cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessment of primary and metastatic ovarian cancer by positron emission tomography (PET) using 2-[18F]deoxyglucose (2-[18F]FDG)

The potential of positron emission tomography (PET) to distinguish benign from malignant ovarian tissue was evaluated by comparing the results of F-18 fluoro-2-D-deoxyglucose (F-18-FDG) PET scans with computed tomography and surgical findings. If sufficiently sensitive, this method might play a role in localizing metabolically active tumor sites for diagnosis, staging, and follow-up of ovarian cancer. Fifty-one patients had imaging studies prior to laparotomy for suspected ovarian cancer. PET scans were done with an ECAT 931-08-12 or ECAT EXACT (Model 921, Siemens/CTI, Knoxville, TN) after iv injection of 185-370 MBq of F-18-FDG. (ECAT is a trade name for "emission computerized axial tomograph.") Data were acquired in dynamic scanning mode and time activity curves (TACs) were evaluated in multiple regions of interest identified by visual interpretation of the PET scans. Scan interpretation, standardized uptake values, and TAC profiles were related to surgical and histological findings. The results of this pilot study show good correlation between PET and histological findings. The positive predictive value of PET for ovarian cancer was 86% and, perhaps more important, the negative predictive value was 76%. This early work indicates that PET may be useful in the management of patients with ovarian neoplasms by identifying occult foci of metabolically active tumor that do not appear on morphological studies.
Integration of multiscale dendritic spine structure and function data into systems biology models.

Comprising 1011 neurons with 1014 synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the massive big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.
Classical Representation of a Quantum System at Equilibrium

A quantum system at equilibrium is represented by a corresponding classical system, chosen to reproduce the thermodynamic and structural properties. The objective is to develop a means for exploiting strong coupling classical methods (e.g., MD, integral equations, DFT) to describe quantum systems. The classical system has an effective temperature, local chemical potential, and pair interaction that are defined by requiring equivalence of the grand potential and its functional derivatives with respect to the external and pair potentials for the classical and quantum systems. Practical inversion of this mapping for the classical properties is effected via the hypernetted chain approximation, leading to representations as functionals of the quantum pair correlation function. As an illustration, the parameters of the classical system are determined approximately such that ideal gas and weak coupling RPA limits are preserved (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Structural Basis for Enhanced HIV-1 Neutralization by a Dimeric Immunoglobulin G Form of the Glycan-Recognizing Antibody 2G12

The human immunoglobulin G (IgG) 2G12 recognizes high-mannose carbohydrates on the HIV type 1 (HIV-1) envelope glycoprotein gp120. Its two antigen-binding fragments (Fabs) are intramolecularly domain exchanged, resulting in a rigid (Fab)2 unit including a third antigen-binding interface not found in antibodies with flexible Fab arms. We determined crystal structures of dimeric 2G12 IgG created by intermolecular domain exchange, which exhibits increased breadth and >50-fold increased neutralization potency compared with monomeric 2G12. The four Fab and two fragment crystalline (Fc) regions of dimeric 2G12 were localized at low resolution in two independent structures, revealing IgG dimers with two (Fab)2 arms analogous to the Fabs of conventional monomeric IgGs. Structures revealed three conformationally distinct dimers, demonstrating flexibility of the (Fab)2-Fc connections that was confirmed by electron microscopy, small-angle X-ray scattering, and SPR binding studies. We conclude that intermolecular domain exchange, flexibility, and bivalent binding to allow avidity effects are responsible for the increased potency and breadth of dimeric 2G12. In addition, we present this as the first known crystal structure of an IgG dimer.
An external focus of attention attenuates balance impairment in patients with Parkinson's disease who have a fall history

Objectives Studies using young, non-impaired adults have shown that by directing attention to the outcome of movements (external focus) rather than directing attention to the movements involved in a specific skill (internal focus), motor skill acquisition is enhanced. The purpose of this study was to investigate the generalisability of these attentional focus findings to balance in subjects with Parkinson’s disease. Design Experimental, repeated measures design. Setting Physiotherapy research facility. Participants Twenty-two subjects diagnosed with idiopathic Parkinson’s disease. Interventions Subjects were tested under three attentional focus conditions; no instruction, internal focus and external focus. Main outcome measure Balance equilibrium scores from three computerised dynamic posturography conditions. Results A significant condition x attentional focus interaction was found ( F [4, 84] = 2.86, P < 0.05), indicating increased sway with internal focus relative to no focus instructions (control) under the eyes-open condition. More importantly, when only subjects with a history of falls were considered, there was a significant interaction between condition and attentional focus ( F [4, 36] = 4.40, P < 0.01). Post hoc tests revealed that the external focus instructions resulted in less sway than both internal focus and no attentional focus instructions under sway-referenced conditions. Conclusion These findings support previous research studies on attentional focus. In particular, it was demonstrated that the balance of subjects with Parkinson’s disease and a fall history can be enhanced by instructing subjects to adopt an external focus.
A Specific Isoform of Nonmuscle Myosin II-C Is Required for Cytokinesis in a Tumor Cell Line

Nonmuscle myosin IIs play an essential role during cytokinesis. Here, we explore the function of an alternatively spliced isoform of nonmuscle myosin heavy chain (NMHC) II-C, called NMHC II-C1, in the A549 human lung tumor cell line during cytokinesis. NMHC II-C1 contains an insert of 8 amino acids in the head region of NMHC II-C. First, we show that there is a marked increase in both the mRNA encoding NMHC II-C1 and protein in tumor cell lines compared with nontumor cell lines derived from the same tissue. Quantification of the amount of myosin II isoforms in the A549 cells shows that the amounts of NMHC II-A and II-C1 protein are about equal and substantially greater than NMHC II-B. Using specific siRNAs to decrease NMHC II-C1 in cultured A549 cells resulted in a 5.5-fold decrease in the number of cells at 120 h, whereas decreasing NMHC II-A with siRNA does not affect cell proliferation. This decreased proliferation can be rescued by reintroducing NMHC II-C1 but not NMHC II-A or II-B into A549 cells, although noninserted NMHC II-C does rescue to a limited extent. Time lapse video microscopy revealed that loss of NMHC II-C1 leads to a delay in cytokinesis and prolongs it from 2 to 8-10 h. These findings are consistent with the localization of NMHC II-C1 to the intercellular bridge that attaches the two dividing cells during the late phases of cytokinesis. The results suggest a specific function for NMHC II-C1 in cytokinesis in the A549 tumor cell line.
Specific versus general procedures in instructions

A good deal of research in cognitive psychology has demonstrated that, although learners can solve problems that are just like the ones they have been trained on, they often have great difficulty solving new types of problems. People also have difficulty trying to understand instructions or training materials that try to teach a procedure at a level that is general enough to apply to many different kinds of cases. These two findings lead to a quandary for people designing instructions for procedural tasks such as operating computer software: Instructions should be written with a good deal of specificity so that new users can understand and use them right away, but at the same time the user will have great difficulty generalizing what they have learned to novel cases. Experiment 1 seems to echo this quandary. Computer novices, in this study, were able to follow specific instructions for using a word processor more easily than general instructions. However, they had great difficulty generalizing the specific instructions to novel tasks. Experiment 2 demonstrates that when specific instructions are rewritten to help users form a more general procedure, novices can easily do new tasks and still maintain their initial quality of performance. A production rule formalism is used to represent the knowledge users obtain from instructions and to explore the conditions under which these productions can be generalized. Experiment 2 suggests that this knowledge can be used to improve the generalizability of instructions.
HUMAN LACIORERRIN FORTIFICATION OF FORMULAS PROMOTES THYMIDINE UPTAKE INTO DNA OF RAT INTESTINAL CRYPT CELLS

Previous investigations have demonstrated that lactoferrin in human colostrum stimulates thymidine uptake into the DNA of harvested mature rat intestinal crypt cells. The effect of cow milk- and soy-based infant formulas on thymidine incorporation into DNA of rat intestinal crypt cells was studied. Crypt cells were harvested from adult male rats using the method of eversion and vibration. The cells were incubated in Trowell's T-8 medium with 10% fetal calf serum in a Dubnoff shaking water bath at 37°C gased with 95% O2 and 5% CO2. Each 50-ml incubation tube contained 4-5 × 105 cells in 1 ml of medium. When the skim fractions of the cow milk- and soy-based formulas were added to the incubated cells, 3H-thymidine incorporation into DNA was inhibited. This inhibition was reversed with the addition of human lactoferrin in amounts comparable to those found in human colostrum. CONCLUSION: Cow milk- and soy-based infant formulas inhibit thymidine uptake into DNA of rat intestinal crypt cells. Addition of human lactoferrin to the formulas reverses the inhibition.
Explicit solutions for the response of simple systems subjected to nonstationary random excitation

Abstract A new approach is presented for obtaining explicit solutions for the second-moment statistics of the response of single-degree-of-freedom systems subjected to modulated white noise excitation. The solutions depend on only three basic integrals. Explicit expressions can be found for a number of interesting cases for which these integrals can be evaluated in closed form. The method also facilitates numerical computation in cases where an explicit solution cannot be found. Some illustrative examples are presented
Subchronic treatment with either clozapine, olanzapine or haloperidol produces a hyposensitive response of the rat cortical cells to N-methyl-D-aspartate.

Using the technique of intracellular recording in in vitro brain slice preparations, we examined the effects produced by repeated administration of the antipsychotic drugs clozapine, olanzapine and haloperidol, on N-methyl-D-aspartic acid-induced responses in pyramidal cells of the rat medial prefrontal cortex. Rats were anesthetized and decapitated 24h after the conclusion of daily intraperitoneal injection with either clozapine (25mg/kg), olanzapine (1, 5 or 10mg/kg) or haloperidol (0.5mg/kg) for 21 days, and the slices from medial prefrontal cortex were used for electrophysiological recordings. The concentration-response curves for N-methyl-D-aspartic acid to activate cortical cells shifted markedly to the right in rats which received the subchronic antipsychotic drug treatment, compared with those obtained from rats which received repeated injections of vehicle (1ml/kg/day, i.p. for 21 days). In addition, repeated exposure to antipsychotic drugs caused a significant reduction in the ability of these antipsychotic drugs to augment the N-methyl-D-aspartic acid-induced inward current in pyramidal cells of the rat medial prefrontal cortex. Repeated administration of haloperidol, but not clozapine or olanzapine, significantly hyperpolarized the resting membrane potential and increased membrane resistance in pyramidal cells of the medial prefrontal cortex. Moreover, subchronic treatment with haloperidol, but not clozapine or olanzapine, depressed (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-induced responses. The desensitized response of medial prefrontal cortex cells to N-methyl-D-aspartic acid could be the result of a compensatory response to the facilitating action of antipsychotic drugs on N-methyl-D-aspartic acid receptor-mediated transmission. The inhibitory action of haloperidol on (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid responses may also contribute to the rightward shift of the N-methyl-D-aspartic acid concentration-response curve.Thus, the present study suggests that the atypical antipsychotic drugs, clozapine and olanzapine, as well as the typical antipsychotic drug haloperidol strongly modulate glutamatergic transmission after prolonged treatment. This might be an important factor in the mechanisms by which these drugs alleviate symptoms in schizophrenic patients.
Inhibition of morphine tolerance and dependence by diazepam and its relation to μ-opioid receptors in the rat brain and spinal cord

Abstract We have recently observed that concomitant administration of diazepam to morphine pellet implanted rats results in the inhibition of the development of morphine tolerance and dependence. We have now analyzed μ-opioid receptors in rats treated with morphine and diazepam for 5 days by using [ 3 H ] -DAMGO for binding studies. Male Sprague–Dawley rats were made tolerant and dependent by subcutaneous (s.c.) implantation of six morphine pellets (two pellets on the first day, and four on the second day). Diazepam (0.25 mg/kg b.wt) was injected once daily intraperitoneally (i.p.) for 5 days. Control rats were implanted with placebo pellets and injected once daily with saline or diazepam (i.p.). Animals were administered s.c. naloxone (10 mg/kg) to induce naloxone-precipitated withdrawal syndrome on the final day of the experiment (day 5). There was an up-regulation of μ-receptor (Bmax increased) in the spinal cord of morphine tolerant (+139%) and dependent (+155%) rats compared to saline treated animals. Diazepam treatment abolished the up-regulation of μ-receptors in spinal cord of morphine treated rats. In the cortex, Bmax was not affected in morphine tolerant or dependent rats but it decreased by 38% in morphine tolerant and 65% in morphine dependent rats treated with diazepam. The Kd of μ-receptors increased in the cortex, striatum and hypothalamus of morphine dependent rats. Diazepam treatment decreased the Kd of μ-receptors in the cortex of morphine tolerant and hypothalamus of morphine-dependent rats. These results suggest that diazepam treatment antagonizes the up-regulation of CNS μ-receptors observed in morphine tolerant rats. In addition, morphine tolerance and dependence may be associated with conversion of μ-opioid receptors to μ*-constitutive opioid receptors that are less active, and this conversion is prevented in the brain of animals treated with diazepam.
Cascade Effects in Certain Atomic Lifetime Measurements

A semiclassical discussion is given of a simple case of the Hanle effect when the population of the level of interest varies with time because of decays to it from higher levels excited by collisions. It is found that the width of the intensity-vs-applied-field curve is no longer simply related to the lifetime of this single level, but depends on the relative populations and lifetimes of all other participating levels. It is shown by examples that, unless these effects are taken into account, the lifetimes deduced from the measurements can be greatly in error.
Toward Optimizing Man's Tactile Communication

Man is tactually literate! This has been known for some time-for at least as long as the blind have been known to "read" with their finger tips scanning Braille symbols. Helen Adams Keller not only reads with her fingers and writes wich them through a typewriter, but also she "listens" with the skin of her hands and "speaks" with her fingers in a semiprivate system of encoding and decoding the kinds of informarion ordinarily called "linguistic" or "literate," Man's integument can be substituted in linguistic matters for his ears, his eyes, or for both. Geldard (1957) has referred to rhe work of both Gaulc (1936) and Katz (1930, pp. 90-104) who thirty years ago investigated the feasibility of circurnventing deafness by applying speech sounds directly to the surface of the skin through stimulus-producing electromechanical transducers. Their results, and those of more recent investigations (Wiener, et al., 1949-195 1 ) , suggest that this is not feasible. In spite of the many similarities between hearing and skin sensations-and there are many as Bekesy (1959) has shown-such attempts appear futile in the light of our present knowledge. It does not appear possible to make any simple direct transcriptions of speech-patterned sound energy that when applied to the skin result in meaningful percepts of speech patterns. The limiting features of the skin seem to be the slowness wich which its nerves react relative to the auditory nerves, and the nonindependence of stimulus frequency and intensity in the cutaneous sense (Anderson & Munson, 1951; Bekesy, 1959; Geldard, 1957). A caution is necessary, however, that this conclusion not be overgeneralized. There is at least one datum to indicate that speech sounds may be directly perceived through the skin, albeit the sensory transcriptions may nor be simple and direct. Whether complex or simple, cutaneous transcriptions of such speechpatterned sound energies apparently are perceived and interpreted directly as "speech" in at least one instance! Specifically, Helen Keller is able to interpret speech that she "hears" through whatever stimuli act on three fingers--one placed on the throat just over che larynx, one placed just in front of the lips, and the third placed just beside the nose of the speaker. The resulting cutaneous sensations are ap'This paper is based on a presentation made by the author during an invitational research symposium on cutaneous sensitivity held at the US Army Medical Research Laboratory, Fort Knox, Ky., February, 1960. 'The author expresses his appreciation to the Emory University Research Committee for providing funds in support of this publication.
Alterations in humoral immune responses associated with recurrent pregnancy loss.

Abstract Objective: To investigate the reactivity of maternal antibodies with endometrium-derived antigens and to correlate their association with recurrent pregnancy loss (RPL). Design: Prevalence study. Setting: Academic research center. Patient(s): Nulliparous women (n = 10), women with RPL (n = 15), pregnant women (n = 8), and multiparous women with a normal obstetric history (n = 20). Intervention(s): None. Main Outcome Measure(s): Reactive antibodies were analyzed by Western immunoblot techniques and quantitated by densitometry. Result(s): Antibodies from women with RPL and multiparous women recognized antigens ranging from 10–120 kd on normal endometrium and endometrial tumors. Antibodies from most women with RPL (10/15) and from multiparous women (15/20) recognized 65-kd and 80-kd proteins in normal endometrium. Antibodies from women with RPL recognized 21-kd and 28-kd antigens (12/15 and 13/15, respectively) in endometrial tumors at a significantly greater rate (than did antibodies from multiparous women (5/20 and 8/20, respectively). Women with RPL had significantly lower levels of asymmetric IgG compared with controls. Conclusion(s): Recurrent pregnancy loss may be linked with the failure to elicit asymmetric IgG and a unique immunologic recognition of endometrial antigens.
Comparing the impacts of regulation and climate on ice-jam flooding of the Peace-Athabasca Delta

Abstract The Peace-Athabasca Delta (PAD) in northern Alberta is one of the world's largest inland freshwater deltas, home to large populations of waterfowl, muskrat, beaver, and free-ranging wood bison. Following construction of the Bennett Dam in the late 1960s, a paucity of ice-jam flooding in the lower Peace River has resulted in prolonged dry periods and considerable reduction in the area covered by lakes and ponds that provide habitat for aquatic life in the PAD region. Past studies have shown that both regulation and climate have contributed to the drying trend, via increased freezeup levels and reduced breakup flows, respectively. However, it has not so far been possible to assess the relative impacts of these two factors. This question is addressed herein by developing quantitative relationships based on the concept of conditional probability. The new methodology is first tested against observed frequencies of ice-jam floods both before and after regulation; it is subsequently applied to quantify the effects of climate and of regulation on the post-regulation reduction in ice-jam flood frequency. The results indicate that both factors have contributed significantly to the drying of the PAD, with regulation having had the more pronounced effect. Complications that may arise from secondary effects of regulation on breakup flows or of climate on freezeup levels are discussed and quantified. It is shown that such effects do not alter the overall conclusions of the paper.
Effects of Chronic (Dietary) Choline Availability on the Transport of Choline Across the Blood‐Brain Barrier

The effects of dietary choline availability on the transport of choline across the blood-brain barrier (BBB) were investigated using the intracarotid injection technique. Maintenance of rats on choline-deficient, basal choline, or choline-supplemented diets for 28-32 days led to respective increases in blood levels of choline and correlative increases in the velocity of transport of choline measured using a buffer injectate. When serum from these rats was included in the injectate and transport determined in control animals, there was a marked inhibition of choline transport that was related to the concentration of choline in the diets. Results suggest that the activity of the choline carrier at the BBB is antagonized by an inhibitory substance in serum whose concentration or activity may be modified by chronic alterations in circulating levels of choline and whose presence may normally regulate the velocity of choline transport.
Structural properties of compartmental models

Abstract This article treats structural properties of the inverse of a compartmental matrix and how they relate to properties of coefficients of the transfer function of the compartmental system. Newly formulated conditions are presented for certain of these parameters to be zero or positive. Also results are given on the interdependence of transfer function coefficients and how this relates to the identifiability problem. Answers to some questions raised in the recent literature about coefficient dependence are discussed.
A constitutive model for the large deformation of a self-healing gel

We developed a 3D finite strain constitutive model to study the deformation of a hydrogel that contains two types of molecular crosslinks with one set of crosslinks much stronger than the other. Upon mechanical loading, the weaker crosslinks first break but can reform after breakage, thus endowing the gel with self-healing ability. An example is a recently developed ionically cross-linked triblock copolymer hydrogel, where ionic cross-links can form between the polyelectrolyte mid-blocks due to electric interaction. These physical bonds provide an additional set of crosslinks, which is analogous to the tightly cross-linked network in a double network gel and is necessary for toughness enhancement. However, unlike covalent bonds, these ionic cross-links can reform after they break. By keeping track of the time evolution of the breakage and reformation of these physical crosslinks, our model is able to address the macroscopic softening (hardening) behavior due to breaking (healing) of the physical bonds. In particular, we demonstrate our model for a uni-axial tensile test and show that strain softening in a tensile test can be suppressed by sufficiently slow loading rates. Our model is also able to capture the hysteresis and plasticity in a loading-unloading cycle.
Perishable-asset revenue management: Generic and multiple-price yield management with diversion

Abstract In any situation of fixed capacity and a perishable service or product, firms want to avoid spoilage of the service or product and receive the most revenue possible in the face of uncertain demand. Stimulation of demand from price-sensitive customers, however, through discount prices to customers that reserve early can help fill capacity. This is attractive if non-price-sensitive customers can be prevented from diverting to the lower rates. This paper provides generic results for deciding how many discount units to sell (the so-called yield-management problem) and extends the generic problem in several ways: (1) to situations with continuous, not discrete resources, (2) to treatment of yield management jointly with overbooking, and (3) to problems with diversion with more than two price classes. Simulation studies using airline data suggest that our decision rules perform better than previous rules now used in practice.
New payload attribution methods for network forensic investigations

Payload attribution can be an important element in network forensics. Given a history of packet transmissions and an excerpt of a possible packet payload, a payload attribution system (PAS) makes it feasible to identify the sources, destinations, and the times of appearance on a network of all the packets that contained the specified payload excerpt. A PAS, as one of the core components in a network forensics system, enables investigating cybercrimes on the Internet by, for example, tracing the spread of worms and viruses, identifying who has received a phishing e-mail in an enterprise, or discovering which insider allowed an unauthorized disclosure of sensitive information.Due to the increasing volume of network traffic in today's networks, it is infeasible to effectively store and query all the actual packets for extended periods of time in order to allow analysis of network events for investigative purposes; therefore, we focus on extremely compressed digests of the packet activity. We propose several new methods for payload attribution, which utilize Rabin fingerprinting, shingling, and winnowing. Our best methods allow building practical payload attribution systems, which provide data reduction ratios greater than 100:1 while supporting efficient queries with very low false positive rates. We demonstrate the properties of the proposed methods and specifically analyze their performance and practicality when used as modules of a network forensics system ForNet. Our experimental results outperform current state-of-the-art methods both in terms of false positives and data reduction ratio. Finally, these approaches directly allow the collected data to be stored and queried by an untrusted party without disclosing any payload information nor the contents of queries.
Ultralow-loss polycrystalline silicon waveguides and high uniformity 1x12 MMI fanout for 3D photonic integration.

We have investigated the feasibility of multimode polysilicon waveguides to demonstrate the suitability of polysilicon as a candidate for multilayer photonic applications. Solid Phase Crystallization (SPC) with a maximum temperature of 1000°C is used to create polysilicon on thermally grown SiO2. We then measure the propagation losses for various waveguide widths on both polysilicon and crystalline silicon platforms. We find that as the width increases for polysilicon waveguides, the propagation loss decreases similar to crystalline silicon waveguides. At a waveguide width of 10µm, polysilicon and crystalline silicon waveguides have propagation losses of 0.56dB/cm and 0.31 dB/cm, respectively, indicating there is little bulk absorption from the polysilicon and is the lowest propagation loss for polysilicon demonstrated to date. In addition, the first 1x12 polysilicon MMI is demonstrated with a low insertion loss of −1.29dB and a high uniformity of 1.07dB. These results vindicate the use of polysilicon waveguides of varying widths in photonic integrated circuits.
Masking-induced sensitivity changes in Limulus photoreceptors.

Abstract Limulus photoreceptor sensitivity was investigated at various times during the response to a 400 msec flash of light. This procedure is the same as that used psychophysically when masking by light is studied and masking functions were obtained that were very similar to typical psychophysical masking functions. However, even at this most distal level, sensitivity was not determined by any one variable alone. Instead, sensitivity was dependent on receptor potential amplitude and receptor saturation and receptor dynamics.
Midazolam administered into the amygdala impairs retention of an inhibitory avoidance task.

This experiment investigated the amnestic effects of injections of the benzodiazepine midazolam administered into the amygdala prior to training on an inhibitory avoidance task. Male Sprague-Dawley rats were implanted bilaterally with cannulae aimed at the amygdala. After 1 week recovery a buffer solution or midazolam (3 or 10 μg/0.5 μl) was injected bilaterally 5 min before a single training trial in a two-compartment inhibitory avoidance apparatus. The pretraining intra-amygdala injections of midazolam did not affect the training step-through latencies. However, on a 48-h retention test the step-through latencies of the midazolam-treated animals were significantly lower than those of the buffer controls. These findings are consistent with other recent evidence indicating that the amygdala is involved in mediating the amnestic effects of benzodiazepines.
Virulence characteristics of Salmonella following deletion of genes encoding the tRNA modification enzymes GidA and MnmE

Salmonella is an important foodborne pathogen causing major public health problems throughout the world due to the consumption of contaminated food. Our previous studies have shown that deletion of glucose-inhibited division (gidA) gene significantly altered Salmonella virulence in both in vitro and in vivo models of infection. In Escherichia coli, GidA and MnmE have been shown to modify several bacterial factors by a post-transcriptional mechanism to modify tRNA. Therefore, we hypothesize that GidA and MnmE complex together to modulate virulence genes in Salmonella using a similar mechanism. To test our hypothesis, and to examine the relative contribution of GidA and MnmE in modulation of Salmonella virulence, we constructed gidA and mnmE single mutants as well as a gidA mnmE double mutant strain of Salmonella. Results from the in vitro data displayed a reduction in growth, motility, intracellular replication, and invasion of T84 intestinal epithelial cells in the mutant strains compared to the wild-type Salmonella strain. The in vivo data showed a significant attenuation of the mutant strains as indicated by the induction of inflammatory cytokines and chemokines, as well as in the severity of histopathological lesions in the liver and spleen, compared to mice infected with the wild-type strain. Also, a significant increase in the LD50 was observed in mice infected with the mutant strains, and mice immunized with the mutants were protected against a lethal dose of wild-type Salmonella. A pull-down assay indicated that Salmonella GidA and MnmE bind together, and HPLC analysis revealed that deletion of gidA and/or mnmE altered Salmonella tRNA modification. Overall, the data suggest MnmE and GidA bind together and use a post-transcriptional mechanism to modify tRNA to regulate Salmonella pathogenesis.
DNA adduct formation by alachlor metabolites.

Abstract The extent of DNA adduct formation by alachlor [ArN(CH2OCH3)C(O) CH2Cl wherein Ar is 2, 6-diethylphenyl] and its metabolites is used as a guide to deduce the causal agent(s) in the carcinogenicity of this major herbicide. [14C-phenyl]Alachlor is compared to its two metabolic cleavage products, [14C-phenyl]2-chloro- N -(2,6-diethylphenyl) acetamide (CDEPA) [ArNHC(O)CH2Cl] and [14C-phenyl] 2,6-diethylaniline (DEA) (ArNH2), and to [14C-methoxy]alachlor in various in vitro and in vivo systems. Horseradish peroxidase and hydrogen peroxide activate DEA, but not CDEPA or alachlor, for formation of adducts with calf thymus DNA, which probably involves 2,6-diethylnitrosobenzene (ArNO) as an intermediate. Mouse liver microsomes and NADPH are both required to enhance the binding from each labeled preparation to calf thymus DNA; 4-fold higher labeling is observed from [14C-methoxy]- than from [14C-phenyl]alachlor. This 4-fold preferential DNA labeling from the 14C-methoxy compound is likewise found in the liver of mice treated intraperitoneally. Mouse liver protein and hemoglobin are also labeled, in vivo , with [14C-phenyl]alachlor, -CDEPA and -DEA, and, as with the DNA, the labeling of these proteins is 1.5- to 2-fold higher with [14C-methoxy]alachlor. Metabolic studies indicate that ArN(CH2OCH2OH)-C(O)CH2Cl is an intermediate in forming CDEPA and presumably formaldehyde in the mouse liver microsomal mixed-function oxidase system and in yielding the O -glucuronide of ArN(CH2OH)C(O)CH2Cl in the urine of alachlor-treated mice. These findings point to the N -CH2OCH2OH metabolite or formaldehyde as a reactive intermediate in forming a DNA-adduct and as a candidate proximate carcinogen.
Linezolid: an oxazolidinone antimicrobial agent.

Abstract Background: Linezolid is the first oxazolidinone anti-infective agent marketed in the United States. It is indicated for the treatment of nosocomial pneumonia, complicated skin and skin-structure infections caused by methicillin-sensitive or methicillin-resistant Staphylococcus aureus and other susceptible organisms, and vancomycin-resistant Enterococcus faecium infections. It also is indicated for the treatment of uncomplicated skin and skin-structure infections caused by methicillin-sensitive S aureus or Streptococcus pyogenes , and community-acquired pneumonia caused by penicillin-sensitive Streptococcus pneumoniae . Objective: This article reviews the pharmacologic properties and clinical usefulness of linezolid. Methods: Using the terms linezolid, PNU-100766 , and oxazolidinone , we performed a literature search of the following databases: MEDLINE ® (1966 to September 2000), HealthSTAR ® (1993 to September 2000), Iowa Drug Information Service (1966 to September 2000), International Pharmaceutical Abstracts (1970 to September 2000), PharmaProjects (January 2000 version), and meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996 to 2000). Results: Linezolid has a unique structure and mechanism of action, which targets protein synthesis at an exceedingly early stage. Consequently, cross-resistance with other commercially available antimicrobial agents is unlikely. It is primarily effective against gram-positive bacteria. To date, resistance to linezolid has been reported in patients infected with enterococci. The pharmacokinetic parameters of linezolid in adults are not altered by hepatic or renal function, age, or sex to an extent requiring dose adjustment. Linezolid is metabolized via morpholine ring oxidation, which is independent of the cytochrome P450 (CYP450) enzyme system; as a result, linezolid is unlikely to interact with medications that stimulate or inhibit CYP450 enzymes. Compassionate-use trials and other clinical studies involving mainly adult hospitalized patients with gram-positive infections have shown that linezolid administered intravenously or orally is effective in a variety of nosocomial and community-acquired infections, including those caused by resistant gram-positive organisms. Reported adverse effects include thrombocytopenia, diarrhea, headache, nausea, vomiting, insomnia, constipation, rash, and dizziness. Preliminary pharmacoeconomic data indicate that a significantly higher percentage of patients receiving linezolid therapy versus comparator could be discharged from the hospital by day 7 ( P = 0.005). Conclusions: Linezolid appears to be effective while maintaining an acceptable tolerability profile. Due to the risk of bacterial resistance, linezolid should be reserved for the treatment of documented serious vancomycin-resistant enterococcal infections.
Inflation-Gap Persistence in the US

We estimate vector autoregressions with drifting coefficients and stochastic volatility to investigate whether US inflation persistence has changed. We focus on the inflation gap, defined as the difference between inflation and trend inflation, and we measure persistence in terms of short- to medium-term predictability. We present evidence that inflation-gap persistence increased during the Great Inflation and that it fell after the Volcker disinflation. We interpret these changes using a dynamic new Keynesian model that highlights the importance of changes in the central bank's inflation target. (JEL E12, E31, E52, E58)
Variable-PRI processing for meteorologic Doppler radars

In this communication we described how, with nonuniform sampling, the concept of bandlimited extrapolation can be used to obtain unambiguous Doppler velocity estimates in the supra-Nyquist region. The proposed method coherently processes a multi-PRI sample using a generalized form of periodogram analysis. The work is described in the context of meteorologic Doppler processing and includes a discussion of effective suppression for stationary ground clutter when multi-PRI schemes are used. >
Form Drag due to Flow Separation at a Headland

Observational and model estimates of the form drag on Three Tree Point, a headland located in a tidal channel of Puget Sound, Washington, are presented. Subsurface, Three Tree Point is a sloping ridge. Tidal flow over this ridge gives rise to internal lee waves that lead to wave drag and enhanced mixing. At the same time, horizontal flow separation produces a headland eddy that distorts the surface height field in the lee of the point. Two observational methods for estimating the portion of the form drag associated with deformation of the surface height field, referred to here as the “external” form drag, are also introduced. Drogued drifters and ship-mounted acoustic current profiles from different days are used to indirectly map the flood-tide surface height field. Data are derived from a depth shallow enough that baroclinic pressure gradient forcing may be neglected, and yet deep enough that wind stress may also be ignored. This leaves an approximate balance between the acceleration and surface height pressure gradient, permitting, in this case, two independent estimates of the surface height (to within a constant). These fields are used to calculate the external form drag at the headland. Drag estimates from both observational datasets agree well. External form drag decreases offshore of the headland as expected, and is highly dependent on tidal phase, with maximum drag leading peak flood currents by 1–2 h at this location. Form drag is much larger than model estimates of the frictional drag, implying that it is the dominant mechanism extracting energy from the barotropic tide. A kinematic argument is also presented to show why the external form drag should increase in importance relative to the frictional drag as the topographic slope and tidal excursion increase.
Synthetic shuffling and in vitro selection reveal the rugged adaptive fitness landscape of a kinase ribozyme

The relationship between genotype and phenotype is often described as an adaptive fitness landscape. In this study, we used a combination of recombination, in vitro selection, and comparative sequence analysis to characterize the fitness landscape of a previously isolated kinase ribozyme. Point mutations present in improved variants of this ribozyme were recombined in vitro in more than 10 14 different arrangements using synthetic shuffling, and active variants were isolated by in vitro selection. Mutual information analysis of 65 recombinant ribozymes isolated in the selection revealed a rugged fitness landscape in which approximately one-third of the 91 pairs of positions analyzed showed evidence of correlation. Pairs of correlated positions overlapped to form densely connected networks, and groups of maximally connected nucleotides occurred significantly more often in these networks than they did in randomized control networks with the same number of links. The activity of the most efficient recombinant ribozyme isolated from the synthetically shuffled pool was 30-fold greater than that of any of the ribozymes used to build it, which indicates that synthetic shuffling can be a rich source of ribozyme variants with improved properties.
Caught in their own speed trap: The intersection of speed enforcement policy, police legitimacy, and decision acceptance

Empirical work examining the effects of police legitimacy has primarily focused on traffic stop procedures with less attention given to traffic enforcement policies. The current study takes advantage of a natural experiment in which a rural town with a strict speed enforcement policy was labeled a "speed trap" through the introduction of a billboard advertisement funded by the American Automobile Association. Drawing on theories of police legitimacy, we hypothesize the label will result in an abrupt-permanent increase in speeding citation contestation rates, despite the fact that the billboard actually increases predictability of citation issuance. Results of an interrupted time-series analysis indicate statistically significant abrupt-permanent increases in the speeding citation contestation rates for the intervention city. Further analyses reveal that significant intervention effects are confined to drivers with higher opportunity to contest tickets (in-state drivers) and to majority subgroups (Whites and men). The implications of these findings for policy and police-citizen relationships are discussed.
Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro

Moringa (Moringa oleifera Lam.) is an edible plant used as both a food and medicine throughout the tropics. A moringa concentrate (MC), made by extracting fresh leaves with water, utilized naturally occurring myrosinase to convert four moringa glucosinolates into moringa isothiocyanates. Optimum conditions maximizing MC yield, 4-[(α-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate content were established (1:5 fresh leaf weight to water ratio at room temperature). The optimized MC contained 1.66% isothiocyanates and 3.82% total polyphenols. 4-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate exhibited 80% stability at 37°C for 30 days. MC, and both of the isothiocyanates described above significantly decreased gene expression and production of inflammatory markers in RAW macrophages. Specifically, both attenuated expression of iNOS and IL-1β and production of nitric oxide and TNFα at 1 and 5 μM. These results suggest a potential for stable and concentrated moringa isothiocyanates, delivered in MC as a food-grade product, to alleviate low-grade inflammation associated with chronic diseases.
Effects of methanol on embryonic mouse palate in serum-free organ culture.

The present study examines the developmental toxicity of methanol in the palate using a serum-free organ culture model. Gestation day 12 CD-1 mouse embryos were dissected and mid-craniofacial tissues were cultured in BGJ medium at 37 C for 4 days with medium changes at 24 hr intervals. Cultures were exposed to methanol from 0-20 mg/ml for 6 hr, 12 hr, 1 or 4 days. Some cultures were exposed to ethanol for 4 days at doses ranging from 0-15 mg/ml. All cultures were gassed with a 50% O2, 5% CO2, and 45% N2 upon addition of fresh medium and prior to the addition of alcohol. In general the ethanol was more potent than methanol for inhibition of protein and DNA synthesis and palatal fusion. The study demonstrated that methanol can selectively affect specific sensitive cell populations and has effects on proliferation and cell fate.
eReply. Re: Efforts to further enhance the safety of sternal re-opening in the paediatric age group

We thank the author for his comments [1] regarding our report [2]. We must say that the technique for chest re-entry he describes is very similar to what we do in our institution, as well as the judicious use of preventive femoral cannulation in selected cases. We think that the technique of haemostasis with inflation of a Fogarty catheter may be, as the saying goes, one more weapon in the arsenal of the paediatric cardiac surgeon and as such, it has been reported. Conflict of Interest: none declared.
Dynamic Modeling of Flat Belt Drives Using the Elastic-Perfectly-Plastic Friction Law

An analysis of a physically-motivated friction model called the Elastic/Perfectly-Plastic (EPP) friction model was performed on a steadily rotating flat belt drive. The EPP friction law is modeled as an elastic spring in series with an ideal Coulomb damper. The belt kinematics were developed and the nonlinear equations of motion and equilibrium solutions were derived using Hamilton’s Principle. Unlike the belt mechanics analyzed with Coulomb friction, the current study predicts the absence of adhesion zones. A stability analysis demonstrates that the non-linear equilibrium solution found is stable under local perturbation. A two-pulley belt drive with equal radii is analyzed and the dynamic response is studied. The results are compared to those computed using a dynamic finite element model. Excellent agreement between the two methods is documented.Copyright © 2009 by ASME