the same rate for two consecutive months, and it seldom moves in the same direction for many months together. These irregular movements, however, are not without pattern. The month-to-month movements are, for periods of time, predominantly upward, and these periods of expansion are succeeded by other periods in which movements are predominantly downward. These are the business cycles of capitalist economic life. They are fluctuations of aggregate output in which other aspects of economic activity join; they are widely diffused through the many sectors of the economy; and they recur at intervals which are as long as ten to twelve years but are normally less than five or six. And when we consider periods longer than those of business cycles, there emerges a persistent underlying tendency for output to rise. Although the rate of growth is not constant, the average level of output during any business-cycle period is normally higher than that attained during the preceding cycle period. The persistence of growth is one characteristic of the primary secular trend of output in capitalist countries in the era of industrialization.
The Visionary Experience in North American Shamanism

One unique feature found in many of the traditional Native American cultures in North America is that they socially sanction visionary experiences in individuals. How the visionary experience is used in these cultures and, in particular, in shamanism, is discussed. It is suggested that the process of using induction techniques for visionary experiences, in order to acquire shamanic power, may over time have an adverse affect on the shaman's ability.
Home made big data‽ Challenges and opportunities for participatory social research

Why should big data be the purview of only national governments, corporations, and (sometimes) academics? Many Web communications and other electronic traces are made by people as part of their everyday lives, and many of these same producers of big data have questions they want to answer about their own lives. This paper suggests some ways of thinking about big data in the context of questions people are trying to answer for themselves and their communities. It then takes an initial glance at conversations on Reddit to see how users draw on evidence, and concludes by arguing that there is space for home–made big data.
The culture of academic medicine: faculty perceptions of the lack of alignment between individual and institutional values.

BACKGROUND Energized, talented faculty are essential to achieving the missions of academic medical centers (AMCs) in education, research and health care. The alignment of individuals’ values with workplace experiences are linked to meaningfulness of work and productivity.
Recurrent seizure-related injuries in people with epilepsy at a tertiary epilepsy center: A 2-year longitudinal study

Though seizure-related injuries (SRIs) among people with epilepsy (PWE) have recently gained much attention in the literature, most studies are retrospective and data are gathered indirectly through questionnaires or medical record documentation. We investigated SRIs and their associated risks in PWE attending a tertiary care center with direct and systematic inquiries during routine clinic follow-up visits over a 2-year period (N = 306). Past SRIs occurred in 54% of all patients, and 24% experienced recurrent SRIs during the study period. On multiple regression analyses, past SRI was associated with tonic-clonic seizures (TCSs) (3.2, 95% CI = 1.7-5.8) and cognitive handicap (4.3, 95% CI 1.5-16.1), and recurrent SRI was associated with TCSs (3.5, 95% CI = 1.6-7.9). Most recurrent SRIs (72%) involved head injury. SRIs are common when assessed systematically in a tertiary care setting, and TCSs represent a risk factor for recurrent SRIs. The potential clinical impact of recurrent SRIs on PWE requires further study.
Characterization and quantification of biological micropatterns using Cluster-SIMS.

Micropatterning is used widely in biosensor development, tissue engineering and basic biology. Creation of biological micropatterns typically involves multiple sequential steps which may lead to cross-contamination and contribute to suboptimal performance of the surface. Therefore, there is a need to develop novel strategies for characterizing location-specific chemical composition of biological micropatterns. In this paper, C 60 + time-of-flight secondary ion mass spectrometry (ToF-SIMS) operating in the event-by-event bombardment/detection mode was used for spatially resolved chemical analysis of micropatterned indium tin oxide (ITO) surfaces. Fabrication of the micropatterns involved multiple steps including self-assembly of poly(ethylene glycol)-silane (PEG-silane), patterning of photoresist, treatment with oxygen plasma and adsorption of collagen (I). The ITO surfaces were analyzed with 26-keV C 60 + SIMS run in the event-by-event bombardment/detection mode at different steps of the modification process. We were able to evaluate the extent of cross-contamination between different steps and quantify coverage of the immobilized species. The methodology described here provides a novel means for characterizing the composition of biological micropatterns in a quantitative and spatially resolved manner.
Enzyme Processing Using Ultrafiltration Membranes

In the past several years there has been a continual increase in the use of ultrafiltration (UF) membranes for concentrating, separating, and purifying various dissolved solutes. The forecast in membrane separation processes as reported by Pattison (1968) will amount to $7.5 million by 1975. Of this total, it was estimated that $37.5 million will be spent in UF processes for industrial, medical, and surgical operations. Parallel in time with membrane-technology development is the increased usage of various enzyme preparations. Specifically, the use of enzymes in laundry detergents has caught the fancy of housewives in the past 2 years. Although the enzyme industry in the United States is by no means new, the recent innovation of enzyme additives in detergents has contributed significantly to the total market. For example, the total U. S. enzyme market in 1968 amounted to approximately $40 million, of which approximately $9 million was for laundry products (Anon., 1969A). However, the latter is expected to increase to $25 to $30 million in 1969 (Anon., 1969B).
Large-scale circulation anomalies conducive to extreme precipitation events and derivation of daily rainfall in northeastern Mexico and southeastern Texas

The severe impacts of climate variability and climate hazards on society reveal the increasing need for improving regional- and local-scale climate diagnosis. A new downscaling approach for climate diagnosis is presented here. It is based on artificial neural network (ANN) techniques that derive relationships from the largeand local-scale atmospheric controls to the local winter climate. This study documents the large-scale conditions associated with extreme precipitation events in northeastern Mexico and southeastern Texas during the 1985‐ 93 period, and demonstrates the ability of ANN to simulate realistic relationships between circulation‐humidity fields and daily precipitation at local scale. The diagnostic model employs a neural network that preclassifies the winter circulation and humidity fields into different patterns. The results from this neural network classification approach, known as a self-organizing map (SOM), indicate that negative (positive) anomalies of winter precipitation over the study area are associated with 1) a weaker (stronger) Aleutian low, 2) a stronger (weaker) North Pacific high, 3) a negative (positive) phase of the Pacific‐North American pattern, and 4) cold (warm) ENSO events. The atmospheric patterns classified with the SOM technique are then used as input to another neural network (feed-forward ANN) that captures over 60% of the daily rainfall variance over the region. This further reveals that the SOM preclassification of days with similar atmospheric conditions succeeded in emphasizing the differences of the atmospheric variance that are conducive to extreme precipitation. This resulted in a downscaling model that is highly sensitive to local- and large-scale weather anomalies associated with ENSO warm events and cold air outbreaks.
Site Design and Pedestrian Travel

Research findings are summarized regarding the relationship between site design and pedestrian travel in mixed-use, medium-density environments, and recommendations are set forth for improving pedestrian facilities in suburban neighborhoods. A quasi-experimental method is used to study pedestrian volumes into 12 neighborhood commercial centers in the central Puget Sound region. Sites were matched for population density, land use mix, and income, but they varied in terms of neighborhood site design as measured by block size, and by the length and completeness of sidewalk systems. Urban sites with small blocks and extensive sidewalk systems were found to have, on average, three times the pedestrian volumes of suburban sites with large blocks and short, incomplete sidewalk systems. There are, however, many suburban pedestrians, with volumes varying between 50 and 103 people per hour walking into the suburban commercial centers studied. The majority of suburban pedestrians use streets with sidewalks where ava...
Diversification in the Academic Workforce: The Case of the US and Implications for Europe

This paper examines two broad dimensions of change in the American academic profession: (1) demographic and generational change, including increasing feminization, changing attitudes toward the career-family balance, migration of faculty positions to the professions (versus the liberal arts) and away from the research university sector; and (2) changes in types of appointments, work and career tracks, including the decline of tenure and the rise of fixed term appointments, which involve more ‘specialized’ and less ‘place-bound’ work roles and alternative career tracks. It considers these changes more broadly in the context of the changing nature of work in a globalized economy and the changing nature of the knowledge industry and in the context of similar developments in Europe and Asia. It concludes with an extrapolation of how these trends are likely to play out in the US context and in a new ‘globalized’ academic marketplace over the next 10–20 years.
A multiscale projection method for macro/microcrack simulations

We present a new multiscale method for crack simulations. This approach is based on a two-scale decomposition of the displacements and a projection to the coarse scale by using coarse scale test functions. The extended finite element method (XFEM) is used to take into account macrocracks as well as microcracks accurately. The transition of the field variables between the different scales and the role of the microfield in the coarse scale formulation are emphasized. The method is designed so that the fine scale computation can be done independently of the coarse scale computation, which is very efficient and ideal for parallelization. Several examples involving microcracks and macrocracks are given. It is shown that the effect of crack shielding and amplification for crack growth analyses can be captured efficiently. Copyright © 2007 John Wiley & Sons, Ltd.
Group I metabotropic glutamate receptor-mediated calcium signalling and immediate early gene expression in cultured rat striatal neurons.

Group I metabotropic glutamate receptors (mGluRs) are positively coupled to phospholipase C (PLC) via G α q -proteins and are expressed in the medium-sized projection neurons of striatum. To characterize the group I mGluR/PLC-sensitive modulation of intracellular Ca 2 + ([Ca 2 + ] i ) signalling, primary neuronal cultures were prepared from the striatum of E19 rat embryos or neonatal day-1 rat pups. Cytoplasmic Ca 2 + signals were examined with fura-2/AM at a signal cell level. After 17-18 days in culture, a profound Ca 2 + response consisting of two phases was induced in cultured striatal neurons following bath application of the selective group I agonist, 3,5-dihydroxyphenylglycine (DHPG). The [Ca 2 + ] i elevation was concentration- and time-dependent, and was blocked by coexposure to the group I antagonist, Ν-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), or the PLC inhibitor, U-73122, but not to the group II/III antagonist (RS)-α-methylserine-Ophosphate monophenyl ester (MSOPPE). A series of further pharmacological studies demonstrated that the initial spike-like transient was dependent on intracellular Ca 2 + mobilization through 1,4,5-triphosphate-sensitive stores, and the second long-lasting rise was dependent on extracellular Ca 2 + influx through N-methyl-D-aspartate (NMDA) receptors and especially L-type voltage-operated Ca 2 + channels. Lastly, using an immediate early gene c-fos as a report of inducible gene expression, the resultant [Ca 2 + ] i elevation contributes to DHPG-stimulated c-fos mRNA and Fos protein expression in striatal neurons as revealed by quantitative in situ hybridization and immunocytochemistry, respectively. These results demonstrate that group I mGluRs are able to affect Ca 2 + homeostasis at multiple levels and trigger Ca 2 + -sensitive gene transcription in striatal neurons.
An approach to natalizumab hypersensitivity: a case series of induction of tolerance:

Induction of tolerance protocols have been applied successfully to manage allergic reactions to many medications. Hypersensitivity reactions to natalizumab (TYSABRI®) have been recognized as a growing problem. In circumstances where a hypersensitivity reaction to a medication has occurred, but no suitable alternative exists, drug induction of tolerance protocols may be considered. Drug induction of tolerance protocols were performed in three patients with prior hypersensitivity reactions to natalizumab. All three patients tolerated the protocol without adverse reactions, allowing for the safe reintroduction of natalizumab. To conclude, this case series demonstrates success with an induction of tolerance procedure to a highly effective biological agent for multiple sclerosis, in patients with allergic reactions to natalizumab.
Calibration of polarimetric radar images using only image parameters and trihedral corner reflector responses

A technique that uses the radar return from natural targets and at least one trihedral corner reflector to calibrate compressed polarimetric radar data is described. Calibration for relative amplitude, relative phase, absolute amplitude, and system crosstalk is addressed. The crosstalk calibration method is based on the theoretical result that for natural targets with azimuthal symmetry the copolarized and crosspolarized components of the scattering matrix are uncorrelated, and the method does not require any external calibration targets to be deployed before imaging. Because compressed data are used, one is forced to model the transmitting and receiving systems as reciprocal. Even though the inferred transmit and receive matrices are not each simply related to the physical transmitter and receiver, the true Stokes matrix for each pixel in an image can be accurately determined by this approach. The method is illustrated by estimating the crosstalk parameters of the NASA/JPL aircraft for different types of terrain and for two frequencies. For the C-band system, the crosstalk is less than -20 dB for all ranges in the images. The crosstalk of the L-band system is a function of range, however, and may be as poor as -10 dB in the near range, leading to a noticeable distortion of the polarization signatures. >
Pharmacokinetics of anticancer drugs in children

Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.
PHYLOGENY AND FORELIMB DISPARITY IN WATERBIRDS

Previous work has shown that the relative proportions of wing components (i.e., humerus, ulna, carpometacarpus) in birds are related to function and ecology, but these have rarely been investigated in a phylogenetic context. Waterbirds including "Pelecaniformes," Ciconiiformes, Procellariiformes, Sphenisciformes, and Gaviiformes form a highly supported clade and developed a great diversity of wing forms and foraging ecologies. In this study, forelimb disparity in the waterbird clade was assessed in a phylogenetic context. Phylogenetic signal was assessed via Pagel's lambda, Blomberg's K, and permutation tests. We find that different waterbird clades are clearly separated based on forelimb component proportions, which are significantly correlated with phylogeny but not with flight style. Most of the traditional contents of "Pelecaniformes" (e.g., pelicans, cormorants, and boobies) cluster with Ciconiiformes (herons and storks) and occupy a reduced morphospace. These taxa are closely related phylogenetically but exhibit a wide range of ecologies and flight styles. Procellariiformes (e.g., petrels, albatross, and shearwaters) occupy a wide range of morphospace, characterized primarily by variation in the relative length of carpometacarpus and ulna. Gaviiformes (loons) surprisingly occupy a wing morphospace closest to diving petrels and penguins. Whether this result may reflect wing proportions plesiomorphic for the waterbird clade or a functional signal is unclear. A Bayesian approach detecting significant rate shifts across phylogeny recovered two such shifts. At the base of the two sister clades Sphenisciformes + Procellariiformes, a shift to an increase evolutionary rate of change is inferred for the ulna and carpometacarpus. Thus, changes in wing shape begin prior to the loss of flight in the wing-propelled diving clade. Several shifts to slower rate of change are recovered within stem penguins.
Our Changing View of Contamination

My years as a research scientist have encompassed industry, academia and now a government agency. I have had the opportunity to observe the general trends in pollution research in each of these areas and have a perspective that may be of interest to this conference. One of the testy debates between scientists, industrialists and enforcement officials dealing with pollution and pollution criteria is the definition of “zero” for specifying a contaminant in a “pure” product. The viability of such a definition applies equally to foods, drugs, the atmosphere and the marine environment.
Dynamic Elastic Electron Scattering III: Other Approaches

Besides the Bloch wave and multislice theories introduced in Chapters 2 and 3, there are several other theories on dynamic electron scattering. Each of these methods is convenient for some particular purpose. Chapter 4 introduces these theories, then establishes the equivalence among them.
Distinct forms of cytochrome P-450 are responsible for 6β-hydroxylation of bile acids and of neutral steroids

Cytochrome P-450-dependent 6 beta-hydroxylation of bile acids in rat liver contributes to the synthesis of the quantitatively important pool of 6-hydroxylated bile acids, as well as to the detoxification of hydrophobic bile acids. The lithocholic acid 6 beta-hydroxylation reaction was investigated and compared with androstenedione 6 beta-hydroxylation. Differential responses of these two activities to inducers and inhibitors of microsomal P-450 enzymes, lack of mutual inhibition by the two substrates and differential inhibition by antibodies raised against several purified hepatic cytochromes P-450 were observed. From these results it was concluded that 6 beta-hydroxylation of lithocholic acid is catalysed by P-450 form(s) different from the subfamily IIIA cytochromes P-450 which are responsible for the bulk of microsomal androstenedione 6 beta-hydroxylation. Similar, but more tentative, results revealed that the 7 alpha-hydroxylation of lithocholic acid and of androstenedione may be also catalysed by distinct P-450 enzymes. The results indicate that cytochromes P-450 hydroxylating bile acids are distinct from analogous enzymes that carry out reactions of the same regio- and stereo-specificity on neutral steroids (steroid hormones). A comparison of pairs of cytochromes P-450 that catalyse the same reaction on closely related steroid molecules will help to define those structural elements in the proteins that determine the recognition of their respective substrates.