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Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today’s technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with special importance in reproductive and developmental processes. PACAP is found in two bioactive forms: PACAP27 and PACAP38. Recently, we have described that PACAP38 is present in high levels in the milk of human and ruminant animals. Breastfeeding is of utmost importance in proper nutrition of the newborn, but artificial nursing with infant formulas is necessary when breastfeeding is not available. Composition of the breast milk varies during the whole period of nursing and it shows differences at the beginning (foremilk) and the end of an actual suckling (hindmilk). The aim of this study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in different milk and infant formula samples by radioimmunoassay and to prove the presence of PACAP38 in the infant formula by mass spectrometry. We found similar PACAP38-LI in human mature foremilk and hindmilk samples, in the fresh and pasteurized cow milk and also in formulas. However, we found significantly higher PACAP38-LI in the hypoantigenic formula undergoing extensive hydrolysis compared to the non-hypoantigenic ones. Our results suggest that PACAP38 is relatively stable in the milk and it can withstand the manufacturing processes.

ARGOS, the laser-guided adaptive optics system for the Large Binocular Telescope (LBT), is now under construction at the telescope. By correcting atmospheric turbulence close to the telescope, the system is designed to deliver high resolution near infrared images over a field of 4 arc minute diameter. Each side of the LBT is being equipped with three Rayleigh laser guide stars derived from six 18 W pulsed green lasers and projected into two triangular constellations matching the size of the corrected field. The returning light is to be detected by wavefront sensors that are range gated within the seeing-limited depth of focus of the telescope. Wavefront correction will be introduced by the telescope's deformable secondary mirrors driven on the basis of the average wavefront errors computed from the respective guide star constellation. Measured atmospheric turbulence profiles from the site lead us to expect that by compensating the ground-layer turbulence, ARGOS will deliver median image quality of about 0.2 arc sec across the JHK bands. This will be exploited by a pair of multi-object near-IR spectrographs, LUCIFER1 and LUCIFER2, with 4 arc minute field already operating on the telescope. In future, ARGOS will also feed two interferometric imaging instruments, the LBT Interferometer operating in the thermal infrared, and LINC-NIRVANA, operating at visible and near infrared wavelengths. Together, these instruments will offer very broad spectral coverage at the diffraction limit of the LBT's combined aperture, 23 m in size.

The commercial application of membranes in dialysis treatment has started already 40 years ago. Today, dialysis is the application in medicine using the largest number of membrane surface area per year. Integration of the membrane production process into dialyzer manufacturing was the key element in the successful transition from small scale production to large scale dialyzer manufacturing. Automatization techniques are heavily integrated into this process to fulfill the high quality and safety demands in medical technology. This paper gives an overview on the different membrane applications in medical industry. The material selection for manufacturing dialysis membranes and the different membrane morphologies are discussed. In the second part the different manufacturing steps in dialyzer production are presented.

The recent transition frommeshing the whole model to the independent meshing of the assembly parts introduced new challenges in the task of visualizing and pre-processing the finite-element meshes. One part of our work is the visualization and removal of mesh penetrations and perforations, a frequently encountered problem when assembly parts are meshed independently. Furthermore, we focus on the visualization and the interactive definition of mesh-independent connections between car components represented by finite-element meshes. We present methods to automatize the flange recognition, as connections are usually placed along flanges. There are basically three types of connections to visualize and edit: point links, line links and surface links.

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Summary: In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160–1850 g, and mean gestational age of 31 weeks, range: 30–32 weeks, were selected for the study.Due to the increased urinary Na loss, negative Na balance developed in the first 2 weeks followed by positive balance thereafter. PRA, PA, and UAE increased tremendously from the initially high values of 18.2 ± 4.1 ng/ml/hr, 1.7 ± 0.5 ng/ml, and 2.6 ± 0.4 µg/day, mean and SEM, to their maximum of 78.6 ± 18.1 ng/ml/hr, P < 0.01,6.8 ± 3.7 ng/ml, P < 0.05, and 26.4 ± 2.9 µg/day, P < 0.01, in the 3rd week, respectively. Later on, gradual declines occurred, however, PRA, PA, and UAE remained highly elevated even at the 6th week with values of 45.5 ± 15 ng/ml/hr, 1.6 ± 0.5 ng/ml, and 14.5 ± 1.4 µg/day, respectively.It is suggested that late hyponatremia of premature infants is due to tubular unresponsiveness to aldosterone and not to inadequate response of RAAS to stimulation.Speculation: The initially high urinary sodium excretion in premature infants is coupled with low urinary potassium excretion indicating limited renal sodium reabsorption in exchange for potassium. Later on, progressive increase in renal sodium-potassium exchange occurs and the plasma sodium and potassium concentrations gradually approach the normal values.On the basis of these observations, one can assume the physiologic role of both the increasing activity of RAAS and also the increase in renal tubular responsiveness to aldosterone with advancing postnatal age.

Summary: To assess the responsiveness of the renin-angiotensin-aldoste-rone system of the neonate to acute furosemide stimulation and the role of renal prostagladias in mediating the response of the renin-angiotensin-aldosterone system, this study was carried out to determine simultaneously plasma renin activity, plasma aldosterone concentration, urinary abosteroae. prostaglandin E, and prostaglandin F2aexcretion along with determination of plasma electrolyte concentration and urinary electrolyte excretion.Measurements were made on 19 newborn infants with mean birth weight and gestational age of 3009 g (range, 2700 to 4150 g) and 38.7 wk (range, 36 to 41 wk) at the age of 4 to 7 days before and after IM administration of furosemide in a dose of 1 mg/kg.It was demonstrated that in response to furosemide, urine volume (P < 0.001). urinary sodium (P < 0.001). potassium (P < OM), and chloride (P < 0.001) excretion increased significantly.Furosemide administration also resulted in a significant increase from 4.41 f 2.00 to 9.70 f 2.32 ng/ml/hr (P < 0.02) in plasma renin activity, from 1.17 f 0.22 to 1.68 2 0.36 ng/ml (P < 0.025) in plasma aldosterone, from 0.93 f 0.16 to 1.53 f 0.35 pg/12 hr (P < 0.025) in urinary aldosterone, from 17.53 f 3.37 to 23.73 f 3.16 4 1 2 hr (P < 0.025) in prostaglandin E, and from 16.48 2 4.12 to 26.27 2 4.12 ng/l2 hr (P < 0.05) in prostaglandin Fz,.It is concluded that the renin-angiotensin-aldosterone system of the neonate responds to acute furosemide challenge in spite of its high baseline activity, and its response may be mediated by increased renal prostaglandin production.Speculation: The demonstration of high basal activity of the renin-angiotensin-aldosterone system in "nonstimulated" healthy newborn infants prompted us to study whether this high baseline activity is or is not a rate-limiting determinant of the responsiveness of the renin-angiotensin-aldosterone system to furosemide stimulation. It is also to be clarified whether the increase in the activity of the renin-angiotensin-aldosterone system, if any, in response to furosemide administration could be ascribed to its direct effect on renal sodium transport and renal hemodynamics or whether it might be mediated by the furosemide-induced alterations in renal prostaglandin production.

The present study has been carried out to define whether endogenous dopamine contributes to the regulation of renal sodium handling and the function of the renin-angiotensin-aldosterone system in low birth weight premature infants. Twelve premature infants with mean birth weight of 1420 g and mean gestational age of 29.2 wk were given metoclopramide (MTC) in a dose of 0.1 mg kgday to treat delayed gastric emptying, regurgitation, and abdominal distension at the age of 17-23 days. Infants were kept on either a low (2-3 mEqkgday) or high (4-7 mEqkgday) sodium diet to modulate activity of RAAS. Prior to and after a 3-day period of MTC administration, blood samples were taken, and in six male infants 24-h urine collections were made to determine plasma and urine electrolytes, plasma renin activity, plasma aldosterone concentration, and urinary aldosterone excretion. We demonstrated that plasma sodium and potassium concentrations and plasma renin activity were not altered by MTC. On the other hand, in response to MTC, there was a significant increase in urinary sodium excretion (1.8 ±0.3 versus 2.3 ±0.3 mEqkgday) and a decrease in potassium excretion (1.2 ±0.2 versus0.8 ±0.1 mEqkgday); plasma aldosterone concentration and urinary aldosterone excretion decreased significantly from initial values of 2101 ±274 pgml and 2.91 ±0.52 µgday to 1500 ±207 pgml (p< 0.01) and 2.21 ±0.43 µgday (p< 0.01), respectively, after MTC. These alterations were independent of the pretreatment hormone levels. We conclude that in low birth weight premature infants endogenous dopamine has no influence on plasma renin activity and enhances rather than inhibits aldosterone production and renal tubular sodium reabsorption.

Physics-based animation can be generated by performing a complete dynamical simulation of multibody systems. This leads to the solving of a complex system of differential equations in which biomechanical results for the physics of impacts are incorporated. Motion control is achieved by interactively modifying the internal torques. Realtime response requires the distribution of the workload of the computation between a high-speed compute server and the graphics workstation by means of a remote-procedure call mechanism.

Zusammenfassung: VECTA ist eine neue Methode zur Darstellung intrakranieller Gefäße. Mit einer Volume-Rendering-Technik, basierend auf speziellen Hardware-Eigenschaften moderner High-End-Graphik-Workstations, werden aus Spiral-CT-Datensätzen transparente Bilder mit dreidimensionalem Eindruck berechnet. Dadurch können die Gefäße interaktiv überlagerungsfrei aus beliebigen Richtungen visualisiert werden. Zusätzlich besteht die Möglichkeit zu virtuellen endoskopischen Darstellungen, wobei alle dargestellten Strukturen exakt vermessen werden können. VECTA ermöglicht somit die exakte Darstellung des Aneurysmahalses und der Beziehung eines Aneurysmas zu den umgebenden Gefäßen. VECTA wird in Zukunft eine wichtige Rolle bei der Therapieplanung von intrakraniellen Aneurysmen spielen.

To assess the adrenocortical response of premature infants to alterations in sodium balance, the postnatal course of plasma progesterone, 11-deoxycorticosterone, corticosternoe, aldosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol and cortisone was compared in healthy premature infants kept on low (1–2 mEq/kg per day) or high (3–5 mEq/kg per day) sodium diet. The mean birthweight (1470 g, range: 1210–1670 g vs 1410 g, range: 1130–1750 g) and mean gestational age (30.5 weeks, range: 29–32 weeks vs 30.2 weeks, range: 28–32 weeks) in the low and high sodium groups, respectively, were similar. Simultaneous steroid hormone measurements were made weekly up to the 5th week of life using mechanized Sephadex LH-20 multicolumn chromatogaphy and standardized radioimmunoassays. It was demonstrated that in response to renal salt wasting and negative sodium balance there was a significant rise in plasma aldosterone concentration. The plasma levels of other individual corticosteroids generally declined with advancing age, the initial fall, however, was followed by a transient and insignificant but simultaneous increase in 11-deoxycortisol, cortisol, cortisone and corticosterone in prematures on low a sodium diet. This effect could be prevented by giving NaCl supplement. The NaCl-suppressible increase in adrenocortical activity may be the result of the combined effect of stress or angiotensin 11-induced adrenocorticotropic hormone (ACTH) release and/or prolactin-mediated enhanced adrenal response to ACTH.

The study was carried out to assess the possible involvement of excess AVP and free water retention in the development of late hyponatremia by comparing the postnatal course of plasma AVP and urinary excretion of AVP and sodium as well as creatinine, osmolar and free water clearances in premature infants with (group S) and without (group NS) NaCl supplementation. Plasma total protein and albumin concentrations were also determined. Group NS consisted of 8 infants with a birth weight of 1,150–1,730 g (mean: 1,440 g) and gestational age of 28–32 weeks (mean: 30.4 weeks). Group S included 8 infants with a mean birth weight of 1,390 g (range: 980–1,700 g) and a mean gestational age of 30.1 weeks (range: 27–32 weeks). Measurements were made on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 and 1.5–2.5 mmol/kg/day for 8–21 and 22–35 days, respectively. Infants receiving sodium supplements had significantly greater urinary sodium excretion (p < 0.01), retained more sodium (p < 0.01), maintained plasma sodium at normal levels and gained weight at slightly higher rates when compared with those on low sodium. Plasma AVP tended to be higher in group S but did not differ significantly from that in NS group. Urinary AVP excretion, however, either expressed in ng/day or ng/l00 ml GFR, was significantly higher in group S, although the age-related increase could not be seen when correction was made for GFR. The respective values of AVP excretion in weeks 1,2-3 and 4-5 were 1.02 ± 0.17,3.19 ± 0.47 and 2.44 ± 0.22 ng/day in group S and 0.60 ± 0.12, 0.96 ± 0.12 (p < 0.001) and 1.61 ± 0.26 ng/day (p < 0.01) in group NS. NaCl supplementation and the increased AVP excretion was associated with significant decreases in GFR (p < 0.05), free water excretion (p < 0.01), plasma total protein (p < 0.01) and plasma albumin (p < 0.01) concentrations. These data suggest that NaCl supplementation prevents late hyponatremia at the expense of AVP-mediated water retention and subsequent volume expansion.

The effect of low-dose (2–4 μg/kg/min) and long-term (≥ 46 h) dopamine infusion on serum prolactin and thyrotropin concentrations was investigated in 8 preterm infants with hyaline membrane disease. Dopamine was administered for systemic hypotension and/or for impending renal failure. Serum prolactin decreased from 1,314.5 ± 422.7 μU/ml to 489.9 ± 464.1 μU/ml (p < 0.005), while serum thyrotropin fell from 3.77 ± 2.27 μU/ml to 1.01 ± 0.25 μU/ml (p < 0.025) during dopamine infusion. Our data indicate that exogenous dopamine exerts an inhibitory effect on the secretion of prolactin and thyrotropin even in the sick preterm neonate. The role of prolactin in fetal lung maturation and in regulation of the neonatal tissue water stores is discussed. The results of the present study are also useful in explaining the renal effects of long-term low-dose dopamine infusion in the sick preterm infant.

In an attempt to explore the possible role of prolactin (PRL) in the control of neonatal electrolyte homeostasis, this study has been carried out to compare plasma electrolyte concentrations, urine volume and urinary electrolyte excretion as well as plasma PRL levels in healthy full-term neonates with idiopathic edema prior to and after furosemide treatment. No differences in plasma sodium and potassium were demonstrated, edematous neonates, however, had less urine volume and sodium excretion than neonates without edema. Plasma PRL proved to be significantly higher in the edematous group (11.0 ± 1.9 vs. 4.2 ± 3.1 U/l, p < 0.01) but it remained unaltered by furosemide challenge (8.5 ± 1.5 U/l) in spite of the marked elevation of urine flow and sodium excretion. It is concluded that PRL may be involved in the control of the volume and composition of the body fluids in the neonate but further studies are needed to define the effect of changes in body composition on the neonatal PRL secretion.

Urinary PGE excretion was measured by radioimmunoassay in a group of 11 healthy premature infants with a mean birth weight of 1,502 g (range 1,050–1,950 g) and a mean gestational age of 31.6 weeks (range 29–33 weeks), respectively. Measurements were made on the 7th day of life and at weekly intervals thereafter until the 5th week of life. It was demonstrated that urinary PGE excretion significantly increased from the very low level of 6.23 ± 0.70 ng/24 h (mean ± SE) on the 7th day to a value of 17.99 ± 3.53 ng/24 h by the end of the 3rd week (p < 0.005). Later on it remained practically unchanged. It is suggested that its rapid increase during the first 3 weeks of life may be the result of the highly elevated activity of the renin-angiotensin-aldosterone system and it may play a role in controlling renal blood flow.

The role of prolactin in the adaptation of premature infants to the alterations of sodium balance was investigated by measuring plasma prolactin levels serially in 7 low birth weight, premature infants with (group I) and without (group II) NaCl supplementation. The study was performed on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 mEq/kg/day and 1.5–2.5 mEq/kg/day for 8–21 days and 22–35 days, respectively. It was demonstrated that before NaCl supplementation plasma prolactin concentration was similarly elevated in the two groups (6,490 ± 1,291 mU/l in group I versus 7,661 ± 1,094 mU/l in group II), and without supplementation it remained at about the same level throughout the study. When supplemental sodium was given, the plasma prolactin level declined with age at a steady rate to the mean value of 3,516 ± 502 mU/l by the end of 5th week. In the 3rd-5th weeks it proved to be significantly higher in group II than in group I. It is concluded that physiological sodium depletion may account for the prolonged hyperprolactinemia and prolactin might have some importance in the control of sodium homeostasis in low birth weight, premature infants.

To assess the responsiveness of the renin-angiotensin-aldoste-rone system of the neonate to acute furosemide stimulation and the role of renal prostagladias in mediating the response of the renin-angiotensin-aldosterone system, this study was carried out to determine simultaneously plasma renin activity, plasma aldosterone concentration, urinary abosteroae. prostaglandin E, and prostaglandin F2αexcretion along with determination of plasma electrolyte concentration and urinary electrolyte excretion.

In an attempt to provide information about the role of RAAS in development of late hyponatremia in low-birthweight neonates, simultaneous measurement of plasma renin activity, (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UAE) was made using RIA methods along with determination of Na and K balance weekly up to the 6th week of life. Seven healthy male infants with mean birthweight of 1580 g, range: 1160–1850 g, and mean gestational age of 31 weeks, range: 30–32 weeks, were selected for the study.

JAR choriocarcinoma cells have retained several characteristics of normal trophoblasts and have been used as an in vitro trophoblast model. The superfusion system is suitable for the study of hormone synthesis and/or secretion. JAR cells were cultured and transferred to the superfusion system in order to evaluate the spontaneous hCG secretion and the effect of GnRH. The spontaneous hCG release showed a periodic pattern with a 48 min phase interval. In our system single cells and cell-clusters were superfused and there is a possibility that cell to cell connections might have an influence on the regulation of hormone synthesis and/or secretion. GnRH in 4×10−7M and 4×10−6M concentrations or 100 mM KCl caused an immediate hCG release from the JAR cells Repeated administration of GnRH resulted in a delayed hCG release which is probably related to the relatively small amount of hCG available from the storage granules or to the phase of spontaneous secretion.

Background: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established — predominantly in animal studies — in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. Aim: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. Materials and methods: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. Results: In the 2ndand 3rdtrimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. Conclusions: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.

Nine premature infants with birth weight of 1150 to 2500 g and gestational age of 28 to 35 weeks were given dopamine in a dose of 2–4 µg/kg/min to treat cardiopulmonary distress.

Cardiac atrial muscle cells produce a polypeptide hormone that plays a role in the control of water and electrolyte balance and blood pressure. The circulating form of this hormone is the atrial natriuretic peptide (ANP), which contains 28 amino acids. Various immunohistochemical studies have shown that ANP is present in many areas of the central nervous system, including the median eminence. In our studies, we investigated the effect of ANP in a superfused rat pituitary cell system. When ANP was administered at increasing concentrations (0.01 microM to 1 microM), it caused a significant dose-related stimulation of the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The lowest effective dose of ANP in our system was 0.03 microM. When ANP and LH-releasing hormone were administered together, the response was prolonged and had the characteristics of ANP-stimulated LH and FSH release. In contrast with some previous reports, ANP in high concentration (1 microM) consistently induced a small but significant stimulation of the release of corticotropin. ANP did not influence the basal release of prolactin, growth hormone, and thyrotropin.

Modern direct gas injectors for natural-gas-powered internal combustion engines operate at ever-increasing pressures to maximize efficiency. At the operating point of current devices, real gas effects already become relevant, for example in the determination of mass flow rates. These effects have to be considered in the design process of such components. Motivated by this fact, we investigate the real gas effects of high-pressure supersonic methane jets. A discontinuous Galerkin spectral element method for computational fluid dynamics is used in combination with a tabulated equation of state for methane. We first evaluate self-similar profiles for subsonic jets to validate our simulation approach. Then we discuss our simulations of a supersonic jet, where we observe well-resolved shocks and transient structures. Additionally, real and ideal gas modeling are compared and we discuss the significant differences in general flow structure as well as density, pressure and mass flow that occur and make an ideal-gas description inappropriate for our simulation. The influence of pressure level and temperature on the behavior of the jet is discussed. We analyze the influence of the thermodynamic and viscous properties of the gas for the shock location and mass flow. The use of a tabulated equation of state makes jet simulations with occurring phase changes possible. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (ANP) is the most potent endogenous natriuretic/diuretic substance described to date. Recent iinmunohistochemical studies and tests based on radioimmunoassays indicate that AHP is present in the central nervous system. In our studies, we investigated the effect of ANP in a superfused rat pituitary cell system. When ANP was administered at increasing concentrations (10−8M to 10−6M), it caused a significant, dose related stimulation of the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). The lowest effective dose of ANP in our system was 3×108M. When ANP and luteinizing hormone-releasing hormone (LH-RH) were administered together, the response was prolonged and had the characteristics of ANP stimulated LH and FSH release. In contrast with some previous reports, ANP in high concentration (10−6M) consistently induced a small but significant stimulation of the release of corticotropin. ANP did not influence the basal release of prolactin, growth hormone and thyrotropin.