cssi/SciSciGPT-SciSciNet huggingface dataset:
Do Drug Metabolism and Pharmacokinetic Departments Make Any Contribution to Drug Discovery

The alignment of drug metabolism and pharmacokinetic departments with drug discovery has not produced a radical improvement in the pharmacokinetic properties of new chemical entities. The reason for this is complex, reflecting in part the difficulty of combining potency, selectivity, water solubility, metabolic stability and membrane permeability into a single molecule. This combination becomes increasingly problematic as the drug targets become more distant from aminergic seven-transmembrane-spanning receptors (7-TMs). The leads available for aminergic 7-TMs, like the natural agonists, are invariably small molecular weight, water soluble and potent. Even moving to 7-TMs for which the agonist is a peptide invariably produces lead matter that is less drug-like (higher molecular weight and lipophilic). The role of drug metabolism departments, therefore, has been to guide chemistry to obtaining adequate, rather than optimal, pharmacokinetic properties for these ‘difficult’ drug targets. A consistent belief of many researchers is that a high value is placed on optimal, rather than adequate, pharmacokinetic properties. One measure of value is market sales, and when these are examined no clear pattern emerges. Part of the success of amlodipine in the calcium channel antagonist sector must be due to its excellent pharmacokinetic profile, but the best-selling drugs among the angiotensin antagonists and β-blockers have a much greater market share than other agents with better pharmacokinetic properties. Clearly, many other factors are important in the successful launch of a medicine, some reflected in the manner the compound is developed and the subsequent structure of the labelling. Overall, therefore the presence of drug metabolism in drug discovery has probably contributed most by allowing ‘difficult’ drug targets to be prosecuted, rather than by guiding medicinal chemists to optimal pharmacokinetics. These ‘difficult’ target candidates become successful drugs when skilfully developed. There is no doubt that skilful development relies heavily on drug metabolism and pharmacokinetic departments, in this case those with a clinical rather than a preclinical orientation.
EXPERIMENTAL TWO-BEAM EXCITATION OF ELECTRON OSCILLATIONS IN A PLASMA WITHOUT SHEATHS

Coherent standing waves of longitudinal electron oscilla tions were excited in a plasma by two independent oppositely directed electron beams at 65 ev, having no electrode sheaths. Strorg sinusoidal standing waves, with two loops between electrodes, were found at 550 Mc/sec only when both beams and the plasma were present. Taking the distance between the electrodes as a wavelength, the phase velocity was 1.10 x 10/sup 9/ cm/sec; the electron velocity of either beam was 0.48 x 10/sup 9/ cm/sec. A single-loop standing wave was established with a beam energy of 74 ev. With either one or two loops, the standing wave amplitude fell gradually to zero when the voltage was increased or decreased approximately 3 volts from the stated value. An oscillation frequency spectrum and the test apparatus arrangements are illustrated. (B.O.G.)
Inhibition of interferon-α/β induction by crystalline cadmium sulfide

The induction of interferon-α/β by Newcastle disease virus in L-929 cells was inhibited by pretreatment of the cell cultures with the crystalline form of cadmium sulfide. As little as 10 μg/ml of crystalline cadmium sulfide was sufficient to inhibit the induction of interferon. Cell viability was not affected by this treatment as measured by trypan blue dye-exclusion viability staining. Between 6 and 24 hr of preincubation with crystalline cadmium sulfide was required for significant inhibition of interferon induction.
A multimeric MR-optical contrast agent for multimodal imaging

We describe the design, synthesis and in vitro evaluation of a multimodal and multimeric contrast agent. The agent consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore and possesses high relaxivity, water solubility, and is nontoxic. The modular synthesis is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications.
Searching for analogical ideas with crowds

Seeking solutions from one domain to solve problems in another is an effective process of innovation. This process of analogy searching is difficult for both humans and machines. In this paper, we present a novel approach for re-presenting a problem in terms of its abstract structure, and then allowing people to use this structural representation to find analogies. We propose a crowdsourcing process that helps people navigate a large dataset to find analogies. Through two experiments, we show the benefits of using abstract structural representations to search for ideas that are analogous to a source problem, and that these analogies result in better solutions than alternative approaches. This work provides a useful method for finding analogies, and can streamline innovation for both novices and professional designers.
A study of the relationship between concept emphasis in high school biology textbooks and achievement levels

A two part study investigated any relationship between student achievement and textbook content as well as any impact of a national project's recommendations on textbook content. First, analyses of student responses to biological items on the 1977 National Assessment of Educational Progress's survey of science showed a direct, linear relationship between achievement level and concept emphasis in biology textbooks. Second, a comparison between biology textbooks, published a decade apart, indicated significant changes in the degree of emphasis placed on 10 commonly accepted conceptual areas. Closer examination revealed that change in the amount of emphasis in one conceptual area, Growth and Development, was responsible for the significant difference found. Generally, the recommendations of the biology project were not reflected in the newer textbooks.
UV Emission from General Lighting Lamps

(1995). UV Emission from General Lighting Lamps. Journal of the Illuminating Engineering Society: Vol. 24, No. 1, pp. 13-24.
Blood-finding strategy of a capillary-feeding sandfly, Lutzomyia longipalpis.

Abstract 1. 1. Salivary gland homogenates of adult female Lutzomyia longipalpis inhibited platelet aggregation induced by ADP and collagen. 2. 2. Apyrase (ATP diphosphohydrolase) activity was prominent, requiring Ca 2+ but not Mg 2+ and a pH optimum of 8.0. 3. 3. Human as well as rabbit hosts developed a well delimited erythema, evident 2–3 min after initial probing and lasting for as long as 2 days. Erythema, not accompanied by itching or swelling, developed in previously exposed hosts as well as in those not previously exposed to this insect. 4. 4. When injected intradermally into the shaved back of a rabbit, salivary gland homogenates induced marked erythema, even with 1 250 of a homogenized salivary gland. This erythema-inducing factor was insoluble in 90% ethanol and was destroyed by incubation with trypsin. 5. 5. These apyrase and erythema-inducing factors, together with short mouthpart stylets, appear to adapt Lutzomyia sandflies to feed on blood released from superficial skin capillaries.
Meteorological Conditions during Heat Waves and Droughts in the United States Great Plains

Abstract Summertime droughts and/or heat waves in the Kansas City area and their associated large-scale circulation patterns and land-surface moisture conditions are investigates, using climatological monthly mean surface data, rawinsonde data. Palmer drought severity indices, gridded monthly mean sea-level pressure data, and gridded 500 mb height data. Surface station data include monthly mean surface pressure, maximum/minimum temperature, temperature range, monthly total precipitation, dewpoint and relative humidity. Anomalies in monthly mean surface air temperature at Kansas City are used as a basis for objectively ranking the 276 months in the 92 summers, 1889–1980. The concentration of drought months in the decades of the 1910s, 1930s, and 1950s is evident. Many of the hot months during these periods exhibited negative anomalies in relative humidity, dewpoint, precipitation and Palmer index. Not all the hot summer months in the record at Kansas City appear to have been associated with drought (as def...
Polymer Mediated Interactions Between Myelin Lipid Bilayers

The axons of the central nervous system are covered by a multi-layered membrane which provides insulation and high electric signal conductivity to the axons. Swelling of the myelin sheaths is the hallmark of many neurological degenerative diseases like multiple sclerosis. Loss of the myelin membrane involves subtle changes in the interaction forces that hold the membrane stack together. These interaction forces are believed to have more than one origin, the major one arising from the dedicated protein -myelin basic protein (MBP) - which binds to, and bridges, the cytoplasmic sides of myelin membrane via electrostatic and hydrophobic interactions. It has been shown that deimination of MBP leads to a loss of adhesion between myelin membranes and ultimately to swelling of myelin. In the present study, we explored a new strategy that makes use of structured polymers to reverse the effects of loss of adhesion between myelin membranes. By controlling the chemical composition and architecture of the polymers, our results show that it is possible to enhance the adhesion between the membranes using different types of interaction forces like electrostatic forces, depletion forces, bridging forces or combinations of them. Neutral triblock copolymers with a central hydrophobic segment present a strong affinity to the bilayers and enhance the adhesive interaction forces between the membranes via a depletion mechanism similar to hydrophilic homopolymers (like PEG). On the other hand, triblocks copolymers with two hydrophobic lateral blocks promote adhesion between bilayers via bridging interaction controlled by the concentration and segments chain length of the polymer. The results pave a new route to the development of treatments for this debilitating disease and shed a new light on the relationship between polymer structure, self assembly and interactions with complex biomembranes.
Fault tolerant linear algebra: Recovering from fail-stop failures without checkpointing

Today's long running high performance computing applications typically tolerate fail-stop failures by checkpointing. While checkpointing is a very general technique and can be applied in a wide range of applications, it often introduces a considerable overhead especially when applications modify a large amount of memory between checkpoints. In this research, we will design highly scalable low overhead fault tolerant schemes according to the specific characteristics of an application. We will focus on linear algebra operations and re-design selected algorithms to tolerate fail-stop failures without checkpointing. We will also incorporate the developed techniques into the widely used numerical linear algebra library package ScaLAPACK.
Description and breeding behavior of two partial male sterile guar plants

This investigation describes two partial male sterile plants of guar, Cyamopsis tetragonoloba (L.) Taub. (MS-1 and MS-II), and gives results of their hybridization with a fertile cultivar. Detectable natural crossing between MS-1 plants and a fertile cultivar averaged 20.6%, with maximum crossing of 70 %. Crossing between MS-II plants and a fertile culuvar averaged 5.0 5.0 % about the same as previously reported for fertile × fertile, crosses. Honeybees, Apis mellifera (L.), caged with MS-II plants and a fertile cultivar did not increase seed set on male sterile plants. Hand separation of mature pods into short- and long-pod groups was only partially effective in identifying hybrid seed produced on the male sterile plants.
Comparison of strains transferred to a bone simulant between as-cast and postsoldered implant frameworks for a five-implant-supported fixed prosthesis.

Purpose To measure and compare the strains transferred by screw-fastening one-piece full-arch prostheses as cast and after sectioning and soldering. Materials and Methods Photoelastic resin was applied directly to five 3.75 × 13-mm Branemark implants, situated 7 mm apart, in a silicone mold of an edentulous mandible. Four strain gauge rosettes were also incorporated in the resin to allow strain measurements at four locations. Three frameworks were made from a single master cast produced from an impression of the five-implant model with 4-mm abutments. These frameworks were sequentially secured to the master model with five gold slot screws tightened to 10 N cm. Strain indicator readings were recorded at a standardized time following the initial fastening of each prosthesis. The test was repeated three times. Each of the three castings were subsequently sectioned and soldered in two locations, mesial to the two terminal fixtures. After soldering, the three superstructures were returned to the master model for measurement of postsolder strains three times each. A one-way repeated-measures ANOVA was performed to determine differences between mean principal strains between the as-cast and postsoldered groups. Results A statistically significant difference was found in the principal strains between the as-cast and soldered frameworks. Overall, there was a decrease in the magnitude of strain for the soldered frameworks. Conclusions Sectioning and soldering improved the as-cast accuracy as far as the amount of strain transferred to the bone simulant.
Kernel design for reduced interference distributions

The authors present a class of time-frequency signal representations (TFRs) called the reduced interference distribution (RID). An overview of commonly used TFRs is given, and desirable distribution properties are introduced. Particular attention is paid to the interpretation of Cohen's class of time-frequency distributions of TFRs in the ambiguity, temporal correlation, spectral correlation, and time-frequency domains. Based on the desirable kernel requirements, the RID is discussed and further defined. A systematic procedure to create RID kernels, (or, equivalently, compute RIDs) is proposed. Some aspects and properties of the RID are discussed. The authors estimate design considerations for RIDs and compare various selections of the primitive window. Some experimental results demonstrating the performance of the RID are presented. >
Accounting for Change in Declarative Memory: A Cognitive Neuroscience Perspective.

The medial temporal lobe memory system matures relatively early and supports rudimentary declarative memory in young infants. There is considerable development, however, in the memory processes that underlie declarative memory performance during infancy. Here we consider age-related changes in encoding, retention, and retrieval in the context of current knowledge about the brain systems that may underlie these memory processes. While changes in infants’ encoding may be attributed to rapid myelination during the first year of life, improvements in long-term retention and flexible retrieval are likely due to the prolonged development of the dentate gyrus. Future studies combining measures of brain and behavior are critical in improving our understanding of how brain development drives memory development during infancy and early childhood.
Climate change effects on historical range and variability of two large landscapes in western Montana, USA

Quantifying the historical range and variability of landscape composition and structure using simulation modeling is becoming an important means of assessing current landscape condition and prioritizing landscapes for ecosystem restoration. However, most simulated time series are generated using static climate conditions which fail to account for the predicted major changes in future climate. This paper presents a simulation study that generates reference landscape compositions for all combinations of three climate scenarios (warm-wet, hot-dry, and current) and three fire regime scenarios (half historical, historical, and double historical fire frequencies) to determine if future climate change has an effect on landscape dynamics. We applied the spatially explicit, state-and-transition, landscape fire succession model LANDSUM to two large landscapes in west-central Montana, USA. LANDSUM was parameterized and initialized using spatial data generated from the LANDFIRE prototype project. Biophysical settings, critical spatial inputs to LANDSUM, were empirically modeled across the landscape using environmental gradients created from historical and modeled future climate daily weather data summaries. Successional pathways and disturbance probabilities were assigned to these biophysical settings based on existing field data and extensive literature reviews. To assess the impact of changes in climate and fire regime, we compared simulated area burned and landscape composition over time among the different simulation scenario combinations using response variables of Sorenson's index (a global measure of similarity) and area occupied by the dominant vegetation class (simple indicator of change in landscape composition). Results show that simulated time series using future predicted climate scenarios are significantly different from the simulated historical time series and any changes in the fire regime tend to create more dissimilar and more variable simulated time series. Our study results indicate that historical time series should be used in conjunction with simulated future time series as references for managing landscapes.
What Do We Know about the Urinary Tract Infection–Prone Individual?

Host factors play a pivotal role in the balance between sterility and infection of the urinary tact. Bacteria enter the urinary tract from the fecal reservoir via ascent thorough the urethra into the bladder. Most episodes of pyelonephritis are caused by retrograde ascent of bacteria from the bladder through the ureter to the renal pelvis and parenchyma. Unobstructed flow of urine and washout of transient urothelial colonizers is an integral part of the host defense. Other host defenses include the antibacterial effect of urine; glycoproteins that block adherence of bacteria to the urothelial and vaginal mucosa; and immunologic responses, including immunoglobulins, leukocytes, and cytokines, that facilitate bacterial clearance. The extent of susceptibility to urinary tract infection (UTI) is governed by bacterial virulence factors and the magnitude of deficiencies in host defense (figure 1). Complicated infections are associated with anatomic, functional, or metabolic abnormalities of the urinary tract that disable the natural defenses and lead to significant destruction of renal tissue. Uncomplicated infections are associated with more subtle, variable alterations governed by genetic, biologic, and behavioral or environmental factors that promote bacterial access to and colonization/infection of the urinary tract.
Adaptive on-chip power supply with robust one-cycle control technique

In this paper, an integrated adaptive output switching converter is proposed. The design uses a one-cycle control for fast line regulation and a single outer loop for load regulation and fine tuning. A switched-capacitor integrator is introduced in the one-cycle control to obtain positive integration with a single positive power supply, allowing a standard low-cost CMOS fabrication process. To improve the efficiency, a dynamic loss control technique is presented. HSPICE simulations are performed with transistor models from TSMC 0.35mum N-well CMOS fabrication process. With a supply voltage of 3 V, a voltage ripple of less than 15 mV is measured. The maximum efficiency is 92% with a load power of 475 mW. The converter exhibits a tracking speed of 2 mus/V for both start-up and reference voltage transitions. The recovery time for a 20% load change is approximately 2.6mus. The overall design exhibits superior system robustness to battery perturbations, noise and process variations
Modelling courage: The role of dissent in fostering independence.

While dissent has been construed in terms of social support and informational influence, this paper hypothesizes that exposure to dissenting minority views, even when they are wrong, stimulates resistance to conformity and increased adherence to one's own views. In this study, individuals in groups of four judged the colour of a series of blue stimuli and were exposed to one individual who consistently judged the stimuli to be ‘green: inconsistently judged them to be 'green' or expressed no dissent. In a subsequent setting, when judging a series of red slides; subjects were exposed to a majority who repeatedly judged them as 'orange’. Exposure to dissent, whether it was consistent or inconsistent, substantially reduced the level of conformity. In fact, exposure to the consistent dissent led to almost complete independence.
Recycling inflow method for simulations of spatially evolving turbulent boundary layers over rough surfaces

ABSTRACTThe technique by Lund et al. to generate turbulent inflow for simulations of developing boundary layers over smooth flat plates is extended to the case of surfaces with roughness elements. In the Lund et al. method, turbulent velocities on a sampling plane are rescaled and recycled back to the inlet as inflow boundary condition. To rescale mean and fluctuating velocities, appropriate length scales need be identified and for smooth surfaces, the viscous scale lν = ν/uτ (where ν is the kinematic viscosity and uτ is the friction velocity) is employed for the inner layer. Different from smooth surfaces, in rough wall boundary layers the length scale of the inner layer, i.e. the roughness sub-layer scale ld, must be determined by the geometric details of the surface roughness elements and the flow around them. In the proposed approach, it is determined by diagnosing dispersive stresses that quantify the spatial inhomogeneity caused by the roughness elements in the flow. The scale ld is used for rescali...
Environmental regulation of plant gene expression: An RT-qPCR laboratory project for an upper-level undergraduate biochemistry or molecular biology course

We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the FLOWERING LOCUS C gene, a key regulator of floral timing in Arabidopsis thaliana plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate students in biochemistry or molecular biology courses. The project provides students with hands-on experience with RT-qPCR, the current "gold standard" for gene expression analysis, including detailed data analysis using the common 2-ΔΔCT method. Moreover, it provides a convenient starting point for many inquiry-driven projects addressing diverse questions concerning ecological biochemistry, naturally occurring genetic variation, developmental biology, and the regulation of gene expression in nature.
Effective design of electronic commerce environments: a proposed theory of congruence and an illustration

We posit that the current electronic commerce (EC) systems are not user-oriented. Consumers in an EC environment find it difficult to deal with the inherent nature of virtual reality in their interaction. We propose a conceptual framework to address such an issue by drawing on insights from contingency research in information systems design and media choice behavior. The basic theme of this model, called the congruence model, is that for an EC systems environment to have favorable impact on a consumer, the system must have a good fit with both the products/services that are sold/provided and the users it supports. An initial validity of this conceptual framework is demonstrated by working with a few product and user types. A detailed evaluation of eight different commercial web sites dealing with four different product categories provides additional support to the proposed theory. We expect our conceptual model to spur significant future research on this important phenomenon.
Genetic and Physiological Characterization of ohr, Encoding a Protein Involved in Organic Hydroperoxide Resistance in Pseudomonas aeruginosa

The ohr (organic hydroperoxide resistance) gene product of Pseudomonas aeruginosa was essential for optimal resistance to organic hydroperoxides (OHPs) but not to hydrogen peroxide or paraquat. A Δohr mutant was hypersusceptible to OHPs in disk inhibition assays and showed enhanced killing by OHPs in liquid culture. The ohr gene product was demonstrated to contribute to the decomposition of OHPs. Transcription of ohr was induced up to 15-fold upon exposure to OHPs, and this induction was independent of OxyR. Somewhat enhanced ohr-lacZ activity was detected in mutant strains affected in ohr, ahpC, and oxyR, and this phenotype correlated with hypersusceptibility to OHPs, suggesting overlapping or compensatory functions of the ohr and ahpC gene products. A single transcriptional start site for ohr was determined, and ohr transcripts were abundant in cells treated with a sublethal dose of OHPs but not in cells treated with paraquat. An 84-bp portion upstream of the ohr mRNA start site was sufficient for ohr induction by OHPs. Thus, the ohr gene appears to encode an antioxidant enzyme that is not part of the OxyR regulon yet is specifically induced by OHPs.
Local Understanding of Fish Consumption Advisory Risks in Michigan's Upper Peninsula: The Role of Structure, Culture, and Agency*

Fish consumption advisories fail to adequately help communities address the benefits and risks of eating potentially contaminated fish. We engaged community members and relevant institutions in identifying and implementing more effective risk communication in Michigan's rural Upper Peninsula. In 2004-2005, we collected data in four Michigan counties through focus groups, community dinners, public meetings and angler interviews. Residents express a strong affinity toward eating Great Lakes fish, though a minority of participants have read the official fish advisory. Participants lack an understanding of how bioaccumulation affects consumption risk depending on the type of contaminant. We attribute the situation to conditions of post-normal risk that emerge through interaction of the structural dimensions of science and bureaucracy with a strong natural resource-based culture that affects the agency of residents. The implications loom large as Michigan's Department of Community Health no longer distributes hard copies of the Michigan Fish Advisory.
Science as Storytelling for Teaching the Nature of Science and the Science-Religion Interface.

Here we describe a method for teaching the NOS called " Science as Storytelling, which was designed to directly confront na i¨ ve realist preconceptions about the NOS and replace them with more sop...
Forgetting the power of leaven: The historical method in recent New Testament theology

Ernst Troeltsch and Heikki Raisanen have raised significant challenges to the way New Testament theology handles the relation of history and theology. Troeltsch pushed Christian scholars to apply the historical method's three principles of criticism, analogy and correlation consistently to their work and thus embrace empiricism. Raisanen continues this trajectory by splitting New Testament theology into its descriptive and reflective tasks, resulting in a programme which questions the unity of the canon, the appropriateness of prescription and the role of church authority in New Testament theology. With these challenges in mind, this article examines four recent New Testament theologies to see how they use the historical method. It finds that these works exhibit different ad hoc ways of using the historical method, picking it up and setting it down at will. Peter Balla accepts New Testament theology as descriptive and historical while claiming it can also be theological by studying the content in the New Testament. Despite this embrace of the historical method, Balla remains uncomfortable with bare empiricism and pushes back on its naturalism. Georg Strecker splits the world into two: one part which can be investigated by the historical method and another part which lies outside its normal subject matter. The result is that he uses the historical method everywhere except where his main theological concern lies – Jesus’ resurrection. I. Howard Marshall similarly holds the historical method to be necessary for New Testament theology but largely ignores it in light of narrative-theological concerns. Frank Matera takes a purposefully literary approach to New Testament theology and generally ignores the historical method. He does invoke it, however, when the text becomes difficult and alternative readings must be found. The methodological inconsistency demonstrated by these New Testament theologies leads the article to conclude that this type of historical New Testament theology is a failed enterprise. A theological understanding of history based on work by Murray Rae is then proposed as an alternative which allows for methodological consistency in synthetic work on the New Testament.
Antigenic specificity of rheumatoid synovial fluid lymphocytes

The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone-precipitable MT antigenic complex (AP-MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti-CD3. In patients with RA, the SF proliferative responses to both TT and anti-CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP-MT was significantly increased, compared with PB. SF responses to AP-MT antigens were significantly greater than those to TT. The AP-MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP-MT responsiveness was not restricted to HLA-DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP-MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA.
Quantifying Southern Oscillation–Precipitation Relationships from an Atmospheric GCM

Abstract This paper is an extension of a study by C. Ropelewski and M. Halpert, which examines observed precipitation relationships with the Southern Oscillation. Here, the authors repeat their analysis using atmospheric general circulation model precipitation from the average of a 13-run ensemble. The GCM is the atmospheric component of the coupled model used for seasonal prediction at the National Centers for Environmental Prediction, except that in this study, the observed sea surface temperatures were specified for the ensemble runs. Results are compared and contrasted with the observed Southern Oscillation–related precipitation behavior. These comparisons show that the multiple ensemble simulations compare favorably to the observations for most areas in the Tropics and subtropics. However, outside of the deep Tropics, the model simulations show large shifts or biases in the location of the Southern Oscillation–related anomalies. In particular, anomalies shown by the observations to occur in the south...
The novel application of an immunological technique reveals the immunosuppressive effect of phytoestrogens in Betta splendens

The novel application of a standard technique to assess cell-mediated immune response to phytohaemagglutinin (PHA) injected in the caudal peduncle in a small fish (<2 g) to test the immunosuppressive effect of three phytoestrogens: genistein, equol and β-sitosterol is described. Individual Betta splendens exposed to these oestrogenic chemicals produced weaker inflammatory responses to PHA than did control individuals, suggesting that phytoestrogens are immunosuppressive. This technique should enable immune function in fish species, too small to provide sufficient blood for conventional immunological measures, to be assessed.
Role of bicarbonate ion in mediating decreased synaptic conductance in benzodiazepine tolerant hippocampal CA1 pyramidal neurons.

Abstract Chronic flurazepam treatment substantially impairs the function of GABAergic synapses on hippocampal CA1 pyramidal cells. Previous findings included a significant decrease in the synaptic and unitary conductance of CA1 pyramidal neuron GABAA receptor channels and the appearance of a GABAA-receptor mediated depolarizing potential. To investigate the ionic basis of the decreased conductance, whole-cell voltage-clamp techniques were used to record evoked, GABAA receptor-mediated IPSCs carried by HCO3−–Cl− or Cl− alone. Hippocampal slices were prepared from rats administered flurazepam orally for 1 week, 2 days after ending drug treatment. Slices were superfused with HCO3−–aCSF or with HEPES–aCSF (without HCO3−) plus 50 μM APV and 10 μM DNQX. The micropipette contained 130 mM CsCl and 1 μM QX-314. GABAA receptors located on pyramidal cell somata or dendrites were activated monosynaptically by maximal stimulation of GABAergic terminals at the stratum oriens–pyramidale (SO–SP) or stratum lacunosum–molecular (S-L–M) border, respectively. In HCO3−–aCSF, there was a significant reduction in synaptic-conductance in flurazepam-treated neurons following both SO–SP (control: 1058 pS, flurazepam: 226 pS, P 0.05; S-L–M: control 595 pS, flurazepam: 527 pS, P>0.05). Taken together, these findings suggest that a reduction in HCO3− flux may play a prominent role in mediating the action of GABA and that a loss of HCO3− conductance may significantly contribute to impaired GABAA receptor function after chronic benzodiazepine treatment.
Interaction of Arabidopsis DET1 with CCA1 and LHY in Mediating Transcriptional Repression in the Plant Circadian Clock

SUMMARY The COP10-DET1-DDB1 (CDD) complex is an evolutionarily conserved protein complex discovered for its role in the repression of photomorphogenesis in Arabidopsis. It is important in many cellular and developmental processes in both plants and animals, but its molecular mode of action remains poorly understood. Here, we show that the CDD component DET1 possesses transcriptional repression activity and physically interacts with two closely related MYB transcription factors, CCA1 and LHY, which are core components of the plant circadian clock. DET1 associates with the promoter of CCA1/ LHY target genes, such as TOC1, in a CCA1/LHYdependent manner and is required for their repression, suggesting a recruitment of DET1 by the central oscillator components to regulate the clock. Our results revealDET1as acore transcriptional repression factor important for clock progression. Overall, the CDD complex may function as a transcriptional corepressor in diverse processes through direct interaction with distinct transcription factors.
Deoxyhypusine Synthase Generates and Uses Bound NADH in a Transient Hydride Transfer Mechanism

Deoxyhypusine is a modified lysine residue. It is formed posttranslationally in the precursor of eukaryotic initiation factor 5A (eIF5A) by deoxyhypusine synthase, employing spermidine as a butylamine donor. In the initial step of this reaction, deoxyhypusine synthase catalyzes the production of NADH through dehydrogenation of spermidine. Fluorescence measurements of this reaction revealed a −22-nm blue shift in the emission peak of NADH and a ∼15-fold increase in peak intensity, characteristics of tightly bound NADH that were not seen by simply mixing NADH and enzyme. The fluorescent properties of the bound NADH can be ascribed to a hydrophobic environment and a rigidly held, open conformation of NADH, features in accord with the known crystal structure of the enzyme. Considerable fluorescence resonance energy transfer from tryptophan 327 in the active site to the dihydronicotinamide ring of NADH was seen. Upon addition of the eIF5A precursor, utilization of the enzyme-bound NADH for reduction of the eIF5A-imine intermediate to deoxyhypusine was reflected by a rapid decrease in the NADH fluorescence, indicating a transient hydride transfer mechanism as an integral part of the reaction. The number of NADH molecules bound approached four/enzyme tetramer; not all of the bound NADH was available for reduction of the eIF5A-imine intermediate.
Data-driven Distributionally Robust Polynomial Optimization

We consider robust optimization for polynomial optimization problems where the uncertainty set is a set of candidate probability density functions. This set is a ball around a density function estimated from data samples, i.e., it is data-driven and random. Polynomial optimization problems are inherently hard due to nonconvex objectives and constraints. However, we show that by employing polynomial and histogram density estimates, we can introduce robustness with respect to distributional uncertainty sets without making the problem harder. We show that the optimum to the distributionally robust problem is the limit of a sequence of tractable semidefinite programming relaxations. We also give finite-sample consistency guarantees for the data-driven uncertainty sets. Finally, we apply our model and solution method in a water network optimization problem.
Gustatory cross adaptation between sweet-tasting compounds

Taste profiles were obtained for 16 compounds after adaptation to sucrose, saccharin, and water. Sucrose adaptation reduced the sweetness of all sweet compounds. Saccharin adaptation, when analyzed over all compounds, also reduced sweetness, but the effect was less than that of sucrose. It is concluded that there may be a single receptor mechanism for the sweet quality. Adaptation to sucrose also increased the saltiness, sourness, and bitterness of the other compounds slightly. This increase should be attributed to the taste : induced in water by adaptation to sucrose rather than a potentiation of the other compounds per se.
Long‐term vegetation recovery on reclaimed coal surface mines in the eastern USA

Summary 1 While reclamation of degraded landscapes is becoming increasingly common, few studies have investigated the long-term effects of reclamation efforts on plant conservation. The goals of this study were to determine whether vegetation communities on reclaimed mines approximate those of the surrounding forest, and to evaluate how intensive reclamation practices used to address short-term erosion and water quality concerns affect long-term recovery. 2 In 1992–93 and 1999 the vegetation on 15 coal surface mines reclaimed between the years 1967–87, and five periodically logged hardwood forest reference sites in south-western Virginia, were surveyed. 3 Herbaceous species richness was similar on all sites, whereas woody species richness was higher in reference sites than in reclaimed sites. 4 Vegetation community composition on reclaimed sites continued to progress towards reference forest sites between the two sampling periods, but vegetation community composition even on the oldest sites (reclaimed > 35 years prior) still differed substantially from reference sites. 5 Herbaceous cover was higher and tree basal area was lower in reclaimed sites compared with reference sites at the first sampling period, but these differences were much less pronounced by the second sampling period. 6 The overall composition of the older reclaimed sites was similar to the reference forest sites, suggesting a high level of resilience in the forests studied. But, as with a number of previous studies of long-term recovery on highly disturbed sites, a number of less common forest species still had not colonized reclaimed sites, raising the question of their value for conservation. 7 These results concur with a common theme that goals for short-term and long-term recovery of highly disturbed sites may conflict. Planting with aggressive non-native ground cover species to minimize short-term erosion may have slowed long-term recovery on the sites studied. Widespread planting of Pinus strobus has not reduced species richness thus far, but may as the canopy closes. More emphasis should be given to long-term recovery potential in developing mine reclamation plans, and strategies to further this goal should be tested.
Gastro-oesofageale reflux bij zuigelingen

Bij gastro-oesofageale reflux is er terugvloed van maaginhoud in de slokdarm, met of zonder regurgitatie en spugen. Als dit asymptomatisch is, is er sprake van gastro-oesofageale reflux (GER). Van gastro-oesofageale refluxziekte (GERZ) wordt gesproken als het leidt tot hinderlijke klachten en/of complicaties bij de zuigeling, zoals prikkelbaar gedrag, voedselweigering, groeivertraging, het opgeven van bloedsliertjes, slaapproblemen, apparent life threatening episodes (ALTE), et cetera.1
Poly(methyl methacrylate) nanotubes in AAO templates: Designing nanotube thickness and characterizing the Tg-confinement effect by DSC

Abstract We used differential scanning calorimetry (DSC) to study the effect of confinement on the glass transition temperature (Tg) of poly(methyl methacrylate) (PMMA) nanotubes supported in anodic aluminum oxide (AAO) templates. We created nanotubes by wetting templates with polymer melts and developed a design equation relating tube thickness (ttube) with bulk radius of gyration (Rg): (ttube ≈ 2 Rg + 9 nm). The results indicate that ttube depends on overall conformation and size of the polymer coils and can be tuned at the nanoscale by polymer molecular weight. The Tg of AAO template-supported PMMA nanotubes increases with decreasing ttube, with Tg,tube − Tg,bulk = 12 K in 18-nm-thick nanotubes; we attribute the Tg increase to hydrogen bonds between PMMA ester side groups and hydroxyl groups on the surface of the γ-Al2O3 templates. Using ellipsometry, we characterized Tg-confinement effects for PMMA films supported on Si/SiOx, sputtered Al2O3 and sapphire (α-Al2O3). Films supported on substrates with higher concentrations of surface hydroxyl groups (α-Al2O3 > sputtered-Al2O3 > Si/SiOx) exhibit larger Tg-confinement effects. The DSC-determined Tg enhancements for nanotubes supported in γ-Al2O3 templates fall between the ellipsometry-determined Tg enhancements determined for PMMA films on α-Al2O3 and those for films on sputtered-Al2O3. These results show that molecular weight provides for tunability of polymer nanotube thickness in AAO templates, that there is excellent agreement in confinement effects measured by DSC and by ellipsometry, and that Tg can be tuned by modulating the levels of interfacial, polymer-substrate interactions by using surfaces with different chemical or crystallographic properties.
Aeration in the Laboratory

Publisher Summary It is noted that it is necessary to control aeration during microbiological experimentation,in order to measure aeration as accurately as possible and to report aeration procedures in quantitative terms, which permit their reproduction by other workers. For relatively uncomplicated procedures, equipment and analytical techniques are available to control aeration. Aeration is in many cases is a peripheral concern. At times, the objective is to produce spores, or antibiotics, or reproducible results in any of a multitude of experiments involving microbial growth. This chapter largely describes aeration procedure to the microbiologists who are not fermentation specialists. It demonstrates the need for controlling and measuring aeration in the laboratory. The chapter also summarizes the general principles involved in sound aeration practice and present practical guides for the application of these principles through commonly used equipment and techniques of measurement. Perfectly respectable aeration practices are well within the reach of any laboratory worker.
A Study of Organizational Reponses to Dilemmas in Interorganizational Emergency Management

Organizational scholars have traditionally used conceptual definitions to classify situational tensions such as dialectics, dilemmas, contradictions, and paradoxes. We propose instead to use organizational members’ reactions to define and distinguish among different forms of tensions. In the present study, we propose a model in which dilemmas vary in terms of press (the sense of urgency that they invoke) and balance (the degree to which both sides of the dilemma are regarded as equally important and urgent). Depending on the degree of press and balance, organizations are predicted to undertake various response strategies. To evaluate this model, we studied a large sample of members’ descriptions of organizational responses to dilemmas in the Dutch crisis response system (N = 149). Results indicated variation in press and balance, and while some participants enacted dilemmas as choices, others enacted dilemmas in ways that acknowledged and tried to address both alternatives.
Suppression of atomic radiation in a cylindrical nanocavity

An excited atom placed inside a cylindrical nanocavity cannot radiate if the frequency of emission is below the cutoff frequency for electromagnetic wave propagation in the cavity. However, we demonstrate that it can be de-excited through the emission of surface plasmons. The observable effect will be a substantial enhancement in the lifetime of dipole-allowed transitions. The recently discovered carbon nanotubules will be explored as potential nanometer scale cylindrical cavities and the lifetimes of excited states of Helium (2p → 1s) in the earbon nanocavities will be calculated as an example of this nonradiative decay mechanism. The dependence of the transition rate as a function of the radial distance from the tube surface is studied by varying the initial radial quantum number of the center-of-mass wavefunction for an atom confined within the nanotube. The results of the calculation are used to explore the possible application of concentric carbon nanotube structures as TEM waveguides.
Portable microfluidic raman system for rapid, label-free early disease signature detection

In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.