Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of a1-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal (»75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 µM), prostaglandin F2a (PGF2a; 1 µM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 µM and 500 µM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 ± 6% (N = 26 rings) to 57 ± 7% (N = 26 rings) and 34.9 ± 6% (N = 13 rings), respectively (P<0.05), and for PGF2a from a control response of 75 ± 10% (N = 16 rings) to 52 ± 8% (N = 19 rings) and 25.9 ± 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 µM and 500 µM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 ± 5.0% for the control response (N = 38 rings), 59 ± 6.0% in the presence of 200 µM heptanol (N = 17 rings), and 70 ± 6.0% in the presence of 500 µM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 ± 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.

Simulation of the Interaction Mean Free Path between Neutrons and TRISO Particles

The interaction mean free path between neutrons and TRISO particles is simulated using scripts written in MATLAB to solve the increasing error present with an increase in the packing factor in the reactor physics code Serpent. Their movement is tracked both in an unbounded and in a bounded space. Their track is calculated, depending on the program, linearly directly using the position vectors of the neutrons and the surface equations of all the fuel particles; by dividing the space in multiple subspaces, each of which contain a fraction of the total number of particles, and choosing the particles from those subspaces through which the neutron passes through; or by choosing the particles that lie within an infinite cylinder formed on the movement axis of the neutron. The estimate from the current analytical model, based on an exponential distribution, for the mean free path, utilized by Serpent, is used as a reference result. The results from the implicit model in Serpent imply a too long mean free path with high packing factors. The received results support this observation by producing, with a packing factor of 17 %, approximately 2.46 % shorter mean free path compared to the reference model. This is supported by the packing factor experienced by the neutron, the simulation of which resulted in a 17.29 % packing factor. It was also observed that the neutrons leaving from the surfaces of the fuel particles, in contrast to those starting inside the moderator, do not follow the exponential distribution. The current model, as it is, is thus not valid in the determination of the free path lengths of the neutrons.

Phagocytosis by macrophages mediated by receptors for denatured proteins - dependence on tyrosine protein kinases

Previous studies have demonstrated that some components of the leukocyte cell membrane, CR3 (Mac-1, CD11b/CD18) and p150/95, are able to bind to denatured proteins. Thus, it is of interest to know which effector functions of these cells can be triggered by these receptors when they interact with particles or surfaces covered with denatured proteins. In the present study we analyzed their possible role as mediators of phagocytosis of red cells covered with denatured bovine serum albumin (BSA) by mouse peritoneal macrophages. We observed that a) macrophages are able to recognize (bind to) these red cells, b) this interaction can be inhibited by denatured BSA in the fluid phase, c) there is no phagocytosis of these particles by normal macrophages, d) phagocytosis mediated by denatured BSA can be, however, effectively triggered in inflammatory macrophages induced by glycogen or in macrophages activated in vivo with LPS, and e) this phagocytic capacity is strongly dependent on the activity of tyrosine protein kinases in its signal transduction pathway, as demonstrated by using three kinds of enzyme inhibitors (genistein, quercetin and herbimycin A).

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3%) and ADH1C*1 (62.5%) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5%, N = 201 and 85 vs 94.5 and 40.7%, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.

Caspase dependence of the death of neonatal retinal ganglion cells induced by axon damage and induction of autophagy as a survival mechanism

We examined the degeneration of post-mitotic ganglion cells in ex-vivo neonatal retinal explants following axon damage. Ultrastructural features of both apoptosis and autophagy were detected. Degenerating cells reacted with antibodies specific for activated caspase-3 or -9, consistent with the presence of caspase activity. Furthermore, peptidic inhibitors of caspase-9, -6 or -3 prevented cell death (100 µM Ac-LEDH-CHO, 50 µM Ac-VEID-CHO and 10 µM Z-DEVD-fmk, respectively). Interestingly, inhibition of autophagy by 7-10 mM 3-methyl-adenine increased the rate of cell death. Immunohistochemistry data, caspase activation and caspase inhibition data suggest that axotomy of neonatal retinal ganglion cells triggers the intrinsic apoptotic pathway, which, in turn, is counteracted by a pro-survival autophagic response, demonstrated by electron microscopy profiles and pharmacological autophagy inhibitor.

Personality traits and psychiatric comorbidities in alcohol dependence

Non-adaptive personality traits may constitute risk factors for development of psychiatric disorders such as depression and anxiety. We aim to evaluate associations and the predictive value of personality traits among alcohol-dependent individuals, with or without psychiatric comorbidities. The convenience sample comprised two groups of males over 18 years of age: one with subjects who had an alcohol dependence diagnosis (AG, n=110), and a control group without abuse and/or alcohol dependence diagnosis (CG, n=110). The groups were assessed by means of the Structured Clinical Interview DSM-IV (SCID-IV). AG participants were recruited among outpatients from the university hospital, whereas CG participants were recruited from a primary healthcare program. Data collection was done individually with self-assessment instruments. Parametric statistics were performed, and a significance level of P=0.05 was adopted. A positive correlation was observed between openness and the length of time that alcohol has been consumed, as were significant and negative correlations between conscientiousness and both the length of time alcohol has been consumed and the number of doses. For alcoholics, extraversion emerged as a protective factor against depression development (P=0.008) and tobacco abuse (P=0.007), whereas openness worked as a protective factor against anxiety (P=0.02). The findings point to specific deficits presented by alcoholics in relation to personality traits with or without psychiatric comorbidities and to the understanding that therapeutic approaches should favor procedures and/or preventive measures that allow more refined awareness about the disorder.

Path Analysis of Online Users Using Clickstream Da-ta: Case Online Magazine Website

This paper explores behavioral patterns of web users on an online magazine web-site. The goal of the study is to first find and visualize user paths within the data generated during collection, and to identify some generic behavioral typologies of user behavior. To form a theoretical foundation for processing data and identifying behavioral ar-chetypes, the study relies on established consumer behavior literature to propose typologies of behavior. For data processing, the study utilizes methodologies of ap-plied cluster analysis and sequential path analysis. Utilizing a dataset of click stream data generated from the real-life clicks of 250 ran-domly selected website visitors over a period of six weeks. Based on the data collect-ed, an exploratory method is followed in order to find and visualize generally occur-ring paths of users on the website. Six distinct behavioral typologies were recog-nized, with the dominant user consuming mainly blog content, as opposed to editori-al content. Most importantly, it was observed that approximately 80% of clicks were of the blog content category, meaning that the majority of web traffic occurring in the site takes place in content other than the desired editorial content pages. The out-come of the study is a set of managerial recommendations for each identified behavioral archetype.

The Path of Possibilities

by Ilan Averbuch presented to Brock in 1988.

Mackenzie Chown Path

Path running next to the Mackenzie Chown Complex.

Mackenzie Chown Path

View of the Complex and the path running along it from the east.

On the path integral formulation and the evaluation of quantum statistical averages

Four problems of physical interest have been solved in this thesis using the path integral formalism. Using the trigonometric expansion method of Burton and de Borde (1955), we found the kernel for two interacting one dimensional oscillators• The result is the same as one would obtain using a normal coordinate transformation, We next introduced the method of Papadopolous (1969), which is a systematic perturbation type method specifically geared to finding the partition function Z, or equivalently, the Helmholtz free energy F, of a system of interacting oscillators. We applied this method to the next three problems considered• First, by summing the perturbation expansion, we found F for a system of N interacting Einstein oscillators^ The result obtained is the same as the usual result obtained by Shukla and Muller (1972) • Next, we found F to 0(Xi)f where A is the usual Tan Hove ordering parameter* The results obtained are the same as those of Shukla and Oowley (1971), who have used a diagrammatic procedure, and did the necessary sums in Fourier space* We performed the work in temperature space• Finally, slightly modifying the method of Papadopolous, we found the finite temperature expressions for the Debyecaller factor in Bravais lattices, to 0(AZ) and u(/K/ j,where K is the scattering vector* The high temperature limit of the expressions obtained here, are in complete agreement with the classical results of Maradudin and Flinn (1963) .

Pressure dependence of spin fluctuations in metallic glasses Zrâ â Niâ â ,Zrâ â (Nix/Feâ â â -x)â â and /Zrx/feâ â â -x

The superconducting transition temperature Tc of metallic glasses ZrxFelOO-x (x=80, 75), Zr75(NixFelOO-x)25 (x=75, 50, 25), and CU2SZr75 were measured under quasi-hydrostatic pressure up to 8 OPa (80kbar). The volume (pressure) dependence of the electron-phonon coupling parameters Aep for CU25Zr75 was calculated using the McMillan equatio11. Using this volume dependence of Aep and the modified McMillan equation which incorporates spin-fluctuations, the volume dependence of the spin fluctuation parameter, Asf, was determined in Zr75Ni25, ZrxFelOO-x , a11d Zr75(NixFelOO-x)25. It was found that with increasing pressure, spinfluctuations are suppressed at a faster rate in ZrxFe lOO-x and Zr75(NixFelOO-x)25, as Fe concentration is increased. The rate of suppression of spin-fluctuations with pressure was also found to be higher in Fe-Zr glasses than in Ni-Zr glasses of similar composition.

Pressure dependence of superconducting properties of MgB2 /

We prepared samples of MgB2 and ran sets of experiments aimed for investigation of superconducting properties under pressure. We found the value of pressure derivative of the transition temperature -1.2 ± 0.05 K/GPa. Then, using McMillan formula, we found that the main contribution to the change of the transition temperature under the pressure is due to the change in phonon frequencies. Griineisen parameter was calculated to be 7g = 2.4. Our results suggest that MgB2 is a conventional superconductor.

The design of a reflectance spectrometer and its calibration using SrTiO3 /

A new Ultra-High Vacuum (UHV) reflectance spectrometer was successfully designed, making use of a Janis Industries ST-400 sample cryostat, IR Labs bolometer, and Briiker IFS 66 v/S spectrometer. Two of the noteworthy features include an in situ gold evaporator and internal reference path, both of which allow for the experiment to progress with a completely undisturbed sample position. As tested, the system was designed to operate between 4.2 K and 325 K over a frequency range of 60 - 670 cm~^. This frequency range can easily be extended through the addition of appUcable detectors. Tests were performed on SrTiOa, a highly ionic incipient ferroelectric insulator with a well known reflectance. The presence and temperatmre dependence of the lowest frequency "soft" mode were measured, as was the presence of the other two infrared modes. During the structural phase transition from cubic to tetragonal perovskite, the splitting of the second phonon mode was also observed. All of the collected data indicate good agreement with previous measurements, with a minor discrepency between the actual and recorded sample temperatures.