cssi/SciSciGPT-SciSciNet huggingface dataset:
Phylogenetic distribution of bicuculline-sensitiveγ-amino-butyric acid (GABA) receptor binding

Bicuculline-sensitive [3H]GABA receptor binding was studied in membrane fractions prepared from vertebrate whole brain or invertebrate cephalic ganglia. In tissue not treated with Triton X-100, a significant amount of bicuculline-displaceable [3H]GABA binding was detected in the brains of all vertebrates studied, with the hagfish brain binding over twice as much [3H]GABA as the spiny dogfish, the next oldest species. All other vertebrates bound similar amounts of [3H]GABA, being one-third to one-fourth that observed in the hagfish. In contrast, after Triton treatment, the hagfish displayed the least amount of bicuculline-sensitive [3H]GABA binding and, under those conditions, the amount of binding observed increased in an evolutionary fashion. No measurable bicuculline-sensitive GABA receptor binding was noted in any invertebrate studied. These results suggest that bicuculline-sensitive GABA receptors are present in the brains of all vertebrates and that during the course of evolution there developed a Triton-sensitive substance(s) whose presence modifies the kinetic properties of this receptor site.
Interactions of α-methylfluorene-2-acetic acid with adenylate cyclase

Abstract α-Methylfluorene-2-acetic acid (MFA), a new anti-inflammatory agent, enhanced the stimulation of adenylate cyclase activity from guinea pig heart by isoproterenol, epinephrine and norepinephrine, but did not cause increases in either basal or histamine-stimulated activity. Propranolol blocked the effects of isoproterenol plus MFA on heart cyclase activity. MFA did not enhance PGE 1 - or PGE 2 -stimulated cyclase activity from guinea pig lung; effects of MFA on isoproterenol-stimulated activity were obscured by a marked inhibition of basal activity. d -MFA and l -MFA were equipotent enhancers of isoproterenol-responsive heart cyclase activity. Increases in isoproterenol-stimulated cyclase activity from heart in the presence of MFA appeared reversible; decreases in basal activity were irreversible. The action of MFA was not due to inhibition of cyclic nueleotide phosphodiesterase activity, nor did MFA appear either to affect catecholamine degradation or to antagonize an endogenous cytoplasmic inhibitor of catecholamine action. It is possible that MFA perturbed the membrane milieu of the cyclase complex so as to have enhanced catecholamine binding to hormone receptors or coupling of the binding event to cyclic AMP synthesis.
Hemodynamic Analysis and Design of a Paracorporeal Artificial Lung Device

We have extended our model of the ovine pulmonary circulation to include a model of a paracorporeal artificial lung (AL) and its attachments to the natural pulmonary circulation in two configurations: in series and in parallel. Our model of the natural lung (NL) circulation is first shown to be in agreement with hemodynamic and input impedance data from the open literature. We then study design efficacy of the AL in terms of its housing and attachments. A sensitivity analysis of the modified pulmonary circulation model reveals that there are three key parameters: inlet graft length (IGL) and the compliances of the inlet compliance chamber (CC) and housing of the artificial lung. Based on literature reports, we assume the right ventricle is well-matched to the impedance of the natural pulmonary circulation and adjust the parameters of the modeled AL circuit to achieve the best least-squares fit to natural pulmonary input impedance data. Best-fit parameters produce impedance curves that fit natural impedance well, particularly below 3 Hz, where both compliance and graft length have their largest effects. Of these parameters, the impedance profile is most sensitive to IGL. However, the compliances are important, as well, particularly at low frequencies.
Dynamic Modeling Analysis for Control of Chemical Vapor Deposition

A nonlinear dynamic model of the chemical vapor deposition (CVD) process has been developed to aid design of a closed-loop control system. A lumped control volume analysis is used to capture important mass and fluid transients and spatial affects, while a simplified single variable equation is used to represent the complex reaction chemistry. Steady-state experimental results and model predictions are compared and the control implications of the process dynamics are discussed.
Multiple product inventory policies with unit load and storage space considerations

Abstract In this paper the appropriate unit load for each product in a multi-product inventory system is determined and used to calculate the best policy given limited storage space. An inventory system with constant demand and replenishments rates is considered. The Economic Unit Load (EUL) method is revised to include multiple container types and the Equal Order Interval (EOI) method is extended to consider unit loads and finite replenishment rates. The methods are compared using total cost and average space utilization as the criteria.
Information in two-stage programming under uncertainty

The random variables in two-stage programming under uncertainty are generally treated in a passive manner in that no information regarding the random variables or the process generating the random variables may be obtained. This paper develops the economics of information for the case in which the probability distributions are discrete. A multinomial process is assumed to generate the random variables, and the parameter vector of that process is assumed to be unknown. A Dirichlet prior distribution on the parameter vector is used, and the computation of the value of information thus involves a Dirichlet-multinomial distribution on the random variables. An example involving producing to meet uncertain demands is presented.
High Rates of Extinction and Threat in Poorly Studied Taxa

Abstract: Mass extinctions in the past have been characterized by abnormally high species extinction rates within almost all taxa. Attempts to estimate relative rates of extinction and threat among modern taxa, such as insects, plants, and vertebrates, are impeded by differences in the quality of information about each group. Insects and marine groups, for example, have much smaller percentages of known threatened species but also have many more undescribed species than do plants or vertebrates. I tested the possibility that all major groups have equally high rates of extinction and threat. The first test was a model assuming that differences in apparent global extinction and threat rate are caused by two sampling biases that produce artificially low rates in understudied taxa: (1) a common-species bias in which taxonomists tend to record common (more extinction-resistant) species first and (2) evaluative neglect, which is a tendency to spend relatively less effort evaluating the extinction and threat status of recorded species in understudied taxa. Global extinction and threat data from a number of groups generally follow the pattern predicted by this model. The second test shows that in direct measurements of extinction and threat between taxa in well-studied regions, such as the United States and United Kingdom, the apparent global disparity among taxa is greatly reduced. Indeed, many globally understudied taxa, such as insects and other invertebrates, have higher rates of threat than many other taxa, including mammals, in these well-studied areas. These two tests provide quantitative support for previous suggestions that the wide disparity in rates of species extinction and threat among groups represents an artifactual distortion of the actual rates. Specific suggestions for improved estimates of actual threat include (in order of increasing accuracy): use of well-studied proxy taxa such as mammals; comparison of threat data among taxa only in well-studied regions; and, especially important, increased efforts to evaluate the threat status of recorded species of understudied taxa.
Shape-slant relations under reduction conditions

Two experiments are reported which attempted to test implications of the shape-slant invariance hypothesis. Both experiments employed an apparatus in which variations in the slant and in the width settings of a rectangle were highly ambiguous and subject to instructional sets. In the first experiment, the stimulus was varied in both its width and its slant to achieve matches to four standard angles; the resultant width settings were found to be close to the projected widths of the obtained angles of slant. In the second experiment, width and slant were varied to match four standard widths; the projected widths of the obtained angles of slant did not differ from the obtained width settings.
Optical Properties of Thin Films of Cadmium Sulfide

Thin evaporated films of CdS on glass were studied in the wavelength range 4000A to 7500A. Measurements of film thickness and reflectivity as a function of wavelength were used to determine the index of refraction and the extinction coefficient. Density measurements and aging tests were also carried out. The effects on film properties of a variation of the rate of deposition were investigated.
Electron Microscopic Detection of Glycoconjugates in the Chicken Lens

The cytochemical localization of glycoconjugates in the 14-day old embryonic chick lens was analysed by lectin-gold labelling. Con A/HRP gold particles, specific for D-mannose labelled the interior of the rough endoplasmic reticulum, membranes of the Golgi complex, secretory vesicles and the plasma membranes of the lens epithelial cell. The lens capsule was heavily labelled. Lens fiber cell membranes were also labelled. In contrast LFA, specific for neuraminic acid, did not bind to the endoplasmic reticulum or nuclear membrane. Labelling of the Golgi complex, secretory vesicles and capsule was observed. The plasma membranes of epithelial and fiber cells were extensively labelled, and probably reflects the presence of glycolipids such as gangliosides.
Telling truth from Ys: an evaluation of whether the accuracy of self-reported semen exposure assessed by a semen Y-chromosome biomarker predicts pregnancy in a longitudinal cohort study of pregnancy

Objectives Adolescents may use condoms inconsistently or incorrectly, or may over-report condom use. This study used a semen exposure biomarker to evaluate the accuracy of female adolescents’ reports of condom use and predict subsequent pregnancy. Methods The sample comprised 715 sexually active African-American female adolescents, ages 15–21 years. At baseline, 6 months and 12 months, participants completed a 40-min interview and were tested for semen Y-chromosome with PCR from a self-administered vaginal swab. We predicted pregnancy from semen exposure under-report using multivariate regression controlling for oral contraception, reported condom use and coital frequency. Results At the 3 surveys, 30%, 20% and 15% of adolescents who reported always using condoms tested positive for semen exposure. At 6 month follow-up, 20.4% and 16.2% of the adolescents who under-reported semen exposure reported pregnancy, a higher pregnancy rate than accurate reporters of semen exposure, even accurate reporters who reported never using condoms (14.2% and 11.8%). Under-reporters of semen exposure were 3.23 (95% CI (1.61, 6.45)) times as likely to become pregnant at 6-month follow-up and 2.21 (0.94, 5.20) times as likely to become pregnant at 12-month follow-up as accurate reporters who reported not using contraception, adjusting for self-reported coital frequency. Conclusions Adolescents who under-report semen exposure may be at uniquely high risk for unplanned pregnancy and STIs, and may also under-report coital frequency. Condom efficacy trials that rely on self-report may yield inaccurate results. Adapted to a clinical setting, the Y-chromosome PCR could alert women to incorrect or inconsistent condom use.
Designing home availability services

We have explored the challenges of designing domestic services to help family and friends determine mutually agreeable times to call one another. In a prior study, we identified activities in the home that predict availability to an external interruption. In our follow-up study, we used a cooperative design activity to see which, if any, of these home activities the family member is willing to share when engaged in mealtime or leisure routine. The data people are willing to reveal is more detailed for mealtime, than leisure activities. Furthermore, the shared availability service needs to be accessible throughout the home, in either compact, portable form or integrated with other services in various room locations. Accuracy and reliability of the shared information, along with device independent caller identification are also essential design requirements. While not unique to the home, the desire to personalize and present a socially acceptable availability status is extremely important.
Effect of a simulated glaze ice shape on the aerodynamic performance of a rectangular wing

The effect of a simulated glaze-ice accretion on the flowfield of a 3D wing is studied experimentally. The model used for these tests was a semispan wing of effective aspect ratio five, mounted from the sidewall of a subsonic wind tunnel. The model has a NACA 0012 airfoil section on a rectangular untwisted planform with interchangeable leading edges to allow for testing both the baseline and the iced-wing geometry. A four-beam two-color fiberoptic laser Doppler velocimeter (LDV) was used to map the flowfield along three spanwise cuts on the model. Measurements on the centerline of the clean model compared favorably with theory and centerline measurements on the iced model compared well with measurements on a similar 2D model. The flow has the largest separation bubble at the model midspan with the smallest separation bubble occurring near the root and the wing tip.
Enhanced oxidation resistance of nanocrystalline FeBSi materials

Abstract The oxidation behavior of the nanocrystalline FeBSi alloy prepared using the crystallization method has been investigated. The results indicate that the microstructures of the materials have a strong effect on the oxidation behavior. Because of the unique nature of the microstructure, the nanocrystalline FeBSi alloy shows a significantly enhanced oxidation resistance over those of the amorphous and coarse-grained crystalline FeBSi alloys with the same composition.
ODMR studies of antisite-related luminescence in GaP☆

Abstract By the use of ODMR, we have detected and identified two different antisite defects which contribute to newly-reported infrared luminescence observed in GaP. The antisite proper, PGa, gives rise to a spin- 1 2 resonance; the associated luminescence originates in the DA pair recombination of an electron trapped at the deep double donor P+Ga with a distant shallow acceptor. An impurity-associated centre of the form PGa · YP is observed in a spin-triplet state via a distinct luminescence band which originates in electron-hole recombination localised at the defect.
Aperture Synthesis by Object Rotation in Coherent Imaging

Doppler processing is an established method for obtaining spatial resolution of objects which exhibit radial motion relative to an observing sensor. When applied to rotating objects, Doppler processing yields resolution in cross-range along an axis normal to both object rotation and line-of-sight axes. In this case, the cross-range resolution performance is dictated by the angular interval over which the data are observed and processed. This paper treats a tomographic extension of Doppler processing in the case of a rotating object (or a rotating planar array of point scatterers). It uses a stationary, continuous-wave (CW) irradiating source and sensor, co-located in the plane being imaged. The processing of data from a rotating object is shown to be equivalent to synthesizing an aperture which is a segment of a circle, however, processing over large angular rotations requires a focusing correction. Angular rotations up to and including 2? radians are considered. For this latter condition the system simulates an annular aperture which encloses the object. With this technique, high resolution may be obtained in all directions in the object plane without the use of a wideband signal, and equal point-objects separated by a quarter wavelength may be resolved. The imaging process provides high resolution for sparse arrays of objects of similar strength which are small in comparison to a wavelength. The imaging capability in the case of dense object arrays or large objects is limited and has a restricted dynamic range.
Incorporation of fixed speed wind farms in power flow analysis

The steady state behaviour of a power system is usually determined through power flow analysis. This paper proposes a simple method of incorporating the model of a squirrel-cage induction generator used in a fixed speed wind farm into conventional power flow programs to evaluate the steady state results. All parameters of exact equivalent circuit of the generator are carefully incorporated into input data file of the program. Unlike previous methods, no modification to source codes of the program or computational algorithm is required. The proposed method is then tested on a simple radial system and a 5-bus meshed system.
Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

Recurrent chromosomal rearrangements are common in cancer cells and may be influenced by nonrandom positioning of recombination-prone genetic loci in the nucleus. However, the mechanism responsible for spatial proximity of specific loci is unknown. In this study, we use an 18 Mb region on 10q11.2-21 containing the RET gene and its recombination partners, the H4 and NCOA4 (ELE1) genes, as a model chromosomal region frequently involved in RET/PTC rearrangements in thyroid cancer. RET/PTC is particularly common in tumors from children exposed to ionizing radiation. Using fluorescence in situ hybridization and three-dimensional microscopy, the locations of five different loci in this region were mapped in interphase nuclei of normal human thyroid cells. We show that RET and NCOA4 are much closer to each other than expected based on their genomic separation. Modeling of chromosome folding in this region suggests the presence of chromosome coiling with coils of approximately 8 Mb in length, which positions the RET gene close to both, the NCOA4 and H4, loci. There was no significant variation in gene proximity between adult and pediatric thyroid cells. This study provides evidence for large-scale chromosome folding of the 10q11.2-21 region that offers a structural basis for nonrandom positioning and spatial proximity of potentially recombinogenic intrachromosomal loci.
AN INTEGRATED FORMULATION FOR SELECTING THE MOST PROBABLE MULTINOMIAL CELL

We refer to the two classical approaches to multinomial selection as the indifference zone approach and the subset selection approach. This paper integrates these two approaches by separating the parameter space into two disjoint subspaces: the preference zone (PZ) and the indifference zone (IZ). In the PZ we insist on selecting the best (most probable) cell for a correct selection (CS 1) but in the IZ we define any selected subset to be correct (CS 2) if it contains the best cell. We then propose a single stage procedure R to achieve the selection goals CS 1 and CS 2 simultaneously with certain probability requirements. It is shown that both the probability of a correct selection under IZ, P(CS 2 |PZ), and the probability of a correct selection under IZ, P(CS 2 |IZ), satisfy some monotonicity properties and the least favorable configuration in PZ and the worst configuration in IZ can be found by these properties.
Qualitative and quantitative cancer risk assessment of 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin (2, 3, 7, 8-TCDD)

Abstract The carcinogenicity of 2,3,7,8-TCDD at multiple organ sites in animals has been well established by several cancer bioassays. Results of two of the most notable of these, the Kociba et al. (1978) rat feeding study and the National Toxicology Program (1980) gavage study in rats and mice showed hepatocellular carcinomas in two strains of female rats and male and female mice. Other tumor sites included carcinomas of the lung, tongue, hard palate and nasal turbinates, thyroid, and subcutaneous tissue. The evidence for carcinogenicity of 2,3,7,8-TCDD in animals is regarded as “sufficient” using the classification system of the International Agency for Research on Cancer (IARC). Two Swedish epidemiologic case-control studies (Hardell and Sandstrom, 1979; Eriksson et al. 1979, 1981) reported a significant five- to sevenfold excess risk of soft-tissue sarcomas (STS) from occupational exposure to chlorinated phenoxyacetic acid herbicides and/or chlorophenols. Additionally, several small cohort studies collectively exhibited an unusual cluster of STS, significantly increased over combined expected incidence. Problems with these studies do not appear to be sufficient to discount this excess risk. The human evidence alone for the carcinogenicity of 2,3,7,8-TCDD is “inadequate” using the IARC classification. However, for 2,3,7,8-TCDD in combination with chlorinated phenoxyacetic acid herbicides and/or chlorophenols, the human evidence is considered to be “limited.” The overall evidence for carcinogenicity considering both animal and human studies would place 2,3,7,8-TCDD alone in the IARC category 2B, meaning that the substance is probably carcinogenic in humans. The overall weight of evidence for 2,3,7,8-TCDD in combination with chlorinated phenoxyacetic acid herbicides and/or chlorophenols is regarded as IARC category 2A, also meaning that they are probably carcinogenic for humans. Using current EPA methodology for quantitatively estimating cancer risks, several animal data sets have been analyzed. Comparing the results, the upper-limit incremental unit risk estimate is 1.6 × 10−2 for a lifetime exposure of 1 ng/kg/day. This estimate is derived from a lifetime feeding study (Kociba et al., 1978) in which 2,3,7,8-TCDD induced tumors of the liver, lungs, hard palate, and nasal turbinates in female rats. Incremental unit cancer risks are also extrapolated for lifetime 2,3,7,8-TCDD exposures in water and air. Based on continuous lifetime exposure to 1 ng/L 2,3,7,8-TCDD in drinking water, the upper-limit estimate of extra cancer risk per individual is 4.5 × 10−3. For lifetime exposure to 1 pg 2,3,7,8-TCDD/m3 in the ambient air, the upper-limit individual risk is 3.3 × 10−5.
Prolonged Survival of a Patient With Left Ventricular Pseudoaneurysm Following Myocardial Infarction and Mitral Valve Replacement

We present the case of a patient with left ventricular pseudoaneurysm following acute myocardial infarction. Survival for 2 years following diagnosis, despite the large size of the aneurysm, and subsequent management with cardiac transplantation represent unusual and interesting aspects of this complication of myocardial infarction.
Towards climate justice: how do the most vulnerable weigh environment-economy trade-offs?

Abstract The world’s poor are especially vulnerable to environmental disasters, including the adverse consequences of climate change. This creates a challenge for climate justice advocates who seek to ensure that those least responsible for causing climate change do not bear unwanted burdens of mitigation. One way to promote climate justice could be to pay particular attention to the environmental policy preferences of citizens from poorer, lower-emitting countries. This paper examines opinions on environment–economy trade-offs and willingness to make personal financial contributions to protect the environment among residents of 42 developed and developing countries using data from the 2005–2008 World Values Survey, the 2010 Climate Risk Index, and World Bank development indicators. Results reveal that individuals in developing countries are less likely to support policies to prioritize environmental protection over economic growth but are more willing to donate personal income for pro-environmental efforts compared to citizens of more developed nations.
Venlafaxine in treatment-resistant obsessive-compulsive disorder.

Background While selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of obsessive-compulsive disorder (OCD), approximately 40% of patients fail to respond to SSRIs. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that might be effective in the treatment of OCD, even among those who have failed previous SSRI trials. Method Thirty-nine patients who met DSM-IV criteria for OCD, including 29 who were resistant to prior SRI treatment trials, were treated with venlafaxine in an open, naturalistic fashion. Improvement was assessed using the Clinical Global Impressions-Improvement scale. Results Of 39 patients treated with venlafaxine, 27 (69.2%) were rated as sustained treatment responders. Of the 29 patients who did not respond to 1 or more previous SRI trials, 22 (75.9%) were rated as having sustained response to treatment. Mean dose of venlafaxine was 232.2 mg/day (range, 37.5-375 mg/day), and it was generally well tolerated. Conclusion Venlafaxine may be beneficial to individuals with OCD, including those who have not responded to prior SSRI trials. However, these findings must be interpreted with caution, as the study is limited by its open, retrospective nature and its inclusion of patients with comorbid diagnoses and patients on concomitant medications. Prospective, controlled trials with a more homogeneous patient population are needed to replicate these preliminary findings.
Hypothermia inhibits human E-selectin transcription.

During endothelial cell activation, the formation and expression of E-selectin require transcriptional activation of the E-selectin gene, mediated by the coordinated action of several transcription factors and cis-acting elements in its 5'-flanking region. It is reported that in vitro hypothermia (25 degrees C) transiently inhibits transcriptional activation and surface expression of E-selectin as well as neutrophil adherence to cultured human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), interleukin-1 (IL-1), or tumor necrosis factor (TNF). Rewarming HUVECs treated with LPS, IL-1, or TNF to 37 degrees C restores E-selectin transcript accumulation, E-selectin surface expression, and neutrophil adherence to HUVECs at levels equivalent to similarly treated HUVECs maintained at 37 degrees C continuously. Despite the absence of detectable E-selectin transcription at 25 degrees C, activation of the transcription factor NF-kappaB still occurred in HUVECs treated with LPS, IL-1, or TNF, indicating that signal transduction was not blocked by hypothermia. It is concluded that neutrophil adherence to activated endothelium mediated by E-selectin is reversibly inhibited by hypothermia. The protective effect of hypothermia clinically (e.g., cardiopulmonary bypass) may, in part, be mediated by transiently inhibiting the expression of an endothelial cell activation phenotype.
Supersymmetric regulators and supercurrent anomalies

Abstract The supercurrent anomalies of the supercurrent S μ of the supersymmetric Yang-Mills theory in Wess-Zumino gauge are computed using the supersymmetric dimensional regulator of Siegel. It is shown that γ μ S μ =0 and ∂ μ S μ ≠0 in agreement with an earlier calculation based on the Adler-Rosenberg method. The problem of exhibiting the chiral anomaly and a regulator for local supersymmetry suggests that the interpretation of dimensional reduction in component language is incomplete.
To Die in This Way: Nicaraguan Indians and the Myth of Mestizaje, 1880-1965

To Die In This Way: Nicaraguan Indians and the Myth of Mestizaje, 1880-1965. Jeffrey L. Gould. Durham, NC: Duke University Press, 1998. xiv. 305 pp., bibliography, Index.
Perceptions Regarding the IFSP Process in a Statewide Interagency Service Coordination Program

Development of an Individualized Family Service Plan (IFSP) for children receiving Part H services is an integral part of North Carolina's interagency Child Service Coordination Program. Perceptions of the IFSP process were assessed in a statewide survey of child service coordinators. Divergent viewpoints about the usefulness and process of developing the IFSP emerged, depending on the program with which the child service coordinator worked. These findings have implications for training professionals about the IFSP process in the context of strengthening the implementation of interagency, comprehensive service coordination programs.
The Efflux Pump Inhibitor Timcodar Improves the Potency of Antimycobacterial Agents

Previous studies indicated that inhibition of efflux pumps augments tuberculosis therapy. In this study, we used timcodar (formerly VX-853) to determine if this efflux pump inhibitor could increase the potency of antituberculosis (anti-TB) drugs against Mycobacterium tuberculosis in in vitro and in vivo combination studies. When used alone, timcodar weakly inhibited M. tuberculosis growth in broth culture (MIC, 19 μg/ml); however, it demonstrated synergism in drug combination studies with rifampin, bedaquiline, and clofazimine but not with other anti-TB agents. When M. tuberculosis was cultured in host macrophage cells, timcodar had about a 10-fold increase (50% inhibitory concentration, 1.9 μg/ml) in the growth inhibition of M. tuberculosis and demonstrated synergy with rifampin, moxifloxacin, and bedaquiline. In a mouse model of tuberculosis lung infection, timcodar potentiated the efficacies of rifampin and isoniazid, conferring 1.0 and 0.4 log10 reductions in bacterial burden in lung, respectively, compared to the efficacy of each drug alone. Furthermore, timcodar reduced the likelihood of a relapse infection when evaluated in a mouse model of long-term, chronic infection with treatment with a combination of rifampin, isoniazid, and timcodar. Although timcodar had no effect on the pharmacokinetics of rifampin in plasma and lung, it did increase the plasma exposure of bedaquiline. These data suggest that the antimycobacterial drug-potentiating activity of timcodar is complex and drug dependent and involves both bacterial and host-targeted mechanisms. Further study of the improvement of the potency of antimycobacterial drugs and drug candidates when used in combination with timcodar is warranted.
The Relationship of the 6-Min Walk Test to Maximal Oxygen Consumption in Transplant Candidates With End-Stage Lung Disease

Study objective To assess the relationship of distance ambulated during the 6-min walk test (6'WT) to maximal oxygen consumption (VO2 max). Design Multivariate analysis of patient characteristics to VO2 max. Setting Pre-lung transplant evaluation. Patients 60 patients (22 men, 38 women; mean age, 44 years) with end-stage lung disease (mean FEV1 and forced vital capacity of 0.97 and 1.93, respectively). Measurements and results The 6'WT was performed on a level hallway surface, and VO2 max was obtained during maximal cycle ergometry exercise testing with respiratory gas analysis. Multivariate analysis of patient characteristics (age, sex, weight, FEV1, FVC, diffusing capacity for carbon monoxide (DCO), 6'WT distance ambulated, number of rests per 6'WT, and the maximal heart rate, blood pressure, rate-pressure product, respiratory rate, oxygen saturation, rating of perceived exertion, and amount of supplemental oxygen used during the 6'WT) was performed on two groups of 30 patients each (group A or B) who were randomly assigned to either group by a process of random selection using a computer-generated random numbers program. Distance ambulated was the strongest independent predictor of VO2 max (r = 0.73; p Conclusions The distance ambulated during a 6'WT can predict VO2 max in patients with end-stage lung disease. The addition of several patient characteristics can increase the ability to predict VO2 max and account for more of the variability. Such information is valuable when assessing patient response to therapeutic intervention if respiratory gas analysis is unavailable or impractical.
Physiologic hyperinsulinemia enhances counterregulatory hormone responses to hypoglycemia in IDDM.

We evaluated the effect of physiologic hyperinsulinemia (plasma insulin 329 +/- 62 vs 687 +/- 62 pmol/L) on counterregulatory hormone responses in 8 IDDM subjects studied during a 2-hour hypoglycemic clamp study with an equivalent degree of hypoglycemia (plasma glucose 3.1 +/- 0.1 and 3.0 +/- 0.1 mmol/L, respectively). Plasma epinephrine levels were increased by 71% during the last 60 minutes of hypoglycemia in the high insulin study (840 +/- 180 vs 1440 +/- 310 pmol/L, respectively p = 0.006). In addition, plasma cortisol and norepinephrine were also increased in the high insulin study (by 19% and 24% respectively, p < 0.01, for both). Plasma growth hormone and glucagon concentrations were not altered by high dose insulin infusion. In spite of increased epinephrine secretion, the glucose infusion rate required to maintain glucose was 2-fold greater in the high insulin study, and there was greater suppression of lipolysis in that group. We conclude that hyperinsulinemia may enhance counterregulatory hormo...
Tectonic assembly of the Brevard-Chauga belt, South Carolina: Fluid inclusion evidence from Appalachian Deep Core Site Investigation Hole 2 (ADCOH-2)

Abstract Appalachian Deep Core Hole 2 (ADCOH-2) penetrated part of one of the most persistent and important tectonostratigraphic belts in the southern Appalachians—the Brevard-Chauga belt in South Carolina. The Brevard-Chauga belt is a subdivision of the Inner Piedmont and it includes the Brevard fault zone. The 307 m core contains four imbricated slices of Early Ordovician Henderson Gneiss and metasedimentary rocks of the Chauga River Formation. Aqueous (NaCl–CaCl 2 ) inclusions and CO 2 –CH 4 -rich inclusions present in syntectonic quartz veins in the metasedimentary units, together with garnet-biotite geothermometry, provide information on the P-T conditions during uplift. Garnet-biotite geothermometry in the Brevard metasiltstone indicates a crystallization temperature of 466±52 °C, which together with published 40 Ar/ 39 Ar hornblende data from the Chauga belt, are interpreted as a Neoacadian (late Devonian) garnet crystallization age. High-density CO 2 -rich fluid inclusion isochores indicate a pressure of ∼4.5 kbar at 466±52 °C at this time. A Rb–Sr muscovite model age of 302 Ma in retrograde mylonitic Henderson Gneiss is interpreted as an Alleghanian recrystallization age. Fluid inclusions record a 2.5 kbar decompression event at this time, consistent with thrust assembly of the tectonostratigraphic units in the core.
Dyon Three-Triplet Model of Hadrons

Schwinger's composite model of hadrons, based on dyons, is formulated as a dyon three-triplet model with the postulated symmetry group SU(3)[electric] \ensuremath{\bigotimes} SU(3)[magnetic]. The hadron spectrum is dominated by the superstrong magnetic-charge exchange forces; we find the first "exotic" states to be in the meson channel of the ($2D2\overline{D}$) system. This model possesses the good features of the quark model and explains its paradoxes.
Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders.

Abstract Background Quinolone antibiotics are associated with increased risk of tendinopathy. Identifying at-risk individuals has important clinical implications. We examined whether age, sex, glucocorticoid use, obesity, diabetes, and renal failure/dialysis predispose individuals to the adverse effects of quinolones. Methods Among 6.4 million patients in The Health Improvement Network (THIN) database, 28,907 cases of Achilles tendonitis and 7685 cases of tendon rupture were identified in a case-crossover study. For each participant, we ascertained whether there was a prescription of a quinolone and comparison antibiotic within 30 days before the diagnosis of tendon disorder (case period) and a prescription of the same medications within 30 days 1 year before disease diagnosis (control period). Results Use of quinolones was strongly associated with an increased risk of Achilles tendonitis (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.7) and tendon rupture (OR, 2.0; 95% CI, 1.2-3.3). No association was found between the use of other antibiotics and either outcome. The association with Achilles tendonitis was stronger among participants who were aged more than 60 years (OR, 8.3 vs 1.6), who were nonobese (OR, 7.7 vs 2.4), and who used oral glucocorticoids (OR, 9.1 vs 3.2). The association was nonsignificantly stronger in women (OR, 5.0 vs 3.6), diabetic persons (OR, 7.0 vs 4.1), and those in renal failure or receiving dialysis (OR, 20.0 vs 3.9). The effect for tendon rupture was stronger in women, with borderline significance in glucocorticoid users and nonobese persons. Conclusion Quinolone-associated tendinopathy is more pronounced among elderly persons, nonobese persons, and individuals with concurrent use of glucocorticoids.
Short communication: A new chi-square approximation to the distribution of non-negative definite quadratic forms in non-central normal variables

This note proposes a new chi-square approximation to the distribution of non-negative definite quadratic forms in non-central normal variables. The unknown parameters are determined by the first four cumulants of the quadratic forms. The proposed method is compared with Pearson's three-moment central @g^2 approximation approach, by means of numerical examples. Our method yields a better approximation to the distribution of the non-central quadratic forms than Pearson's method, particularly in the upper tail of the quadratic form, the tail most often needed in practical work.
907 MUMPS VIRUS INDUCED DIABETES MELLITUS IN A RODENT MODEL

Mumps virus have been postulated in the etiology of diabetes mellitus. The following experiments were to delineate the relationship between mumps virus infection and diabetes in a rodent model. Adult Wistar rats were inoculated intraperitoneally with a laboratory adapted strain of mumps virus. Control animals were injected with a similar volume of spent tissue culture media. Standard glucose tolerance tests were performed on all animals at the onset of experiments and regular intervals thereafter. The rodents were maintained in seperate facilities and tested periodically for hyperglycemia and glucosuria. In addition, on a weekly basis infected and control animals were sacrificed and pancreatic tissues examined. Two weeks after inoculation with mumps virus 17 of 20 rats demonstrated abnormal glucose tolerance curves which persisted 4-6 weeks. Insulin secretion, temperature elevation, appetite and activity did not differ in the two groups. Histological specimens revealed ablation of beta cell components in the pancreas of mumps virus inoculated rodents. Mumps virus was not recovered from any of the animals. Mumps virus may be a diabetogenic agent in the rodent model. The mechanism of this action is postulated to be selective destruction of pancreatic beta cells. However, the production of ineffective insulin cannot yet be ruled out.
Peroxidase-mediated in vitro metabolism of diethylstilbestrol and structural analogs with different biological activities.

Summary The comparative peroxidative metabolism of diethylstilbestrol (DES) and structurally related compounds of different biological activity was investigated in vitro with horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ) as a model peroxidase system: UV spectroscopy revealed the formation of p -quinone intermediates in HRP-H 2 O 2 catalyzed incubations of DES, 3′,3″,5′,5″-tetrafluoro-DES (TF-DES) and dimethylstilbestrol (DMS) and the tautomerization of the quinones to their dien compounds, Z,Z -dienestrol ( Z,Z -DIES), tetrafluoro-dienestrol (TF-DIES) and dienmestrol (DIMS) respectively, which were characterized by HPLC and GC/MS. Z,Z -DIES, E,E -DIES, TF-DIES and DIMS were subject to further peroxidative metabolism; however, quinone intermediates were not formed in the HRP-H 2 O 2 containing incubations according to UV spectroscopy. Similarly, hexestrol (HES), 4′- O -methyl-DES (M-DES) and 4′,4″- O -dimethyl-DES (DM-DES) did not form quinone intermediates; moreover, they showed little or no apparent metabolic conversion under conditions where DES, TF-DES and DMS were readily peroxidized. However, at a 20-fold higher peroxidase concentration HES and M-DES showed metabolic conversion whereas DM-DES did not. It is proposed that the compounds studied with HRP-H 2 O 2 in vitro are metabolized to different extents via phenoxy free radicals and quinone intermediates, both of which are reactive metabolites. These results should help us to understand the toxic effects of DES analogs in various biological systems in which peroxidative metabolism is operative, e.g. in the female genital tract and in SHE-cells.
Hemodynamic and exercise performance with pulsatile and continuous-flow left ventricular assist devices.

Background— Continuous-flow rotary pumps with axial design are increasingly used for left ventricular assist support. The efficacy of this design compared with pulsatile, volume displacement pumps, with respect to characteristics of left ventricular unloading, and exercise performance remains largely unstudied. Methods and Results— Thirty-four patients undergoing implantation with a pulsatile, volume displacement pump operating in a full-to-empty cycle (HeartMate XVE; Thoratec Inc, Pleasanton, Calif; n=16) or continuous-flow rotary pump with an axial design operating at a fixed rotor speed (HeartMate II; Thoratec Inc; n=18) were evaluated with right heart catheterization and echocardiography preoperatively and at 3 months postoperatively and cardiopulmonary exercise testing 3 months postoperatively. Support with either the XVE or II resulted in significant ( P 2 −XVE: 46.8±10.2 versus II: 49.1±13.6). Echocardiography at 3 months demonstrated a significantly ( P Conclusions— The HeartMate XVE or II provided equivalent degrees of hemodynamic support and exercise capacity. The XVE was associated with greater left ventricular volume unloading. Characteristics of left ventricular pressure and volume unloading between these pump designs and mode of operation do not influence early exercise performance.
Electro-Optical Properties of Colloids

This paper deals with investigations of the electric birefringence of colloidal solutions in alternating fields; the most detailed measurements were carried out with monodisperse bentonite sols. In general the double refraction consists of a direct and an alternating part, both of which depend on field strength and frequency of the applied field, particle size, temperature, and concentration of the solution. The direct birefringence, which can be positive or negative, can reverse its sign with a change of any of the five parameters mentioned. The measurements are interpreted by means of a relaxation theory which can explain all phenomena connected with the vibrating component in a satisfactory way. Likewise this theory is capable of explaining the variations and the reversal of the direct birefringence with changes of the frequency, field strength, particle size, and temperature. The character of the dependence of the steady birefringence on concentration which has not hitherto been observed with other colloids was first discussed by H. Mueller. The changes and reversal of sign of the direct component with concentration are accounted for by the assumption that the micelles are surrounded by a compressed water hull; the pressure of the water hull depends on particle size and concentration. Direct and alternating birefringence have different relaxation times.
Rabbit Anti-HIV-1 Monoclonal Antibodies Raised by Immunization Can Mimic the Antigen-Binding Modes of Antibodies Derived from HIV-1-Infected Humans

The rabbit is a commonly used animal model in studying antibody responses in HIV/AIDS vaccine development. However, no rabbit monoclonal antibodies (MAbs) have been developed previously to study the epitope-specific antibody responses against HIV-1 envelope (Env) glycoproteins, and little is known about how the rabbit immune system can mimic the human immune system in eliciting such antibodies. Here we present structural analyses of two rabbit MAbs, R56 and R20, against the third variable region (V3) of HIV-1 gp120. R56 recognizes the well-studied immunogenic region in the V3 crown, while R20 targets a less-studied region at the C terminus of V3. By comparison of the Fab/epitope complex structures of these two antibodies raised by immunization with that of the corresponding human antibodies derived from patients chronically infected with HIV-1, we found that rabbit antibodies can recognize immunogenic regions of gp120 and mimic the binding modes of human antibodies. This result can provide new insight into the use of the rabbit as an animal model in AIDS vaccine development.
End-stage renal disease in two pediatric patients with Fechtner syndrome

Fechtner syndrome, a disease in the spectrum of the hereditary nephridites, is a macrothrombocytopenia associated with sensorineural hearing loss, cataracts, nephritis, and characteristic leukocyte inclusions. Renal biopsy findings are consistent with those of Alport syndrome, and the associated renal disease is said to be unusual before mid to late adulthood. Here, we review the available literature on this disease and report two African-American pediatric patients with Fechtner syndrome who rapidly progressed to end-stage renal disease during adolescence. We conclude that chronic renal failure can occur at a young age in patients with Fechtner syndrome, with a possible relation to race/ethnicity. Fechtner syndrome, or other variants of Alport syndrome, need to be considered in patients presenting with proteinuria and thrombocytopenia.
A simple linear relationship and definition of a unit for proteinase activity

Abstract A mathematical transformation involving the 3 2 power of the number of milligrams of soluble nitrogen released from the substrate makes possible the expression of proteolytic activity in terms of the quantity of enzyme required to cause a given change in the substrate. The relationship is linear for several different enzymes including papain, patent flour, malted barley, malted wheat flour, and several fungal preparations acting on either Bacto-hemoglobin or gluten substrate. One unit of proteinase activity is defined as that activity contained by a quantity of enzyme-active material which gives an increase in soluble nitrogen in a 10-ml. aliquot from the filtrate corresponding to the intersection of the straight line with the transformed value representing 1 ml. of 0.0714 N alkali. This method of expressing proteolytic activity greatly simplifies the expression of proteolytic activity and has been found convenient for analytical purposes as well as for comparing activities of different enzymes acting on the same substrate.
On the generation of secondary motion in circular to rectangular transition ducts

A computer code has been developed for the calculation of three-dimensional turbulent flow in circular to rectangular transition ducts. The governing equations are written in a general curvilinear coordinate system so that all singly-connected geometrical configurations can be accommodated. Turbulence closure is through the standard k-epsilon model or a Reynolds stress closure model. Computed results show qualitative agreement with experimental data. Pressure-induced secondary flow is the dominant mode through the transition, but turbulence-induced secondary flow becomes prominent some distance downstream of the transition.