cssi/SciSciGPT-SciSciNet huggingface dataset:
Differences in the amino acid distributions of 310‐helices and α‐helices

Local determinants of 3(10)-helix stabilization have been ascertained from the analysis of the crystal structure data base. We have clustered all 5-length substructures from 51 nonhomologous proteins into classes based on the conformational similarity of their backbone dihedral angles. Several clusters, derived from 3(10)-helices and multiple-turn conformations, had strong amino acid sequence patterns not evident among alpha-helices. Aspartate occurred over twice as frequently in the N-cap position of 3(10)-helices as in the N-cap position of alpha-helices. Unlike alpha-helices, 3(10)-helices had few C-termini ending in a left-handed alpha conformation; most 3(10) C-caps adopted an extended conformation. Differences in the distribution of hydrophobic residues among 3(10)- and alpha-helices were also apparent, producing amphipathic 3(10)-helices. Local interactions that stabilize 3(10)-helices can be inferred both from the strong amino acid preferences found for these short helices, as well as from the existence of substructures in which tertiary interactions replace consensus local interactions. Because the folding and unfolding of alpha-helices have been postulated to proceed through reverse-turn and 3(10)-helix intermediates, sequence differences between 3(10)- and alpha-helices can also lend insight into factors influencing alpha-helix initiation and propagation.
Spatiotemporal evolution of a transient slip event on the San Andreas fault near Parkfield, California

[1] In 1993 several baselines of the two-color electronic distance meter (EDM) network at Parkfield, California, deviated from their long-term rates, coincident with anomalous observations from nearby strain meters and a creep meter, as well as an increase in microseismicity. Between October 1992 and December 1994, three M ∼ 4.5 earthquakes occurred beneath Middle Mountain, near the hypocenter of the 1934 and 1966 Parkfield M6 events. We analyzed the two-color EDM data using a Kalman-filtering based technique to image the spatiotemporal evolution of slip on the fault at Parkfield between the mid-1980s and 2003. This method accounts for localized random walk motion of the geodetic monuments and a prominent seasonal signal that affects many baselines. We find that a slip rate increase occurred between January 1993 and July 1996 on the upper 8 km of the fault near Middle Mountain. The peak estimated slip rate during this time was 49 mm/yr, which exceeds the long-term geologic rate of ∼35 mm/yr. The slip rate evolution appears episodic, with an initial modest increase after the M4.3 earthquake and a much larger jump following the shallower M4.7 event in December 1994. This temporal correlation between inferred slip and seismicity suggests that the moderate earthquakes triggered the aseismic fault slip. The EDM data cannot resolve whether transient slip propagated across the nucleation zone of the 1934 and 1966 M6 Parkfield earthquakes. However, transient slip and its associated stress release in the hypocentral area of previous Parkfield events is consistent with the nucleation of the 2004 M6 Parkfield earthquake elsewhere on the fault.
Depth regulatory behavior of the first stage zoea larvae of the sand crab Emerita analoga Stimpson (Decapoda: Hippidae)

Abstract Laboratory studies of the behavior of first stage zoea larvae of the sand crab Emerita analoga Stimpson have shown that while newly-hatched larvae are strongly photopositive, this response lasts only about four hours, as the larvae rapidly become photonegative. After becoming photonegative, a large proportion of the larvae remain so throughout the first four days of life if they are fed Artemia nauplii; if starved, the larvae become significantly more photopositive than when fed. Both the photopositive response of newly-hatched larvae and the reversal to photopositive behavior in response to starvation are only apparent under horizontal test conditions. Increases in hydrostatic pressure stimulate swimming activity among the larvae; responsiveness to pressure being greatest at hatching and decreasing thereafter. The pressure response is strongly oriented to light; pressure-stimulated larvae will swim towards a light source regardless of whether this involves upward, downward, or horizontal motion. Experiments suggest that the pressure response provides the primary mechanism for depth regulation among young larvae; gravity and light may augment the pressure ‘sense’ by serving as primary orientational cues. The nutritional status of an individual larva may alter its depth-regulatory capabilities, but this effect is not yet clear.
A hemoprotein from azotobacter containing non-heme iron: Isolation and crystallization

Abstract A new type of hemoprotein was isolated from extracts of Azotobacter vinelandii using a heat step, application of the protamine-cellulose phosphate procedure, and precipitation with MgCl2. Crystallization was achieved using low concentration of MgCl2. The protein was shown to be a unique cytochrome of the b type containing up to 20% non-heme iron but no “acid labile sulfur”. Both the heme and non-heme iron appear to be functional redox components.
Bilateral Pseudocyst of the Auricle in an Infant Girl

A 6-week-old girl developed bilateral auricular swelling in the absence of trauma. Clinical and histologic findings were consistent with pseudocyst of the auricle. This case is unusual given the age and sex of the patient and the bilateral presentation of the pseudocysts.
Prescribed burning effects on upland Quercus forest structure and function

The effects of prescribed burning, herbicide application, and thinning treatments were examined in upland Quercus stands with a replicate block field study. Two site types were analyzed: (1) nonsuccessional with a Quercus overstory and Quercus understory, and (2) successional with a Quercus overstory and an Acer saccharum understory. Treatments were examined for their effects on vegetation structure and composition, especially with respect to altering the natural succession from Quercus communities to mesophytic species. In addition, impacts of burning on soil nutrients were examined prior to and immediately following burn treatments. Results from the study indicate that fire had little effect on A horizon soil nutrients following burns. The data suggest fire plays a more important role as a decomposer for nutrient release in February burns than in November burns. Natural precipitation and leaching from the litter layer in the fall rendered similar nutrient dynamics as burning in November. The structural changes to vegetation following fire were more noticeable than compositional changes. Thinning of the canopy was generally necessary for the understory to respond to burning treatments. Burning did not affect stems >3.8 cm dbh (diameter at breast height). Density of most woody species <3.8 cm dbh decreased with burning, but increased with burning and thinning, indicating the stress of shaded conditions. Thus, burning prior to thinning may be an effective method for controlling an A. saccharum invasion into Quercus stands. Herbaceous, seedling, sapling, and overstory strata diversity were unaffected by the treatments. Data indicated that the community responds with species extant at the time of treatment. Thus, the initial conditions prior to disturbance were important factors in the response of the stand to disturbance. Although fire has played a major role in upland forest dynamics prior to settlement, forest structure and composition can no longer be maintained by fire. Succession without fire has resulted in a different structure and composition to oak forests, altering both fuels and fuel moisture levels. Species normally considered intolerant of fire have reached size classes large enough that they tolerate cool to moderate burns. More severe disturbance techniques, or combinations of techniques, are necessary for sustainable oak forest management in the central hardwood region. # 2003 Elsevier Science B.V. All rights reserved.
Prediction-preserving reducibility

We investigate a model of polynomial-time concept prediction which is a relaxation of the distribution-independent model of concept learning due to Valiant. Prediction-preserving reductions are defined and are shown to be effective tools for comparing the relative difficulty of solving various prediction problems. A number of prediction-preserving reductions are given. For example, if deterministic finite automata are polynomially predictable, then so are all Boolean formulas. We develop a complexity theory for prediction problems that parallels standard complexity theory. It is shown that certain problems of concept prediction are “prediction-complete” for a complexity class—a polynomial time algorithm for the prediction problem would imply that all languages in the complexity class are polynomially predictable. For example, polynomial-time prediction of deterministic finite automata implies the polynomial predictability of all languages in the class LOG (deterministic logspace). Similar natural prediction-complete problems are given for the standard complexity classes NC1, NLOG, LOGCFL, and P. Showing that a prediction problem is prediction-complete for any of these classes provides varying degrees of evidence that no efficient prediction algorithm exists for the problem. Based on very weak cryptographic assumptions, we establish hardness results for prediction of Boolean circuits and other prediction problems that are prediction-complete for P. The recent related resuts of Kearns and Valiant are discussed, which show that Boolean formulas and DFAs are not polynomially predictable based on the assumed intractability of computing specific cryptographic functions.
The PDAF based active contour

We present a new active contour model in spatio-velocity space which is based on the probability data association filter (PDAF) approach. It employs a directional-based measurement model of image potential and of optical-flow along the contour points. The proposed directional approach of measurements is the basis for the velocity-based discrimination between measurements of the object to that of image clutter. The model chooses the appropriate measurements which are most consistent with previous estimation of motion in the sense of the PDAF approach. In order to obtain reliable measurements of image motion and of gradient-based image potential, we propose a directional smoothing operator which is the basis for discriminating the objects measurements from that of image clutter. The method was applied to real world tracking problems such as a walking leg and a waving hand.
Building Trust and Satisfaction in Travel Counselor/Client Relationships

Abstract In today's business environment, travel counselors are challenged to do everything that they can to hold onto their valued customers. We report the results of a study designed to examine the factors that are related to client trust and satisfaction with travel counselors. One hundred and eighty-one business travelers were surveyed about their relationships with their travel agent. The results indicate that travel counselor dependability, expertise, familiarity, and company reputation lead to greater client trust; while dependability, familiarity, and civility predict client satisfaction. Based on these results and prior research on customer trust, recommendations are made for enhancing client relationships.
RUSLE Model Description and Database Sensitivity

Water quality modeling generally requires estimates of the amount of eroded material entering water courses. This information is necessary because sediment often transports adsorbed chemicals. Numerous models have been developed to assist with assessment of this problem. These models often contain some modification of the Universal Soil Loss Equation (USLE). A recently initiated effort to improve USLE technology has produced a computer-based model, RUSLE (Revised USLE), which employs new relationships to estimate values of the six factors in the equation. Three input databases are required: climatic data, crop data, and field operations data. Although numerous specific entries for these data are contained in the program, in many cases users must supplement or modify the supplied data [...]
Clever clustering vs. simple speed-up for summarizing rushes

This paper discusses in detail our approaches for producing the submitted summaries to TRECVID, including the two baseline methods. The cluster method performed well in terms of coverage, and adequately in terms of user satisfaction, but did take longer to review. We conducted additional evaluations using the same TRECVID assessment interface to judge 2 additional methods for summary generation: 25x (simple speed-up by 25 times), and pz (emphasizing pans and zooms). Human assessors show significant differences between the cluster, pz, and 25x approaches. The best coverage (text inclusion performance) is obtained by 25x, but at the expense of taking the most time to evaluate and perceived as the most redundant. Method pz was easier to use than cluster and had better performance on pan/zoom recall tasks, leading into discussions on how summaries can be improved with more knowledge of the anticipated users and tasks.
Modeling and simulation of auction-based shop-floor control using parallel computing

The high level of complexity and cost involved in the development, testing, and implementation of software for traditional, hierarchical shop-floor control of automated manufacturing systems has motivated considerable research in recent years on the distributed shop-floor control paradigm. In this paper, we describe a methodology for modeling and simulation of an auction-based shop-floor control scheme in a parallel and distributed computing environment using the Parallel Virtual Machine software library. Compared to traditional discrete-event simulation, this approach provides a more accurate means for modeling and evaluation of the shop-floor behavior under distributed control, and enables rapid prototyping of the actual control software. We discuss the challenges and highlight research opportunities associated with modeling and simulation of distributed shop-floor control systems using parallel and distributed computing.
Some aspects of modelling low-level jets

An improved non-stationary two-layer model is presented for the simulation of wind speed maxima in the nocturnal boundary layer. The model is based on the idea of Blackadar (1957), who proposed as forcing mechanism an inertial oscillation of the ageostrophic component of the wind vector in the levels above the top of the nocturnal radiation inversion. First, the time-dependent variation of the nocturnal boundary-layer height is studied by means of prognostic equations; there is a good agreement between observed and calculated height data for three days of the Wangara experiment. Furthermore, a diurnal variation of the drag coefficient is considered in the lower layer by decreasing the coefficient by a factor of 10–20 due to stabilization of this layer during the night. The marked temporal decrease (increase) of the drag coefficient in the first hours after sunset (sunrise) is described by a function $$C_{D(t)} = C_{DN} - A\sqrt[4]{{\sin ({\pi \mathord{\left/ {\vphantom {\pi {2T}}} \right. \kern-\nulldelimiterspace} {2T}})t}}$$ . The incorporation of these two effects into the model gives results which are in good agreement with observed wind data for Wangara days 13/14, 30/31, and 33/34.
Subcommunity Change in a Changing Metropolis

Residential areas in cities and suburbs change as they age. The conventional concepts that represent this process are succession and the neighborhood life cycle. In this study we use cohort analysi...
Automatic light-source placement for detecting object features

The selection and placement of cameras and light sources for a specific task (e.g., locating a part in a tray or inspecting an object) is one of the most important steps in creating a successful vision system, because obtaining high-quality images can greatly simplify the vision algorithms and improve their reliability. We will describe techniques that use a visual task description stated in terms of features to be detected, and derive a range of light-source locations that satisfy the task requirements. In particular, given a task description that specifies particular object edges to be detected with a given edge detector (e.g., a Sobel edge operator), our techniques determine the constraints on light-source location such that the edge is detected.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Whole body irradiation combined with adoptive T cell transfer results in regression of high-grade intraepithelial neoplasia and long-term persistence of tumor-specific CD8+ T cells in TRAMP mice

Lymphodepleting whole body irradiation (WBI) can enhance adoptive T cell transfer-mediated tumor regression in a variety of experimental models and a subset of patients. We investigated the potential of this approach to impact established prostate cancer using the clinically relevant and immunosuppressive TRAMP model of prostatic adenocarcinoma. 18-week-old TRAMP mice bearing high-grade prostatic intraepithelial neoplasia (PIN) were treated with 475cGy WBI followed by adoptive transfer of naive T cell receptor transgenic CD8+ T cells (TCR-IV) specific for the Site IV determinant in SV40 T-antigen. TCR-IV cells proliferated in both irradiated and non-irradiated TRAMP mice, but accumulated to significantly higher levels and persisted for 21 days in irradiated mice. Neither treatment group developed a population of IFNγ-producing TCR-IV cells in the prostate, but a significantly larger number of Granzyme B-producing cells infiltrated the prostates of mice conditioned with WBI. The addition of WBI also delayed the onset of tolerance, as the TCR-IV cells in irradiated mice remained responsive to immunization. WBI alone and WBI with adoptive transfer tended to reduce the size of the urogenital tract and reduce the incidence of adenocarcinoma at 28 weeks of age, but no regressions were observed. However, a subset of TRAMP mice treated with two rounds of WBI-enhanced adoptive immunotherapy exhibited only low- or moderate-grade PIN at 28 weeks of age, indicative of tumor regression. The remainder of mice in this group exhibited no disease progression beyond high-grade PIN, and all mice in the group maintained a detectable population of TCR-IV cells 49 days after the second adoptive transfer. In contrast, at least a subset of mice in remaining groups progressed to adenocarcinoma, and all lacked detectable TCR-IV cells. These results demonstrate that WBI conditioning extends the persistence of effector phenotype tumor-specific T cells in the highly tolerogenic microenvironment of the tumor-bearing TRAMP prostate, and suggest that multiple rounds of therapy can promote regression of established prostate lesions.
Monoclonal antibody ST1 identifies an antigen that is abundant in the axolotl and newt limb stump but is absent from the undifferentiated regenerate

Monoclonal antibodies (mAb) utilized in regeneration studies to date identify antigens that are up-regulated in the blastema. We obtained a monoclonal antibody, designated ST1 (Stump 1), that is reactive to an extracellular matrix (ECM) antigen exhibiting the opposite distribution; ST1 is an abundant antigen of the limb stump soft tissues but is absent from within the blastema. The border between abundance and absence of mAb ST1 reactivity was sharp and extended as a concavity into the stump. This distinct dichotomy led to further studies relevant to understanding how this extracellular matrix antigen is modulated during regeneration. mAb ST1 reactivity decreased in the internal tissues at the distal end of the limb prior to blastema formation and remained absent until the onset of differentiation. The initial decrease in mAb ST1 reactivity was dependent on the combined effects of injury and the wound epithelium but was nerve independent. At blastema stages of regeneration, the distribution of tenascin, ascertained by mAb MT1 reactivity, closely matched the area without reactivity to mAb ST1. The spatial and temporal distribution of the ST1 antigen in unamputated limbs and during regeneration did not correspond to any previously described ECM component.
Reduction of chlorodiadamantylmethane by single electron transfer

Abstract Chlorodiadamantylmethane is shown to react with tert -butyllithium to give diadamantylmethane through a mechanism involving single electron transfer.
Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study.

Platelet adhesion, activation, and aggregation are central to thrombus formation, which follows atherosclerotic plaque disruption and causes acute coronary syndromes. Aspirin and clopidogrel exert their antiplatelet effects by inhibiting thromboxane A2 production and adenosine diphosphate–induced platelet aggregation pathways, respectively. Aspirin has proven benefits in primary and secondary prevention of coronary artery disease. Clopidogrel, an alternative antiplatelet agent used in patients with aspirin intolerance, is especially useful in combination with aspirin after coronary stent procedures. The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study demonstrates for the first time the benefit of adding clopidogrel to aspirin rather than using aspirin alone in patients having acute coronary syndromes without ST-segment elevation myocardial infarction. Patients who are resistant to aspirin (up to 10%) have higher rates of cardiovascular events and may derive special benefit from the combination therapy. Aspirin resistance can be assessed through platelet aggregometry testing, measurement of urinary thromboxane metabolites, and, possibly, genomic testing in the future. Arch Intern Med. 2003;163:1145-1153 The CURE 1 (Clopidogrel in Unstable AnginatoPreventRecurrentEvents)studyprovides evidence for the usefulness of clopidogrel in patients having acute coronary syndrome (ACS) without ST-segment elevation. The major finding of the study is that clopidogrel given in conjunction with aspirin improves the outcome of patients with ACS compared with aspirin treatmentalone.Clopidogrelappearstoaddincremental value to conventional therapy. The purpose of this review is to critically analyze the findings of several antiplatelet trials with a focus on the CURE study, and toprovideguidanceintheuseofaspirinand clopidogrel for patients with ACS.
The unified acoustic and aerodynamic prediction theory of advanced propellers in the time domain

This paper presents some numerical results for the noise of an advanced supersonic propeller based on a formulation published last year. This formulation was derived to overcome some of the practical numerical difficulties associated with other acoustic formulations. The approach is based on the Ffowcs Williams-Hawkings equation and time domain analysis is used. To illustrate the method of solution, a model problem in three dimensions and based on the Laplace equation is solved. A brief sketch of derivation of the acoustic formula is then given. Another model problem is used to verify validity of the acoustic formulation. A recent singular integral equation for aerodynamic applications derived from the acoustic formula is also presented here.
Structural Requirements for the Enzymatic Deamination of Cytosine Nucleosides

Thirty-three 1-β-D-pentofuranosylcytosine nucleosides were examined as substrates of crude cytidine deaminase from mouse kidney. In addition to previous observations of structural features in substrates required for enzymatic deamination [e.g., a free 3′-hydroxyl in the ‘down’ ribo (arabino)configuration] we find that: modification of the aglycon by substitution of a fluorine atom at C(5) results in a several-fold increase in the deamination velocity relative to cytidine whereas insertion of a methyl group at C(5) decreases the deamination velocity. This decrease is even more pronounced when a methyl group is substituted at C(6). Though xylosylcytosine and 3′-deoxy-3′-fluoro-xylo-C are not substrates for this deaminase, those xylofuranosylcytosines bearing good leaving groups (e.g., bromo, mesyloxy, or tosyloxy) at C(3′) are deaminated with substantial deamination velocities. This is probably due to a prior chemical reaction leading to arabino nucleosides bearing a free ‘down’ 3′-hydroxyl. A different situation is obtained with arabino nucleosides. Though ara-C and 2′-deoxy-2′-fluoro-ara-C are substrates for this deaminase, substitution of bulky groups (e.g., chloro, bromo, or mesyloxy) at C(2′) substantially decreases the susceptibility to deamination. An hypothesis is offered to explain these differences between xylo-and arabino-cytosines. The presence of a free hydroxyl group at position 5′ is not essential for enzymatic deamination.
Synthesis and Studies on the Effect of 2-Thiouridine and 4-Thiouridine on Sugar Conformation and RNA Duplex Stability

In order to understand the effect of 2-thiouridine (s2U) substitution on RNA structure and the potential for stabilization of tRNA codon-anticodon interactions through s2U-34 modification, a pentamer RNA sequence, Gs2UUUC, was synthesized and characterized by NMR spectroscopy. The single strand contains the UUU anticodon sequence of tRNALys with flanking GCs to increase duplex stability. Regiochemical effects of uridine thiolation were determined by comparing the structure and stability of the 2-thiouridine containing oligonucleotide with an identical sequence containing 4-thiouridine (s4U) and also the normal uridine nucleoside. Circular dichroism spectrum indicated an A-form helical conformation for Gs2UUUC which was further confirmed by 2D ROESY NMR experiments. The duplex stability of the three pentamers complexed with a 2'-O-methyl-ribonucleotide complementary strand, GmAmAmAmCm, was determined by UV thermal melting studies and by 1H NMR spectroscopy. The duplex containing s2U has a T m of 30.7 degrees C compared to 19. 0 degrees C for the unmodified control and 14.5 degrees C for the s4U containing duplex. The results from UV experiments were corroborated by imino proton NMR studies that show proton exchange rates, chemical shift differences, and NH proton linewidths indicative of the stability order s2U >U >s4U. The magnitude of the effect of s2U in our model system is comparable to the 20 degrees C stabilization observed by Grosjean and co-workers for 2-thiolation in a codon-anticodon model system composed of two tRNAs with complementary anticodon sequences [Houssier, C., Degee, P., Nicoghosian, K. and Grosjean, H. (1988) J. Biomol. Struct. Dyn., 5, 1259-1266].
Some effects of antidromic stimulation of frog retinal ganglion cells

Abstract Electrical stimulation of the frog optic nerve produced orthodromic discharges following antidromic invasion of certain retinal ganglion cells, under conditioning which tended to minimize cellular damage. The range of latencies from optic nerve stimulus for the orthodromic spikes was 11–72 msec. Light inhibited these orthodromic discharges without affecting the antidromic invasion. If antidromic stimulation were applied more rapidly than 3/sec the orthodromic discharge did not occur, while the cell could follow antidromic stimulation up to 50/sec. In addition, tetanic stimulation failed to produce reliable changes in the response of ganglion cells to illumination.
On Orientation Changes Accompanying Slip and Twinning

The purpose of this note is to make a few observations on several analyses of lattice rotation by slip and by twinning in deformation.
A Multi-dimensional Component Importance Analysis Mechanism for Component Based Systems

In a component-based system, both the reliability and topological location of each component contribute to the software architecture reliability. Due to the limited resources, it is very crucial to identify the key set of components such that we will be able to devote our resources to those components in order to improve the system availability and reliability most effectively. Unfortunately, few works have been dedicated to the analysis of component importance and the system reliability from the aspect of components' location. This paper introduces a multi-dimensional mechanism to analyse the importance of components in a system and the their influences on the reliability from four aspects: centrality, entropy, costumer preference and service priority. This mechanism provides an interactive approach to identify the key set of components during the architecture design phase. Both centrality and entropy evaluate the component influence from static perspective. On the other hand, we estimate component importance from the dynamic point of view with costumer preference and service priority during application execution.
Dissolved Organic Carbon Losses from Tile Drained Agroecosystems

Artificial subsurface drainage is commonly used in midwestern agriculture and drainage losses of dissolved organic carbon (DOC) from such systems are an under-quantified portion of the terrestrial carbon (C) cycle. The objectives of this study were to determine the effect of common agricultural management practices on DOC losses from subsurface tile drains and to assess patterns of loss as a function of year, time of year, and drainflow. Daily drainflow was collected across six water years (1999-2004) from a restored prairie grass system and cropping systems which include continuous corn (Zea mays L.) and corn-soybean [Glycine max (L.) Merr.] rotations fertilized with urea-ammonium-nitrate (UAN) or swine (Sus scrofa) manure lagoon effluent. The DOC concentrations in tile drainflow were low, typically <2 mg L -1 . Yearly DOC losses, which ranged from 1.78 to 8.61 kg ha -1 , were not affected by management practices and were small compared to organic C inputs. Spring application of lagoon effluent increased yearly flow-weighted (FW)-DOC concentrations relative to other cropping systems in three of the years and increased monthly FW-DOC concentrations when drainflow occurred within 1 mo of application. Drainflow was significantly and positively correlated with DOC loss. Drainflow also affected DOC concentrations as greater 6-yr cumulative drainflow was associated with lower 6-yr FW-DOC concentrations and greater daily drainflow was associated with higher daily DOC concentrations. Our results indicate that lagoon effluent application and fertilizer N rates do not affect long-term losses of DOC from tile drains and that drainflow is the main driver of DOC losses.
Bifunctional Ligands that Target Cells Displaying the αvβ3 Integrin

Strategies to eliminate tumor cells have long been sought. We envisioned that a small molecule could be used to decorate the offending cells with immunogenic carbohydrates and evoke an immune response. To this end, we describe the synthesis of bifunctional ligands possessing two functional motifs: one binds a cell-surface protein and the other binds a naturally occurring human antibody. Our conjugates combine an RGD-based peptidomimetic, to target cells displaying the alpha v beta3 integrin, with the carbohydrate antigen galactosyl-alpha(1-3)galactose [Galalpha(1-3)Gal or alpha-Gal]. To generate such bifunctional ligands, we designed and synthesized RGD mimetics 1 b and 2 c, which possess a free amino group for modification. These compounds were used to generate bifunctional derivatives 1 c and 2 d, with dimethyl squarate serving as the linchpin; thus, our synthetic approach is modular. To evaluate the binding of our peptidomimetics to the target alpha v beta3-displaying cells, we implemented a cell-adhesion assay. Results from this assay indicate that the designed, small-molecule ligands inhibit alpha v beta3-dependent cell adhesion. Additionally, our most effective bifunctional ligand exhibits a high degree of selectivity (4000-fold) for alpha v beta3 over the related alpha v beta5 integrin, a result that augurs its utility in specific cell targeting. Finally, we demonstrate that the bifunctional ligands can bind to alpha v beta3-positive cells and recruit human anti-Gal antibodies. These results indicate that both the integrin-binding and the anti-Gal-binding moieties can act simultaneously. Bifunctional conjugates of this type can facilitate the development of new methods for targeting cancer cells by exploiting endogenous antibodies. We anticipate that our modifiable alpha v beta3-binding ligands will be valuable in a variety of applications, including drug delivery and tumor targeting.
Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy

After refraining from smoking for at least 8 hours, 22 adult male habitual smokers underwent baseline electrophysiologic study including atrial and ventricular burst pacing and programmed premature stimulation with single extrastimuli. After smoking 2 of their usual brand of cigarettes in rapid succession, the electrophysiologic protocol was repeated. Nicotine, catecholamine and carbon monoxide concentrations all increased significantly. Smoking increased heart rate and improved atrioventricular conduction in the 13 patients receiving chronic beta-blocker therapy (mostly for angina pectoris); increases in heart rate and improvement in atrioventricular conduction were not different statistically from those seen in patients not receiving beta-blocker therapy, suggesting the possibility of a direct effect of nicotine or other components of tobacco smoke. Ventricular refractoriness was not altered and atrial and ventricular arrhythmias were not increased by smoking. Persistent sympathomimetic actions of cigarette smoking may explain in part the failure of beta-blocking drugs to reduce cardiac mortality risk in smokers after myocardial infarction.
Prostaglandin F2α (PGF2α) and prolactin secretion in rats

Plasma prolactin and F-prostaglandins (PGF) were measured anesthetized male Sprague-Dawley rats before and at 15, 30, 45 and 60 minutes following i.v. injection of either PGF2alpha (4 mg/kg), chlorpromazine, 1 mg/kg or chlorpormazine (1 mg/kg) after pretreatment with i.p. indomethacin (2 mg/kg). Following PGF2alpha administration, plasma prolactin levels increased significantly only at 15 and 30 minutes in spite of extremely high PGF levels throughout 60 minutes. Besides the expected rise in plasma prolactin, chlorpromazine caused a transient but statistically significant increase in PGF. Indomethacin blocked the chlorpormazine-induced PGF rise but not prolactin increase. Animals stressed with ether anesthesia showed elevation of plasma prolactin, which was not blocked by indomethacin although PGF concentration fell. Theese results indicate that PGF2alpha can stimulate prolactin release. This effect does not appear to be physiologic since very high PGF levels are required. Furthermore, blockade of prostaglandin synthesis by indomethacin does not prevent the release of prolactin in response to chlorpormazine or stress. Our findings do not support a possible role of PGFs as intermediaries in prolactin release. However, it is possible that PGFs may work through other mechanisms not investigated in our study.
LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models

The HGF/MET signaling pathway regulates a wide variety of normal cellular functions that can be subverted to support neoplasia, including cell proliferation, survival, apoptosis, scattering and motility, invasion, and angiogenesis. MET over-expression (with or without gene amplification), aberrant autocrine or paracrine ligand production, and missense MET mutations are mechanisms that lead to activation of the MET pathway in tumors and are associated with poor prognostic outcome. We report here preclinical development of a potent, orally bioavailable, small-molecule inhibitor LY2801653 targeting MET kinase. LY2801653 is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min−1 and t1/2 of 525 min. LY2801653 demonstrated in vitro effects on MET pathway-dependent cell scattering and cell proliferation; in vivo anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects. LY2801653 also maintained potency against 13 MET variants, each bearing a single-point mutation. In subsequent nonclinical characterization, LY2801653 was found to have potent activity against several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2 and against the serine/threonine kinases MKNK1/2. The potential value of MET and other inhibited targets within a number of malignancies (such as colon, bile ducts, and lung) is discussed. LY2801653 is currently in phase 1 clinical testing in patients with advanced cancer (trial I3O-MC-JSBA, NCT01285037).
Reversible decrease in dopaminergic 3H-agonist binding after 6-hydroxydopamine and irreversible decrease after kainic acid.

Abstract Six days after the unilateral intrastriatal injection of 30 ug 6-hydroxydopamine (6-OHDA) the number of stereospecific 3H-dopamine and 3H-apomorphine binding sites (Bmax) was reduced by 50–60% in the caudate nucleus ipsilateral to the lesion. The dopamine content of the lesioned caudate nucleus was also reduced to 2% of the contralateral side or of sham-operated controls. The preincubation of depleted homogenates with added dopamine reversed the effects of 6-OHDA on the Bmax of 3H-agonists. A similar pattern of depletion, decrease in binding and in vitro reversal by dopamine was observed after a single injection of reserpine (4.0 mg/kg, im.). The intrastriatal injection of kainic acid also lowered the Bmax of 3H-agonists by 65% without altering dopamine content. Preincubation of homogenates of kainic acid-lesioned caudate nuclei with 355 nM (endogenous) dopamine did not reverse the decrease in binding. We conclude that treatments which deplete endogenous dopamine, including the lesion of nigrostriatal terminals, induce a reversible change in the parameters of 3H-agonist binding whereas the destruction of intrinsic caudate neurons with kainic acid results in an irreversible loss of receptors.
Effect of furosemide upon endolymph potassium concentration

Abstract Chinchillas were anesthetized with ketamine (40 mg/kg i.m.) and endocochlear potential (EP) and potassium concentration in endolymph (Ke + ) were determined in control animals and in animals injected with various doses of furosemide (25, 50 or 100 mg/kg i.v.) by means of microelectrodes inserted into scala media. Control EP and Ke + in the chinchilla were 81.3±3.8 mV and 158.5±3.2 mequiv ./1, respectively. Following injection of furosemide, a dose-related fall in EP and Ke + was observed. However, the EP declined much more rapidly than the Ke + , and recovered more quickly than the latter. The recovery of Ke + tended to lag behind the EP recovery. The debate over whether potassium transport into endolymph and endocochlear potential generation are related or independent events is discussed in the light of recent literature and the present study.
A utility-based analysis of the wage subsidy program

Abstract Because the poverty line is usually defined in terms of income, two families may be classified as having poverty-level incomes even though their hours of work and, therefore, their utilities may be very different. This paper compares a government income support program that defines the poverty line in terms of utility with several other support programs that define the poverty line in terms of income. Through the use of the wage solution of the indirect utility function, we find the amount of wage subsidy required to raise a subpoverty-line family to the poverty line as defined by the utility function. This subsidy is compared with wage subsidies based on directly observable quantities such as income.
FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder

Abstract In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [ 18 F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale–Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group ( F =6.07, d.f.=1,17, P =0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (τ=0.35, P =0.04), but worse outcome (τ=−0.57, P =0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.
Dudresnaya babbittiana (Dumontiaceae, Gigartinales), a new red algal species from Midway Atoll, North Central Pacific

Abstract Dudresnaya babbittiana I.A. Abbott et McDermid, sp. nov., is described from subtidal habitats at Midway Atoll, among the westernmost reefs and lagoons and series of islets in the Hawaiian archipelago. The new species differs in size, habit, internal rhizoids and auxiliary-cell morphology from the two species that have been previously described from the high islands of Hawaii about 1 400 km to the southeast, D. hawaiiensis R.K.S. Lee and D. littleri I.A. Abbott. Closest affinities appear to be with D. capricornica Robins et Kraft from tropical eastern and western Australia, which differs in having a much greater abundance of medullary rhizoids, more consistently present and larger hexagonal crystals in central-axial cells, a far less regular alignment of surface cortical cells, and differently structured carpogonial and auxiliary-cell filaments.
The Effect Of Suspensoids On Optical Parameters In A Typical Estuary

AbstractAs a first step in optical modeling of coastal areas the effects of various suspen-soids on optical parameters were studied in the Patuxent River, a subestuary of Chesapeake Bay. Particle populations were measured using a Coulter Counter, while both inherent andapparent optical properties were being monitored. Results are presented indicating strongrelationships between beam attenuance and total suspensoids, including both suspendedsediments (particle diameters between 1 and 5 x10-6m) and phytoplankton (particle diame-ters between 15 and 35 x10-6m). Relationships of natural phenomena such as tidal currentsand daylight period with sediment and plankton populations are also demonstrated. As expected, efforts at predicting inherent optical properties from apparent, and vice versa,were not too successful.From these studies it appears possible to develop models capable of predicting,within reasonable limits, optical properties of coastal waters when local conditions suchas weather, input stream characteristics, and local topographic conditions are known.IntroductionAs a result of attempts to apply new technology to the measurement of depth, theDefense Mapping Agency has found itself very deeply involved with the optical propertiesof coastal waters. This is due to the fact that the two new bathymetry systems seeming tohave the most promise are those that use remote sensing multispectral scanners and lasers;both of which are dependent on sea water optical properties. In order to model theenvironment for optimal use of these devices, especially to determine the degradation ofthe environment as a result of various natural phenomena such as weather events, it isnecessary to specify the environmental conditions that control the optical parameters ofinterest. This paper attempts to describe some initial measurements which hopefully willaid in future modeling efforts.We can relate the distribution of algae and suspended solids to easily obtainableparameters such as wind, tide, season, and temperature; and if we can further relate algaland sediment concentrations to optical properties of the environment, modeling effortsshould be greatly simplified.MethodologyOur study was centered in the Patuxent River, a small subestuary of the Chesapeake
Lung morphogenesis revisited: old facts, current ideas.

Classical studies using epithelial-mesenchymal recombinants have identified basic rules of how tissue interactions regulate patterning of developing branching structures such as the lung. Nevertheless, only recently, molecular mediators of these interactions have been identified. Formation of bronchi or pre-alveolar structures seems to depend on the activity of distinct gene networks along the proximal-distal axis of the respiratory tract. Recent studies reveal that these networks and the mechanisms that they regulate can be conserved among species and comprise a variety of soluble and transcription factors also found in other developing organs. Here, current data and ideas about how these factors act regulating lung development will be reviewed. © 2000 Wiley-Liss, Inc.
1078 FACTORS ASSOCIATED WITH ELEVATED SERUM CONCENTRATIONS OF CHLORAMPHENICOL (CAP) IN CHILDREN

Recently the recommended pediatric dosage for IV chloramphenicol has been lowered from 100 mg/kg/day to 75-80 mg/kg/day. Because of variable kinetics in children, monitoring of serum levels of free CAP is recommended to avoid the dose related toxicities, bone marrow supression occurring with serum levels of >25 μg/ml and the potentially fatal “gray syndrome” reported with levels of 40-200 μg/ml. During a 20 month period, 592 patients had serum CAP levels measured by HPLC. 54 patients had 1 or more levels ≥ 30 μg/ml, 18/54 had levels ≥40 μg/ml. Only 1 of the patients with evaluable charts (41/54) exhibited pre-existing liver disease (Reye Syndrome). 14/41 patients (34.1%) with levels ≥ 30 μg/ml received a daily CAP dose ≥ 80 mg/kg. Of the remaining 27 patients, 12 (28.5%) were 30 μg/ml and sex, race, admitting diagnosis, or concurrent drug administration. Six patients (14.6%) had more than one risk factor and a higher mean serum CAP level (53.2 μg/ml) than patients with one risk factor (40.8 μg/ml). Risk factors for development of toxic serum concentrations of CAP in children include: 1) dose > 80 mg/kg/day; 2) pre-existing acidemia and/or hypotension; and 3) patient age < 6 months. Early frequent monitoring of serum CAP levels should avoid serious toxicities.
Dr. Gene Amdahl to Speak at ICCAD 2007, Pioneering Achievement Award will Commemorate 40th Anniversary of “Amdahl's Law”

Pioneering Achievement Award will Commemorate 40th Anniversary of Amdahl's Law Dr. Gene Amdahl will receive a SIGDA "Pioneering Achievement" award at the ACM/SIGDA member meeting of ICCAD in San Jose, CA on Tuesday evening, 6 November. This event will be open to the public.