cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacology of selective and non-selective metabotropic glutamate receptor agonists at L-AP4 receptors in retinal ON bipolar cells

Retinal ON bipolar cells possess metabotropic glutamate receptors (mGluRs) which are sensitive to L-2-amino-4-phosphonobutyric acid (L-AP4). Recent studies suggest there are multiple subtypes of L-AP4 receptors. In order to provide a more complete description of the pharmacology of the retinal L-AP4 receptor, we examined the actions of a number of compounds which are active at L-AP4 receptors and other mGluRs. Four groups of compounds were studied: (1) AP4 analogues (e.g. L-AP5, L-SOP, cyclobutylene AP5, and N-Me-AP4), (2) non-selective mGluR agonists (ibotenate and quisqualate), (3) selective mGluR agonists (L-CCG-I), and (4) agonists proposed to be selective for specific mGluR subtypes (DCG-IV and t-ADA). Concentration-response curves were obtained using the b-wave of the electroretinogram (ERG) as an assay for L-AP4 receptor activation. Whole cell voltage clamp recordings from ON bipolar cells in the retinal slice preparation of the mudpuppy were used to determine whether the compounds acted as L-AP4 receptor agonists. All compounds were L-AP4 receptor agonists, except t-ADA which was ineffective. The results reveal pharmacological differences between L-AP4 receptors in mudpuppy ON bipolar cells and those in other systems, consistent with the proposal that there are multiple L-AP4 receptor subtypes. For example, retinal L-AP4 receptors are more potently activated by L-AP5 than L-SOP, whereas L-SOP has been shown to be more potent than L-AP5 in L-AP4 receptors in the lateral perforant path (LPP) of the rat hippocampus. L-SOP is also relatively more potent at the cloned L-AP4 receptors mGluR4, 6, and 7 than in mudpuppy ON bipolar cells in situ. The different potencies of these compounds in retina and LPP is ascribed to both steric and charge factors. The results with DCG-IV and t-ADA are consistent with the proposal that these are subtype-selective agonists, but DCG-IV is likely to be selective only at very low concentrations (< or = 1 microM).
The source and status of values for socially responsible science

Philosophy of Science After Feminism is an important contribution to philosophy of science, in that it argues for the central relevance of advances from previous work in feminist philosophy of science and articulates a new vision for philosophy of science going in to the future. Kourany’s vision of philosophy of science’s future as “socially engaged and socially responsible” and addressing questions of the social responsibility of science itself has much to recommend it. I focus the book articulation of an ethical-epistemic ideal for science, the Ideal of Socially Responsible Science, compare it to recent work in the same vein by Heather Douglas, and argue for some advantages of Kourany’s approach. I then ask some critical question about the view, particularly with respect to the source of values that are to be integrated into science and the status of values that are to be so integrated. I argue that Kourany is too sanguine about where the values that inquirers will use come from and that these values seem to be accorded too fixed a status in her account.
Prehension of half-full and half-empty glasses: time and history effects on multi-digit coordination

We explored how digit forces and indices of digit coordination depend on the history of getting to a particular set of task parameters during static prehension tasks. The participants held in the right hand an instrumented handle with a light-weight container attached on top of the handle. At the beginning of each trial, the container could be empty, filled to the half with water (0.4 l), or filled to the top (0.8 l). The water was pumped in/out of the container at a constant, slow rate over 10 s. At the end of each trial, the participants always held a half-filled container that has just been filled (Empty-Half), emptied (Full-Half) or stayed half-filled throughout the trial (Half-Only). Indices of covariation (synergy indices) of elemental variables (forces and moments of force produced by individual digits) stabilizing such performance variables as total normal force, total tangential force, and total moment of force were computed at two levels of an assumed control hierarchy. At the upper level, the task is shared between the thumb and virtual finger (an imagined digit with the mechanical action equal to that of the four fingers), while at the lower level the action of the virtual finger is shared among the actual four fingers. Filling or emptying the container led to a drop in the safety margin (proportion of grip force over the slipping threshold) below the values observed in the Half-Only condition. Synergy indices at both levels of the hierarchy showed changes over the Full-Half and Empty-Half condition. These changes could be monotonic (typical of moment of force and normal force) or non-monotonic (typical of tangential force). For both normal and tangential forces, higher synergy indices at the higher level of the hierarchy corresponded to lower indices at the lower level. Significant differences in synergy indices across conditions were seen at the final steady state showing that digit coordination during steady holding an object is history dependent. The observations support an earlier hypothesis on a trade-off between synergies at the two levels of a hierarchy. They also suggest that, when a change in task parameters is expected, the neural strategy may involve producing less stable (easier to change) actions. The results suggest that synergy indices may be highly sensitive to changes in a task variable and that effects of such changes persist after the changes are over.
The Existence of Golden Ages and Stability in the Two-Sector Model

I. Introduction, 146. — II. Brief description of the model, 147. — III. The case sw = 0, 148. — IV. The case sp = sw = s, 150. — V. Concluding remarks, 152.
What does high stress police training teach recruits? An analysis of coping

Abstract The use of coping strategies was examined in 143 police recruits subjected to high stress training in a resident police academy. Measures of coping and personal distress were employed under conditions of ostensibly uniform stress conditions. Results indicated that recruits utilized a variety of coping strategies to deal with academy stress, including responses that have the potential to become either adaptive or maladaptive to occupational functioning. Recruits who obtained high scores for personal distress tended to utilize maladaptive styles of coping significantly more often than those who had lower distress scores. These findings suggest that the magnitude of personal distress may be an important factor in determining which array of coping techniques is used by an individual. Police facilities should consider testing alternative training methods to determine which are more effective in helping recruits to cope more efficiently with stress and function satisfactorily in training.
Resistance to thyroid hormone (RTH) syndrome reveals novel determinants regulating interaction of T3 receptor with corepressor.

Abstract Thyroid hormone receptors (T3Rs) both repress and activate gene transcription by interacting with auxiliary factors denoted corepressors and coactivators. Resistance to thyroid hormone (RTH) syndrome in humans is manifested as a failure to respond properly to elevated circulating thyroid hormone. RTH syndrome has been mapped to T3Rβ mutations that alter the transcriptional properties of the receptor, resulting in a dominant negative phenotype. We report here a characterization of a series of RTH mutant T3Rs that exhibit unusual interactions with corepressor. Two mutations in receptor helix 11 (Δ430, Δ432) greatly enhance the ability of the mutant receptors to bind to corepressor. A distinct mutation, V264D, in an ‘omega loop’ region of the receptor, impairs corepressor release but does not fully eliminate the ability to recruit coactivator. These mutations reveal novel determinants that regulate the interaction of the T3R with important ancillary cofactors, and that are disrupted in a human endocrine disease.
An Adenoviral Expression System for AAV Rep78 Using Homologous Recombination

The construction and amplification of adenoviral (Ad) vectors expressing biologically active transgenes that are cytotoxic or inhibit Ad replication can be extremely difficult, if not impossible. In this study, we harnessed the ability of Ad genomes to undergo efficient homologous recombination to reconstitute the adeno-associated virus (AAV) rep78 gene, a cytotoxic gene that strongly inhibits Ad replication, which was divided between two parental, first-generation Ad vectors. A functional open reading frame was generated by recombination only upon co-infection of both parental vectors and after the onset of viral DNA replication. We were able to amplify both parental rep78 vectors to normal titers without any signs of inhibition or toxicity and could use them to generate progeny vectors containing a functional rep78 gene without any Ad genes. Using this vector recombination system in AAV rescue assays demonstrated that no Ad protein was essential for Rep78 mediated rescue of AAV ITR flanked DNA from plasmid or Ad backbones; the amount of rescue product generated was substantially greater in the presence of Ad infection; neither cellular nor viral DNA replication was necessary for rescue to occur; and progeny vector genomes were efficiently co-replicated along with conventional, first-generation Ad vectors.
Impedance to Water Movement in Soil and Plant

The total impedance to water movement from the soil into the plant was compared with that predicted for the soil alone. When soil suction was below 0.6 bar, the impedance was largely in the plant. When suction was greater than 1 or 2 bars, the soil became the limiting factor. Water movement to the plant roots takes place primarily in the liquid phase.
Safety and efficacy of TOR inhibitors and other immunosuppressive regimens in African-American renal transplant recipients.

Abstract African-American renal transplant recipients have higher rates of acute allograft rejection and lower rates of allograft survival compared with Caucasian patients, and these differences have not been eliminated by a new generation of potent immunosuppressive drugs. In particular, African-Americans tend to exhibit higher rejection rates after withdrawal of corticosteroid therapy. Based on promising early results using the combination of sirolimus and low-dose tacrolimus in liver, kidney-pancreas, and islet-cell transplant recipients, our center is conducting a pilot study of this immunosuppression regimen in African-American patients. As of April 2001, there has been only 1 acute rejection episode (2.8%) in this cohort. Long-term follow-up of these patients will be necessary to assess the benefits and risks of this regimen. © 2001 by the National Kidney Foundation, Inc.
Selective sinoatrial node optical mapping to investigate the mechanism of sinus rate acceleration

Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum Ca release (Ca clock) plays an important role in SAN automaticity. However, it is difficult to translate these findings into intact SAN because the SAN is embedded in the right atrium (RA). Cross contamination of the optical signals between SAN and RA prevented the definitive testing of Ca clock hypothesis in intact SAN. We use a novel approach to selectively map intact SAN to examine the Ca clock function in intact RA. We simultaneously mapped intracellular Ca (Cai) and membrane potential (Vm) in 7 isolated, Langendorff perfused normal canine RA. Electrical conduction from the SAN to RA was inhibited with high potassium (10 mmol/L) Tyrode's solution, allowing selective optical mapping of Vm and Cai of the SAN. Isoproterenol (ISO, 0.03 μmol/L) decreased cycle length of the sinus beats from 586±17 ms at baseline to 366±32 ms, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Cai upstroke preceded the Vm in the leading pacemaker site by up to 18±2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 μmol/L), but not ZD7288 (3 μmol/L), a selective If blocker. We conclude that a high extracellular potassium concentration results in intermittent SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation.
High prevalence of hla‐cw1 and cw2 antigens in spondylarthritis

HLA-B27 is frequently, but not invariably, found in patients with spondylarthritic diseases. Recently it has been shown that HLA-C-locus antigens w1 and w2 (w1/2) are in linkage disequilibrium with B27. A group of 139 patients with seronegative arthritis or spondylitis has been studied to determine the clinical and radiographic features associated with these antigens. An increased frequency of spondylarthritis was present in HLA-B27-negative, Cw1/2-positive patients when compared with B27- and Cw1/2-negative patients (P less than 0.01). In addition, a large group of patients who did not fulfill accepted criteria for a specific spondylarthritic syndrome were identified; the frequency of both HLA-B27 and Cw1/2 was greater in these individuals than in healthy blood donors. Thus HLA-Cw1/2 are spondylitis-associated antigens. These findings suggest that the critical genetic locus is neither B27 nor Cw1/2 but is a closely linked gene.
Formation of a flame retardant-cyclodextrin inclusion compound and its application as a flame retardant for poly(ethylene terephthalate)

Abstract We report the formation of an inclusion compound (IC) between a commercial flame retardant (FR) and beta-cyclodextrin (CD). The FR-CD-IC was melt-processed into PET films which were tested for flammability. The flammabilities of pure PET films, PET films containing pure CD, and PET films containing FR applied from a bath and then oven-cured, were also observed. Flammabilities, as measured using a modified AATCC Test Method 34, demonstrated that all but the PET films embedded with FR-CD-IC were either completely or substantially consumed when ignited on a single edge with a 3.8 cm flame applied for 3 s. To our knowledge this is the first demonstration of flame retardance achieved by means of delivering a FR to a polymer in the form of its inclusion compound. The high temperature stability of the FR-CD-IC crystals make them suitable for embedding in a variety of polymers that melt below 300°C. Our results suggest that incorporation of FR-CD-IC directly into polymer films or fibers during their melt-processing may be a means to protect them from burning that is superior to post-fabrication application of FRs. In addition, liquid FRs, which are difficult to incorporate and retain in solid polymers, may be included in their high-melting ICs formed with CDs and embedded directly into polymer samples. More broadly, we would expect that a host of other polymer additives may be more effectively delivered in the form of their CD-ICs.
An analysis of gas-lubricated foil-journal bearings

The foil journal bearing is essentially a series of thin overlapping circular metal foils, one end of which is cantilevered to the bearing and the other end rests on an adjacent foil. Typically, the radial load at the high temperature end (turbine) of a gas turbine engine is supported by a roller bearing. The high temperatures encountered at the turbine end result in reduced roller bearing life and also necessitate elaborate cooling and lubricating systems to keep the bearing temperatures within reasonable limits. Foil-journal bearings are simple, lightweight and well suited for such high temperature applications, and since they are self-acting air bearings the need for a lubricant supply system is obviated. The hydrodynamic pressure force in the air film generated by the journal rotation deflects the compliant foil surface resulting in a change in film thickness, and hence the pressure solution to the problem is of the elasto-hydro-dynamic (EHD) type. The nonlinear compressible finite-length Reynolds equ...
Constraints on PDFs from W and Z rapidity distributions at CDF

The rapidity distributions of W and Z bosons produced in proton anti-proton collisions at CDF are presented. The rapidity distribution of Z bosons, measured for the first time over the entire kinematic range, is better described by NLO QCD (and also by QCD with gluon resummation) than by leading order QCD. The W charge asymmetry data as a function of rapidity strongly constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34. The W data are used to rule out recently proposed models for charge and flavor symmetry violation of the sea quark distributions in the nucleon.
Evaluation of flowmeter-head loss effects in the flowmeter test

In this study, we develop an axisymmetric groundwater flow model to numerically simulate the hydraulic head loss across the flowmeter during a flowmeter test. Using it, we investigate the influence of flowmeter induced hydraulic head losses and filter pack effects on the calculated drawdown distributions in the vicinity of the pumping well and on the flowmeter test estimates of layer horizontal hydraulic conductivity, Ki; in three different aquifer‐well systems: a homogeneous aquifer; a homogeneous aquifer with a filter pack surrounding the well; and a two-layer aquifer with a filter pack surrounding the well. We confirm that the Ki estimates can be significantly biased due to the head loss across the flowmeter. This head loss induces a non-uniform flow pattern in the vicinity of the well, which violates the horizontal flow assumption invoked by flowmeter test interpretation methodologies. The effect of the hydraulic head losses alone (i.e. no cross-flow through the filter pack) can lead to Ki estimation errors as great as a factor of three even in a homogeneous aquifer. The coupled effect of hydraulic head losses and cross-flow through the filter pack can lead toKi estimation errors of up to a factor of 10 or greater. In actual flowmeter tests, these head losses can be reduced by increasing the annulus of the flowmeter, by operating the flowmeter without a packer, or by choosing a small enough pumping rate. q 1999 Elsevier Science B.V. All rights reserved.
Students' perception of professional advocacy following a political advocacy course

Abstract Objective To analyze the characteristics of pharmacy students who had taken a political advocacy elective compared with those who did not on their engagement in advocacy activities. Methods An elective in political advocacy is offered to first-, second-, and third-year pharmacy students. A survey was developed to assess the students' perceived knowledge of the issues affecting the pharmacy profession, willingness to vote in an election, current level of advocacy, and likelihood for advocacy after graduation. The survey also assessed the students' current leadership activities, involvement in local and national pharmacy organizations, and prior experience with professional pharmacy issues. The survey was voluntarily administered to the student body. Comparisons between the elective class and student body were made using descriptive statistics and t -test. Results Of the 462 students, 100 (21.6%) completed the online survey. Students who took the elective rated their knowledge of current issues significantly higher than those who did not. A greater percentage of students who took the course reported participating in advocacy activities within the last month compared with those who did not (41.2% vs. 14.8%). Finally, the students who took the course expressed significantly more personal responsibility for being politically active compared with those who did not. Implications Despite the constraints of current pharmacy curriculums, the results of this study demonstrate that offering an elective in political advocacy is beneficial in educating pharmacy students about issues affecting the profession and instilling the importance of being involved as a student pharmacist, as well as in the future.
Evidence that chorion-decidual prolactin release is calcium dependent.

The regulation of PRL release from chorion-decidual explants was evaluated in organ-cultures. Agents previously shown to stimulate pituitary release in vitro (TRH, theophylline, estradiol, and vasoactive intestinal polypeptide) were all without effect on chorion-decidual PRL release. Media free of calcium, however, resulted in 44% decreased chorion-decidual PRL release. Conversely, 2.5 HIM CaCl2 produced a 64% increase in PRL release (P < 0.01). Also, calcium chelationwith EGTA (0.125–1.0 HIM) produced a dose-related decrease in choriondecidual PRL release. This decrease was greatest at 1.0 HIM (P < 0.01), being 56% of control. In contrast, the calcium-calmodulin complex inhibitor trifluoperazine (10 μM) did not significantly alter chorion-decidual PRL release. These studies and previous reports in the literature suggest that different control mechanisms govern pituitary and chorion-decidual PRL release; however, an exception appears to be a common role for calcium. (J Clirv Endocrinol Metab 54: 820,1982)
Status of risk assessment analysis for mechanical systems in nuclear plants

Abstract In the frame of a short review of the status of risk assessment analysis for mechanical systems in nuclear power plants the following concepts are discussed: confidence limits; Bayesian statistical approach; material degradation effects; Fracture mechanics; and fault tree analysis.
Sea star factor blocks development of T-dependent antibody secreting clones by preventing lymphokine secretion.

Abstract Sea star factor (SSF), a protein of 39 kDa purified from macrophage-like coelomocytes of the echinoderm Asterias forbesi , has potent immunosuppressive effects on T-dependent but not T-independent antibody responses in vivo . SSF at a concentration of 0.5 μg/ml markedly inhibits T-dependent antibody production in vitro by fluorescein (Flu)-specific B cells responding in clonal microculture to antigenic stimulation with Flu-conalbumin via the conalbumin-specific T cells D10.G4.1 (D10). At this concentration of SSF, Ig secretion induced by a T cell-independent stimulus, lipopolysaccharide (LPS), is not affected. Inhibition of antibody production in T-dependent microcultures by SSF can be completely overcome in a dose-dependent fashion by addition of lymphokine-rich supernatants from stimulated cultures of D10 cells. The possibility that SSF suppresses production of requisite cytokine growth factors from T cells was substantiated by the finding that SSF diminishes concentrations of stimulatory cytokines detectable in supernatants from antigen-stimulated cultures. Nevertheless, levels of intracytoplasmic mRNA for IL-4 and IL-5 are not detectably altered by concentrations of SSF that suppress antibody production. Furthermore, when cultures of D10 cells stimulated in the presence of SSF are subjected to freezing and thawing to release intracytoplasmic lymphokines, total levels of stimulatory cytokines are not lower than those in cultures without SSF. These results suggest that SSF inhibits antibody responses by limiting the availability of lymphokines produced by helper T cells. The mechanism for this inhibition may involve either direct effects of SSF on T cells or a block in effective T cell-B cell interaction.
Responsible innovation: from concept to practice

This book provides a business studies perspective on responsible innovation (RI) and what it might mean in practice to integrate the concept into organizations. The first hundred pages provide an o...
Survey of organic wastewater contaminants in biosolids destined for land application.

In this study, the presence, composition, and concentrations of organic wastewater contaminants (OWCs) were determined in solid materials produced during wastewater treatment. This study was undertaken to evaluate the potential of these solids, collectively referred to as biosolids, as a source of OWCs to soil and water in contact with soil. Nine different biosolid products, produced by municipal wastewater treatment plants in seven different states, were analyzed for 87 different OWCs. Fifty-five of the OWCs were detected in at least one biosolid product. The 87 different OWCs represent a diverse cross section of emerging organic contaminants that enter wastewater treatment plants and may be discharged without being completely metabolized or degraded. A minimum of 30 and a maximum of 45 OWCs were detected in any one biosolid. The biosolids used in this study are produced by several production methods, and the plants they originate from have differing population demographics, yet the percent composition o...
Quasi-Geostrophic Topographically Generated Mean Flow over the Continental Margin

Abstract Observations of oppositely directed, monthly mean alongshore currents and wind stress over the continental margin off the Pacific coast of North America motivate the theoretical examination of mean flow generation by topographic lee-wave drag. We formulate a barotropic model for wind-forced shelf-slope flow over variable topography. Our central objective is an analytical expression for mean flow generation in a simple case. We specify a linear cross-shelf slope with sinusoidal alongshore variations and use the approximation of Hart, which yields a system with only parametric cross-shelf dependence when the alongshore scales are short compared to the cross-shelf scales. The inviscid unforced equations have two constants of the motion and reduce to a quartic Hamiltonian system similar to that of Duffing's equation. For weak new-resonant time-periodic forcing, we use the method of averaging to obtain evolution equations for the amplitudes of small oscillations. All steady solutions of the averaged e...
d-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia

Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50mg or placebo in a counterbalanced order on two consecutive weeks 1h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant d-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training.
Comfort and Seating Distance in Living Rooms The Relationship of Interactants and Topic of Conversation

Two experiments were reported. In each experiment, the subjects were shown photographs of living rooms. The seat occupied by another person was indicated. In the first experiment, the subject was asked to choose an unoccupied seat in the room; in the second, he was asked to imagine himself in a second seat and to indicate his degree of comfort with that situation. The results of Experiment 1 show that both the topic of conversation and the indicated relationship of the person in the other chair were significantly related to distance between the chosen chairs. The results of Experiment 2 show that discomfort increased with increasing distance between chairs, and that comfort was related to both the topic of conversation and to the relationship indicated between the subject and the occupant of the other chair. Findings are discussed in the context of Hall's theory of interpersonal distances.
Interval Scaling Using Pair Comparisons or Pair Comparison Treatment of Complete Ranks Under Case III Assumptions

Two of the better approaches to the scaling of stimuli are the methods of pair comparison and pair comparison treatment of complete ranks under the assumptions of Thurstone's Case III. This paper outlines a computer program with four data input options which scales up to 40 stimuli using these methods. The program will also compute an absolute scale zero point if the user employs the Horst method of balanced values (acceptance or rejection of pairs) in addition to the pair comparison procedure. Output of the program is detailed and includes, in addition to scale values and standard deviations, several matrices which allow Case IV or V scaling by hand with minimal effort.
SOCS proteins and caveolin-1 as negative regulators of endocrine signaling

Recently, a new class of regulatory molecules has emerged; these molecules, termed SOCS proteins, function as suppressors of cytokine signaling. SOCS proteins negatively regulate the Janus kinase signal transducer and activator of transcription (JAK–STAT) signaling cascade. Interestingly, it appears that other proteins, such as caveolin-1, can also function as suppressors of cytokine signaling by inhibiting the kinase activity of JAK family members. This might result from the ability of caveolin-1 to function as a broad-spectrum kinase inhibitor through the caveolin-scaffolding domain.
Mechanochemistry of Persistent Plasmid Movement

The segregation of DNA prior to cell division is essential to the faithful inheritance of the genetic materials. In many bacteria, the segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and DNA-binding ParB protein, which stimulates the hydrolysis activity of ParA. Both in vivo and in vitro experiments have shown that the ParA/ParB system can drive the persistent movement of the plasmids in a directed fashion, just like a processive motor protein. However, the underlying mechanism remains unknown. We have developed the first theoretical model on ParA/ParB-mediated motility. We establish that the coupling between the ParA/ParB biochemistry and its mechanical action works as a robust engine. It powers the directed movement of plasmids, buffering against the diffusive motion. Our work thus sheds light on a new emergent phenomenon, in which elaborate mechanochemical couplings of non-motor proteins can work collectively to propel cargos to designated locations, an ingenious way shaped by evolution to cope with the lack of a processive motor protein in bacteria.
High-resolution Microwave Spectra of H and OH Absorption Lines of Cassiopeia A

IN a recent communication Weinreb, Barrett, Meeks and Henry1 reported the discovery of the 18-cm lines of the hydroxyl (OH) radical in the radio absorption spectra of Cassiopeia A, and the result was quickly confirmed by several others2–4. Here we present the results of investigations of the −0.8 km/sec absorption line from Cassiopeia A at both H and OH line frequencies with a frequency resolution as narrow as 1.87 kc/s. From these observations we can derive the kinetic temperature of the absorbing gas. The equipment used in the OH observations was the same as used previously1, except for the modification necessary to obtain the higher frequency resolution. In our earlier work a 100-kc/s portion of the spectrum was examined with a resolution of 7.5 kc/s, and in the work reported here we also examined either a 50-kc/s portion with a resolution of 3.75 kc/s or a 25-kc/s portion with a resolution of 1.87 kc/s. It is found that the − 0.8 km/sec absorption line at OH frequencies is in reality composed of two lines, separated by 7.5 kc/s, having approximately equal intensities, and having line-widths (full-width at half maximum) of 4.2 kc/s and 4.8 kc/s after correction for the receiver resolution. The observed spectra for the three frequency resolutions used are shown in Fig. 1.
Protection of ischemic rat heart by cardioplegic doses of pentobarbital.

Abstract We examined the ability of pentobarbital in extremely high concentrations (over 10 times the anesthetic dose) to act as a cardioplegic agent. Isolated rat hearts treated with 500 mg/liter of pentobarbital showed excellent recovery of heart function (heart rate and aortic pressure) after 25 min of global ischemia at 37°C. The effect of 375 mg/liter of pentobarbital was marginal, and lower concentrations of pentobarbital (125–250 mg/liter) did not improve the recovery of heart function even though the drug prevented ventricular tachycardia which is frequently observed upon reperfusion of ischemic heart.
Increased alkalinity in the Mississippi.

The increase in alkalinity export from the Mississippi River reported by P. A. Raymond and J. J. Cole (“Increase in the export of alkalinity from North America's largest river,” Reports, 4 July, p. [88][1]) has important implications for the biogeochemistry of the region. The broader-scale
BiCom3HV - A 36V Complementary SiGe Bipolar- and JFET-Technology

An oxide isolated complementary SiGe base bipolar technology is presented that incorporates JFETs, poly-and thin-film resistors, capacitors and Schottky Barrier diodes for high-precision, high-voltage, high speed, low-noise analog applications at significantly reduced package size.
SUPPORT PROVIDED TO RURAL, ADOLESCENT MOTHERS BY THEIR MALE PARTNERS

Rural areas provide special problems and benefits to adolescent mothers. Lack of services is offset by more social stability. In a 24-month-old project a female nurse practitioner and a male social worker working in a rural school district have focused on family supports, including the adolescent's male partner. In 90% of 60 adolescent pregnancies the relationship between the mother and partner lasted over 9 months. Most males were over 20; only 20% were 18 or less. During pregnancy 77% of males provided emotional support; 52% provided financial support. Ten percent of the couples were married and 30% lived together. The males were at 62% of deliveries; 70% provided emotional support at the time. The first 3 months after birth were stressful with 28% of couples separating. Three months after delivery 50% of partners provided financial support and 48% helped with child care. At this time, 21% are married, 33% live together, 45% of the males provide some child care, 45% provide financial support, and 57% are involved with the mother. During the 24-month study there was known physical violence in 20% of the relationships. Mild physical violence was directed at the child by the male partner in 10%. There was more involvement of the male during pregnancy and delivery than later. The decrease in male interest between 1 and 3 months post partum was a stress for the mother. Physical violence between adolescent partners was a significant problem.
Introduction of all-hydrocarbon i,i+3 staples into alpha-helices via ring-closing olefin metathesis.

The introduction of all-hydrocarbon i,i+3 staples into α-helical peptide scaffolds via ring-closing olefin metathesis (RCM) between two α-methyl,α-pentenylglycine residues incorporated at i and i+3 positions, which lie on the same face of the helix, has been investigated. The reactions were found to be highly dependent upon the side-chain stereochemistry of the amino acids undergoing RCM. The i,i+3 stapling system established here provides a potentially useful alternative to the well-established i,i+4 stapling system now in widespread use.
Estimation of client-assessed hearing aid performance based upon unaided variables.

The purpose of this study was to investigate the possibility of estimating client-assessed hearing aid performance before hearing aids are purchased. Aided performance was represented by the Profil...
Forcing the Least Measurable to Violate GCH

Starting with a model for “GCH + k is k+ supercompact”, we force and construct a model for “k is the least measurable cardinal + 2k = K+”. This model has the property that forcing over it with Add(k,k++) preserves the fact k is the least measurable cardinal.
A shape optimization approach based on natural design variables and shape functions

Abstract The general problem of concern is to find the optimum shape of an elastic body, which requires minimizing an objective function subject to stress, displacement, frequency, and manufacturing constraints. The basic approach so far has been to choose a set of geometric design variables that define the shape of the structure. Typically the design variables have been chosen as coefficients of splines and polynomials, coordinates of ‘control’ nodes, and other geometric parameters. An automatic finite element discretization scheme that uses geometric entities such as lines, arcs, splines, and blending functions, is then used to relate changes in position of interior grid points in the finite element mesh to changes in the design variables. In this paper, a set of natural design variables is chosen as the design variables defining the shape. Specifically, the design variables are the magnitudes of a set of fictitious loads applied on the structure. The displacements produced by these fictitious loads, or natural shape functions, are added onto the initial mesh to obtain the new shape. Consequently, a linear relationship is established between changes in grid point locations and design variables through a finite element analysis. Plane elasticity problems are solved using the new approach. The quality of the finite element meshes produced and other salient features of the shape optimal design problem are discussed.
Differential trafficking of the vesicular monoamine transporter-2 by methamphetamine and cocaine.

High-dose administration of cocaine or methamphetamine to rats acutely (≤24 h) alters vesicular dopamine transport. This study elucidates the nature of these changes. Results reveal a differential redistribution of the vesicular monoamine transporter-2 (VMAT-2) within striatal synaptic terminals after drug treatment. In particular, cocaine shifts VMAT-2 protein from a synaptosomal membrane fraction to a vesicle-enriched fraction, as assessed ex vivo in fractions prepared from treated rats. In contrast, methamphetamine treatment redistributes VMAT-2 from a vesicle-enriched fraction to a location that is not retained in a synaptosomal preparation. These data suggest that psychostimulants acutely and differentially affect VMAT-2 subcellular localization.
Growth hormone responses to varying doses of oral arginine.

Abstract Intravenous (IV) arginine invokes an increase in growth hormone (GH) concentrations, however, little is known about the impact of oral arginine ingestion on the GH response. Objective The purpose of this study was to determine the dose of oral arginine that elicits an optimal GH response and to determine the time course of the response. Design Eight healthy males (18–33 years – 24.8 ± 1.2 years) were studied on 4 separate occasions. Following an overnight fast at 0700 h, a catheter was placed in a forearm vein. Blood samples were taken every 10 min for 5 h. Thirty minutes after sampling was initiated, the subject ingested a dose of arginine (5, 9 or 13 g) or placebo (randomly assigned). Results Mean resting GH values for the placebo, 5, 9 and 13 g day were 0.76, 0.67, 2.0 and 0.79 μg/L (n = 6), respectively. Integrated area under the curve was not different with 13 g (197.8 ± 65.7 min μg/L), yet it increased with 5 and 9 g compared with the placebo (301.5 ± 74.6, 524.28 ± 82.9 and 186.04 ± 47.8 min μg/L, respectively, P Conclusion In conclusion, 5 and 9 g of oral arginine caused a significant GH response. A 13 g dose of arginine resulted in considerable gastrointestinal distress in most subjects without augmentation in the GH response. The rise in GH concentration started ∼30 min after ingestion and peaked ∼60 min post ingestion.
HIERARCHY AND ‘HEROIC SOCIETY‘: MANAM VARIATIONS IN SEPIK SOCIAL STRUCTURE

Anthropologists have come to recognize that in addition to the prevalence of egalitarian relations, many New Guinea societies also exhibit elements of hierarchy as well. This article discusses the nature of hierarchy in some Sepik societies through the comparative analysis of the social structure of four Sepik area societies on the northeast coast of Papua New Guinea. Using Sahlins' definition of ‘heroic societies’ based upon a principle of ‘hierarchical solidarity’, the article argues that the form of hierarchy found in Manam Island society is different in type from that of the neighboring societies of Boroi, Murik and Wogeo. An additional diagnostic feature of heroic societies is what Sahlins refers to as ‘heroic history. In Manam the cultural form this takes is a ‘heroic’ variation of the myth of two brothers common throughout the area.
Baseline correlates with quality of life among men and women with medication-controlled hypertension. The trial of nonpharmacologic interventions in the elderly (TONE).

OBJECTIVES: To examine Quality of Life (QOL) and its correlates among older adults with medication-controlled hypertension. DESIGN: Baseline data from the TONE clinical trial. MEASUREMENTS: Demographic variables (age, race, income), hypertension treatment (medication class, years treated), health status (obesity, physical symptoms), and QOL status (MOS-Short-Form 36, Jenkins Sleep Disturbance, and CES-D Depression). PARTICIPANTS: A total of 975 men and women, aged 60 to 81 years and free of major diseases and disability, with a screening blood pressure (BP) of < 145/85 mm Hg, treated medically for hypertension with antihypertensive medication. RESULTS: On average, TONE participants reported a QOL level on the SF-36 that was similar to or better than that reported by older adults in the general population. However, there was a strikingly high prevalence of physical complaints or symptoms: 90.3% of men and 93.3% of women experienced one or more physical symptoms or complaints, and nearly 50% reported that such symptoms had disrupted their daily functioning. Among variables considered, only the physical symptoms index score, number of severe symptoms, and obesity status were correlated consistently with QOL among TONE men and women. Lower QOL scores were associated with higher symptom scores and with obesity. Neither medication class nor age were appreciably associated with QOL status. CONCLUSIONS: Physical symptoms, rather than medication class and age, were the strongest correlates of QOL in TONE. This underscores the importance of identifying the etiology of symptoms as a means to improve the QOL of older hypertensive persons rather than substituting medication. The association of poorer physical well-being with obesity suggests that weight reduction to manage BP may also improve QOL for some individuals.
Structure-activity relationships of amino acid receptor sites on an identifiable cell body in the brain of the land snail Helix aspersa

Abstract 1. 1. Cell 7 in the brain of Helix aspersa was used as a functional single-unit chemoreceptor to study membrane receptor sites which respond to glutamic acid. 2. 2. Conductance measurements made by injecting pulses of constant current across the cell membrane were used to follow the activation of the receptor site. 3. 3. Almost all structural derivatives which interfered with any of the three electrostatically charged sub-moieties of the glutamate molecule were ineffective at the cell membrane. 4. 4. There appears to be great structural similarity among the dicarboxylic amino acid receptor sites found in cat, crab, locust, cockroach and snail neurons.
Crystallization behavior of binary metallic glasses containing Pt

Abstract Binary MPt glasses were made by rapid quenching from liquid, where M is Ti, Zr, and Hf. Glass forming compositions were found near eutectics in TiPt, ZrPt and HfPt. Isothermal crystallization for Zr 75 Pt 25 was studied at a temperature range from 780 to 792 K. The non-isothermal transformation was measured by differential scanning calorimetry with heating rates from 5 to 160 K/min. Activation energy for crystallization was obtained from the non-isothermal heating, which is consistent with that from the isothermal annealing.
Alcohol and Single Cell Protein Production by Kluyveromyces in Concentrated Whey Permeates with Reduced Ash

Abstract Five Kluyveromyces yeasts were grown in concentrated whey permeates under aerobic and anaerobic conditions to produce single cell protein and ethyl alcohol. Kluyveromyces fragilis NRRL Y 2415 produced the highest yield of alcohol, 9.1% vol/vol, and Kluyveromyces bulgaricus ATCC 1605 gave the highest yield of biomass, 13.5 mg/ml. High ash, apparently through sodium and potassium effects, inhibited production of biomass and alcohol. A .77% ash was optimum. Lactose utilization was more rapid under aerobic than anaerobic conditions. Ammonium sulfate and urea supplementation were without effect on yeast growth or were slightly inhibitory. A 1% peptone inclusion gave the highest biomass yield with minimum alcohol production.
Isolation and culture of adult rat hippocampal neurons

Inability to culture adult central neurons and the failure of injured neurons to regenerate in the brain could be due to genetic controls or environmental inhibitors. We tested the environmental inhibitor hypothesis by attempting to regenerate adult rat neurons in B27/Neurobasal culture medium, a medium optimized for survival of embryonic neurons. To isolate neurons from their numerous connections, papain was the best of six different proteases screened on slices of hippocampus for survival of isolated cells after 4 days of culture. Use of a density gradient enabled separation of oligodendroglia and some enrichment of neurons and microglia from considerable debris which was inhibitory to sprouting and viability. With these techniques, about 900000 viable neurons were isolated from each hippocampus of any age rat from birth to 24-36 months, near the median mortality. FGF2 was found to enhance viability at least 3-fold to 40-80%, independent of age, without affecting the length of the processes. Neurons were cultured for more than 3 weeks. These methods demonstrate that hippocampal neurons can regenerate axons and dendrites if provided with adequate nutrition and if inhibitors are removed. They also will enable aging studies. Therefore, the concept of environmental growth restriction may be more appropriate for neurons in the brain than the concept of a genetic block that precludes regeneration of processes.