bluuebunny/crossref_metadata_2025 huggingface dataset:
VLSI ARCHITECTURES OF DAUBECHIES WAVELET TRANSFORMS USING ALGEBRAIC INTEGERS
Authors: WAHID KHAN , DIMITROV VASSIL , JULLIEN GRAHAM
Published: May 2005

Two-Dimensional Wavelet Transforms have proven to be highly effective tools for image analysis. In this paper, we present a VLSI implementation of four- and six-coefficient Daubechies Wavelet Transforms using an algebraic integer encoding representation for the coefficients. The Daubechies filters (DAUB4 and DAUB6) provide excellent spatial and spectral locality, properties which make it useful in image compression. In our algorithm, the algebraic integer representation of the wavelet coefficients provides error-free calculations until the final reconstruction step. This also makes the VLSI architecture simple, multiplication-free and inherently parallel. Compared to other DWT algorithms found in the literature, such as embedded zero-tree, recursive or semi-recursive, linear systolic arrays and conventional fixed-point binary architectures, it has reduced hardware cost, lower power dissipation and optimized data-bus utilization. The architecture is also cascadable for computation of one- or multi-dimensional Daubechies Discrete Wavelet Transforms.
AN EVALUATION OF A CONFIGURABLE VLIW MICROARCHITECTURE FOR EMBEDDED DSP APPLICATIONS
Authors: LIU WANLI , ALBONESI DAVID H. , GOSTOMSKI JOHN , PALUM LLOYD , HINTERBERGER DAVE , WANZENRIED RICK , INDOVINA MARK
Published: May 2005

The last decade has witnessed a significant increase in processor offerings geared towards embedded DSP applications. Such processors are commonly VLIW architectures with special ISA and/or microarchitecture features for speeding up signal processing functions and customization options to improve cost/performance. The Jazz Programmable System Architecture from Improv Systems is one such processor offering. Jazz employs a VLIW architecture which is well-suited to the characteristics of embedded DSP applications such as voice over packet, media processing, and home connectivity. The microarchitecture incorporates overlaid datapaths, distributed register file and memory systems, code compression, and parallel computation and memory access. Jazz permits design-time configuration in an attempt to bridge the gap between the flexibility of a programmable processor and the cost-benefit of full customization.

In this paper, we explore the cost/performance tradeoffs of the Jazz microarchitecture on various embedded multimedia applications using a detailed cycle-level simulator as well as area and power models. Through a comparison of the performance, power, and area of different hardware configurations running these applications, we demonstrate how the configurability of the architecture affords a cost-performance benefit over a fixed microarchitecture. Key features of the microarchitecture are quantitatively evaluated in terms of their influence on performance. The relationship between compiler optimizations and processor performance is also explored.
A DISCRETE WAVELET TRANSFORM CODEC DESIGN
Authors: HU YI-QIANG , WU BING-FEI , SU CHORNG-YANN
Published: May 2005

This manuscript presents a VLSI architecture and its design rule, called embedded instruction code (EIC), to realize discrete wavelet transform (DWT) codec in a single chip. Since the essential computation of DWT is convolution, we build a set of multiplication instruction, MUL, and the addition instruction, ADD, to complete the work. We segment the computation paths of DWT according to the multiplication and addition, and apply the instruction codes to execute the operators. Besides, we offer a parallel arithmetic logic unit (PALU) organization that is composed of two multipliers and four adders (2M4A) in our design. Thus, the instruction codes programmed by EIC control the PALU to compute efficiently. Additionally, we establish a few necessary registers in PALU, and the number of registers depends on the wavelet filters' length and the decomposition level. Yet, the numbers of multipliers and adders do not increase as we execute the DWT or the inverse DWT (IDWT) in multilevel decomposition. Furthermore, we deduce the similarity between DWT and IDWT, so the functions can be integrated in the same architecture. Besides, we schedule the instructions; thus, the execution of the multilevel processes can be achieved without superfluous PALU in a single chip. Moreover, we solve the boundary problem of DWT by using the symmetric extension. Therefore, the perfect reconstruction (PR) condition for DWT requirement can be accomplished. Through EIC, we can systematically generate a flexible instruction codes while we adopt different filters. Our chip supports up to six levels of decomposition, and versatile image specifications, e.g., VGA, MPEG-1, MPEG-2, and 1024×1024 image sizes. The processing speed is 7.78 Mpixel/s when the operation frequency, for normal case, is 100 MHz.
MODELLING AND ANALYSIS OF THE SPREAD OF MALARIA: ENVIRONMENTAL AND ECOLOGICAL EFFECTS
Authors: SINGH SHIKHA , SHUKLA J. B. , CHANDRA PEEYUSH
Published: May 2005

In this paper, general SIS and SIRS models with immigration of human population for the spread of malaria are proposed and analyzed. Effects of natural as well as human population density related environmental and ecological factors, which are conductive to the survival and growth of mosquito population, are considered. It is shown in both the cases that as the parameters governing environmental and ecological factors increase, the spread of malaria increases. It is also found that due to immigration, this infectious disease becomes more endemic.
REALISTIC PATTERNS OF INHERITANCE OF SICKLE-CELL ANEMIA GENE: A THEORETICAL APPROACH
Authors: TCHUENCHE JEAN M.
Published: May 2005

We derive equations which describe the reproductive interactions of human individuals in a population governed by their genotype structure. The model assumes reproduction within a specified age interval and the approach is basically theoretical. Some fundamental properties of the renewal equations as well as the interaction function are listed. It is significant that genetic screening prior to marriage still remains the principal preventive measure in order to avoid an increase in the population of those suffering from genetic defects.
A NEW APPROACH TO PEST MANAGEMENT PROBLEM
Authors: BHATTACHARYYA S. , BHATTACHARYA D. K.
Published: May 2005

The paper deals with the effect of pesticide on the pest affecting a paddy field and also on the fishes living in the soil water. An objective function is formed in terms of projected loss of individual fish, the projected profit of killing a pest and the cost of spraying insecticide for a finite time period. Next the corresponding pest management model is formed by considering the growth equations of paddy, pest, and fish of the soil water. The model is analyzed by control theoretic means to determine the threshold limits of pesticide to be used. Lastly, the optimal value of pesticide is obtained. It is shown that the optimal value lies within the threshold limits. Finally corresponding to this optimal threshold value of pesticide, the optimal values of the biomass of paddy and that of the fish of the soil water are also obtained. The results are finally verified numerically by special choice of parameters compatible with the model.
POWER-LAWS IN THE COMPLETE SEQUENCES OF HUMAN GENOME
Authors: CHEN YAW-HWANG , NYEO SU-LONG , YU JUI-PING
Published: May 2005

The distance distributions of the four types of bases A, C, G and T in the complete sequences of human genome are shown to have long-tail power-law but short-distance exponential behaviors. However, the random sequences with identical numbers of bases show only short-distance exponential behaviors. The DNA sequence of E. coli, which is much shorter than human's, is shown to exhibit essentially exponential behavior as its corresponding random sequence. Also, DNA sequence of human's with smaller C + G content is seen to enjoy longer power-law tail in its distributions of C and G. The coefficient in the exponential decaying function shows a linear dependent with the C + G content but the decay exponent in the power-law shows no such dependence.
INFORMATION GEOMETRY AND ENCODING THE BIOSYSTEMS ORGANIZATION
Authors: LERNER VLADIMIR S.
Published: May 2005

The paper analyzes Information Geometry (IG) generated by the evolutionary Information Macrodynamics (IMD) which are memorized by IG renovated geometrical structures. The IG encloses a cellular structure which carries a genetic code for the IMD restoration. The paper focuses on the natural enfolding of the universal optimal genetic code into the IG, obtained from the preceding dynamics, with a forthcoming creation of initial genetic information by the IG cells. The field of information geometry consists of the cell's sets that enable the discrete production of a quantum of information at the cells' boundaries. A particular spatial–time dynamic trajectory, located on a curved information space, enfolds and encodes a specific triplet's code, accumulated by the IG cellular information structure. The paper explores a potential conversion of imaginary into real information, associated with the transformation of mind into matter, and evaluates the dissimilar directional "difficulty" of crossing the boundary between imaginary, virtual and physical real information. The attractive information forces, as attributes of the curved IG, assemble the elementary quantums of time-space virtual dynamics into the cooperative macrostructures and information networks. The results analytically prove for the first time that a macrostructure's genetic information is enfolded into the IG geometrical structures. This means that the morphology of any biological macrostructure, as well as its external surface and inner structures, encloses the code of the macrostructure's genetic information. The complexity of encoded macrostructure depends not just on the total number of its corresponding code's symbols, but essentially on the complexity of the coding structure presented by a hierarchy of the code's symbols. This information systemic property, applied to the encoding of biogenetic information, demonstrates that the same gene's number (for different bio-species) can encode proteins with a variety of distinctive complexities, characterizing the huge diversity of biosystems from plants to humans.
DIAMETER FORMULAS FOR A CLASS OF UNDIRECTED DOUBLE-LOOP NETWORKS
Authors: CHEN BAOXING , XIAO WENJUN , PARHAMI BEHROOZ
Published: May 2005

An n-node network, with nodes numbered 0 to n-1, is an undirected double-loop network with chord lengths 1 and s(2≤s<n/2) when each node i(0≤i<n) is connected to each of the four nodes i±1 and i±s via an undirected link; all node-index expressions are evaluated modulo n. Let n=qs+r, where r(0≤r<s) is the remainder of dividing n by s. Furthermore, let s=ar+b, where b(0≤br and for a subcase of the case q≤r when b≤aq+1. In the complementary subcase of q≤r, when b>aq+1, network diameter can be derived by applying the O(log n)-time algorithm of Zerovnik and Pisanski (J. Algorithms, Vol. 14, pp. 226-243, 1993). Obtaining a closed-form formula for diameter of the double-loop network in the latter subcase remains an open problem.
LOAD SHARING VERSUS SERVICE BALANCING IN INTEGRATED NETWORKS
Authors: LINCKE SUSAN J. , HOOD CYNTHIA S.
Published: May 2005

As third and fourth generation cellular/wireless networks evolve, operators must learn to efficiently manage diverse services, and multiple networks consisting of varying technologies, cell sizes, and frequency bands. Architectural studies on integrated heterogeneous networks suggest that vertical handovers can be used to increase network efficiency. We propose that carefully-controlled load distribution can also promote Quality of Service (QoS) goals for the diverse services. This study compares session overflow and session placement algorithms in order to determine their effects on efficiency and QoS.
TOWARDS COMPUTING BRAIN DEFORMATIONS FOR DIAGNOSIS, PROGNOSIS AND NEUROSURGICAL SIMULATION
Authors: MILLER KAROL , TAYLOR ZEIKE , NOWINSKI WIESLAW L.
Published: May 2005

The objective of our research is to create a system computing brain deformations. We have in view both clinical and training applications, such as "brain shift" calculation, prognosis and diagnosis of development of brain diseases as well as surgical simulators for planning and education. In this paper, we specifically address issues related to creating geometrically and mechanically precise representations of the brain. The method comprises of the following steps: (1) development of a 3D anatomical brain atlas, (2) construction of a finite element mesh of the atlas, (3) creation of a mathematical model, and (4) development of an efficient computational model. We discuss two types of approaches to model deformation behavior of the brain: single-phase brain tissue model, suitable for analysis of relatively short events such as surgical actions; and bi-phasic brain tissue model, well suited for calculations leading to prognosis of the development of diseases. As an illustration of the presented concepts we provide examples of 3D meshing, calculation of reaction force acting on a surgical tool using a single-phase mathematical model, and calculations of the development of hydrocephalus and the effects of tumor growth using the bi-phasic modeling approach.
ANALYSIS OF THE BENDING BEHAVIOR OF THE LUMBAR SPINE DURING POSTEROANTERIOR MOBILIZATION
Authors: LEE RAYMOND Y. W. , TSUNG BONNIE Y. S. , EVANS JOHN , TONG PIN
Published: May 2005

This research study aimed to measure the bending stiffness of the lumbar spine when subjected to posteroanterior mobilization. The lumbar spine was modeled as an initially curved beam column supported over the rib cage and the pelvis. Together with the posteroanterior mobilization force acted on the spine formed the three-point bending of the beam. The bending stiffness of the spine was derived from the mobilization force and the change in curvature of the spine. The mobilization force was measured by mounting a force plate onto the mobilization couch, and electromagnetic sensors were used to measure the change in spinal curvature. The mean bending stiffness of the spine was found to be 38.5 Nm2. The theoretical modelling suggested that the pelvic rotation produced by mobilization may be employed to provide an indicator of the magnitude of the mobilization force.
NUMERICAL APPROACH TO FLUID-STRUCTURE ANALYSIS OF SOFT BIOLOGICAL TISSUE
Authors: NG E. Y. K. , GHISTA DHANJOO N. , JEGATHESE R. C.
Published: May 2005

Elasticity problems can be formulated into partial differential equations while analyzing the behavior of fluid-structure coupled problems. The current focus is to study the perfusion and instantaneous material property change in the soft tissues such as myocardium, which is analyzed due to the varying stiffness conditions. The analysis performed has considered physiological range loading conditions.
PHYSIOMIC APPROACH TO BIOMECHANICS OF CORONARY MICROCIRCULATION
Authors: KAJIYA MASAHITO , HIRAMATSU OSAMU , YADA TOYOTAKA , TOYOTA EIJI , KIYOOKA TAKAHIKO , MOHRI SATOSHI , SHIMIZU JUICHIRO , OGASAWARA YASUO , KAJIAYA FUMIHIKO
Published: May 2005

The recently proposed Physiome is considered as a powerful successor to the Genome. The definition of Physiome is the quantitative description of the physiological dynamics or functions of the intact organism. The physiome includes integration of knowledge through functional modules of hierarchical system elements of biological systems, and modeling. Biomechanics will offer potent tools to promote the Physiome. By using modern microvisualization technology with physiomic model, this manuscript introduces our physiomic approach to coronary microcirculation which supplies oxygen and nutrients to heart muscles;

1. Mechanical interaction between coronary blood flow and cardiac contraction, and

2. Capillary network and its function.
NUMERICAL AND EXPERIMENTAL STUDY ON THE RELATIONSHIP BETWEEN BLOOD CIRCULATION AND PERIPHERAL TEMPERATURE
Authors: HE YING , LIU HAO , HIMENO RYUTARO , SHIRAZAKI MINORU
Published: May 2005

Computational simulation of the thermal transport phenomena in the human body has recently aroused a great deal of interest among researchers, because it can be applied in different areas such as medicine, rehabilitation, space suits, and others. In this study, we developed a coupling model to analyze the temperature distribution of the human middle finger. Firstly, a one-dimensional thermo-fluid model of blood circulation in the human upper limb is constructed. Secondly, a two-dimensional thermal model of the human finger, which consists of skin, tendon, bone, main arteries, and veins is developed. The two models are further coupled weakly through data transfer. The blood pressure, blood flow rate, and blood temperature at different vessel sites and the tissue temperature are thus obtained. The effect of viscosity on the finger skin temperature was also investigated. Simultaneously, the thermograms of the human hand were also obtained using thermograpy under the resting condition and after jogging, to observe the variation in the blood circulation. The temperature at different points was extracted from the thermograms. It is observed that there is a periodic variation in skin temperature near the blood vessels after jogging. It is expected that this coupling model will be applicable to hyperthermia, drug delivery, and sports training.
EFFECT OF THE MYOCARDIUM NON-UNIFORMITY ON THE HEART FUNCTIONAL RESERVE
Authors: BLYAKHMAN FELIX A. , MARCHENKO ELENA V. , KOLCHANOVA SVETLANA G. , ZINOVEVA JULIA A. , MIRONKOV BORIS L. , NAIDICH ANNA M. , CHESTUKHIN VASILY V. , SHUMAKOV VALERY I.
Published: May 2005

The goal of this study is to understand the role of structural-and-functional inhomogeneity (SFI) in the left ventricular (LV) wall. According to the peculiarities of heart diseases development, we supposed the existence of causal relationship between SFI and the heart functional reserve, i.e. an ability to maintain pump function in case of additional load. Here, we looked into the functional aspect of SFI phenomenon. Sixteen IHD patients with a different extent of coronary artery stenotic lesion were chosen for this investigation. The patients were underwent the transesophageal ultrasound examinations, and LV 3D reconstruction was performed. To estimate the extent of the functional non-uniformity, the myocardium elastic properties in LV wall regions and LV regional motion were defined. We found out a strong inverse correlation between the extent of LV functional non-uniformity and the heart functional reserve, estimated as a patients' tolerance to physical load. We concluded that the transition of functional myocardium non-uniformity due to IHD development reflects the exhaust of heart functional reserve.
CLASSIFICATION OF HUMAN FACIAL AND AURAL TEMPERATURE USING NEURAL NETWORKS AND IR FEVER SCANNER: A RESPONSIBLE SECOND LOOK
Authors: NG E. Y. K. , CHONG COLIN , KAW G. J. L.
Published: May 2005

Severe Acute Respiratory Syndrome (SARS) is a highly infectious disease caused by a coronavirus. Screening to detect potential SARS infected subject with elevated body temperature plays an important role in preventing the spread of SARS. The use of infrared (IR) thermal imaging cameras has thus been proposed as a non-invasive, speedy, cost-effective and fairly accurate means for mass blind screening of potential SARS infected persons. Infrared thermography provides a digital image showing temperature patterns. This has been previously utilized in the detection of inflammation and nerve dysfunctions. It is believed that IR cameras may potentially be used to detect subjects with fever, the cardinal symptom of SARS and avian influenza. The accuracy of the infrared system can, however, be affected by human, environmental, and equipment variables. It is also limited by the fact that the thermal imager measures the skin temperature and not the body core temperature. Thus, the use of IR thermal systems at various checkpoints for mass screening of febrile persons is scientifically unjustified such as what is the false negative rate and most importantly not to create false sense of security.

This paper aims to study the effectiveness of infrared systems for its application in mass blind screening to detect subjects with elevated body temperature. For this application, it is critical for thermal imagers to be able to identify febrile from normal subjects accurately. Minimizing the number of false positive and false negative cases improves the efficiency of the screening stations. False negative results should be avoided at all costs, as letting a SARS infected person through the screening process may result in potentially catastrophic results. Hitherto, there is lack of empirical data in correlating facial skin with body temperature. The current work evaluates the correlations (and classification) between the facial skin temperatures to the aural temperature using the artificial neural network approach to confirm the suitability of the thermal imagers for human temperature screening. We show that the Train Back Propagation and Kohonen self-organizing map (SOM) can form an opinion about the type of network that is better to complement thermogram technology in fever diagnosis to drive a better parameters for reducing the size of the neural network classifier while maintaining good classification accuracy.
MINIATURIZED PCR-CHIP FOR DNA AMPLIFICATION WITH AN EXTERNAL PERISTALTIC PUMP
Authors: YU HUI-MIN , CHIEN CHAO-HENG
Published: May 2005

Since 1985, the polymerse chain reaction (PCR) became very popular among the field of molecular biology. It is very powerful for amplification DNA segment and it had a variety of applications in medicinal, virus, disease, and monitoring. In this study, a simple and miniature PCR chip will be presented with an external peristaltic pump utilized to driving liquid into PCR chip.1 The PCR chip was made of PMMA (Polymethylmethacrylate) and glass. The hot embossing technique was used to fabricate the micro channel on the PMMA. The copper was sputtered on the glass as the heater. The glass and PMMA were bonded by PDMS. In typically, heater temperature was 94°C for denature, 55°C for annealing, 72°C for extension. Therefore, the heaters formed three different zones of temperature along the channel that the length ration on each temperature zone was 1:1:2 for denature, annealing and extension, respectively.2,3 For temperature control, the PID control mode was used to regulate the temperature on reaction and the DC power was as the power supplier. The thermal sensors were adhered on the heater beside the channel.
Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes
Authors: Kralisch Susan , Klein Johannes , Lossner Ulrike , Bluher Matthias , Paschke Ralf , Stumvoll Michael , Fasshauer Mathias
Published: May 2005

Visfatin is a novel adipocytokine exerting insulin-mimetic effects in various insulin-sensitive tissues such as liver, muscle, and fat. In contrast, interleukin (IL)-6 is a proinflammatory adipose-secreted factor that induces insulin resistance and plasma concentrations that correlate with the development of type 2 diabetes mellitus. In the present study, the impact of IL-6 on visfatin gene expression in 3T3-L1 adipocytes was determined by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, 30 ng/ml IL-6 time-dependently downregulated visfatin synthesis with a significant 40% suppression seen after 4 h of treatment. Furthermore, the addition of IL-6 for 16 h dose-dependently suppressed visfatin mRNA with significant effects first observed at concentrations as low as 3 ng/ml and a maximal 43% reduction at 30 ng/ml effector. Moreover, inhibitor studies suggested that the negative effect of IL-6 on visfatin expression is, at least in part, mediated by p44/42 mitogen-activated protein kinase. In contrast, troglitazone did not reverse the negative effect of IL-6 on visfatin synthesis under these conditions. Taken together, our study suggests that IL-6 might influence glucose tolerance in part by regulation of the novel insulin-mimetic adipocytokine visfatin.
SMP-534 inhibits TGF-β-induced ECM production in fibroblast cells and reduces mesangial matrix accumulation in experimental glomerulonephritis
Authors: Sugaru Eiji , Sakai Mutsuko , Horigome Kazuhiko , Tokunaga Teruhisa , Kitoh Makoto , Hume W. Ewan , Nagata Ryu , Nakagawa Tsutomu , Taiji Mutsuo
Published: May 2005

Transforming growth factor-β (TGF-β) is a potent fibrotic factor responsible for the synthesis of extracellular matrix (ECM) and is implicated as the major determinant in pathogenesis of chronic fibroses, including kidney. The novel small compound SMP-534 reduced ECM production induced by TGF-β in fibroblast cells. SMP-534 inhibited TGF-β-induced p38 mitogen-activated protein kinase (p38) activation but did not inhibit epidermal growth factor (EGF)-induced extracellular signal-related kinase (ERK) activation. We also found that oral administration of SMP-534 dose dependently lowered hydroxyproline contents in the cortical region of the kidney in rat anti-Thy-1 nephritis models. In periodic acid-Schiff staining of kidney sections, ECM accumulation was reduced by SMP-534 treatment. These data indicate that SMP-534 has potential in therapy for fibrotic diseases, including nephropathy.
Modeling GFR trajectories in diabetic nephropathy
Authors: Lemley Kevin V. , Boothroyd Derek B. , Blouch Kristina L. , Nelson Robert G. , Jones Lois I. , Olshen Richard A. , Myers Bryan D.
Published: May 2005

In an 8-year longitudinal study of Pima Indians with type 2 diabetes and nephropathy, we used statistical techniques that are novel and depend on minimal assumptions to compare longitudinal measurements of glomerular filtration rate (GFR). Individuals enrolled with new-onset microalbuminuria either progressed to macroalbuminuria (progressors, n = 13) or did not progress (nonprogressors, n = 13) during follow-up. Subjects with new-onset macroalbuminuria at screening were also followed ( n = 22). Patients had their GFR determined serially by urinary iothalamate clearances (average 11 clearances; range 6–19). GFR courses of individuals were modeled using an adaptation of smoothing and regression cubic B-splines. Group comparisons were based on five-component vectors of fitted GFR values using a permutation approach to a Hotelling’s T2statistic. GFR profiles of initially microalbuminuric progressors differed significantly from those of nonprogressors ( P = 0.003). There were no significant baseline differences between progressors and nonprogressors with respect to any measured clinical parameters. The course of GFR in the first 4 yr following progression to macroalbuminuria in initially microalbuminuric subjects did not differ from that in newly screened macroalbuinuric subjects ( P = 0.27). Without imposing simplifying models on the data, the statistical techniques used demonstrate that the courses of decline of GFR in definable subgroups of initially microalbuminuric diabetic Pima Indians, although generally progressive, follow distinct trajectories that are related to the extent of glomerular barrier dysfunction, as reflected by the evolution from microalbuminuria to macroalbuminuria.
Activated extracellular signal-regulated kinases are necessary and sufficient to initiate tubulogenesis in renal tubular MDCK strain I cell cysts
Authors: Hellman Nathan E. , Greco Andres J. , Rogers Katherine K. , Kanchagar Chitra , Balkovetz Daniel F. , Lipschutz Joshua H.
Published: May 2005

A classic in vitro model of renal cyst and tubule formation utilizes the Madin-Darby canine kidney (MDCK) cell line, of which two strains exist. Most cyst and tubule formation studies that utilized MDCK cells have been performed with MDCK strain II cells. MDCK strain II cells form hollow cysts in a three-dimensional collagen matrix over 10 days and tubulate in response to hepatocyte growth factor, which increases levels of active (phosphorylated) ERK1/2. In this study, we demonstrate that MDCK strain I cells also form cysts when grown in a collagen matrix; however, MDCK strain I cell cysts spontaneously initiate the primary steps in tubulogenesis. Analysis of time-lapse microscopy of both MDCK strain I and strain II cell cysts during the initial stages of tubulogenesis demonstrates a highly dynamic process with cellular extensions and retractions occurring rapidly and continuously. MDCK strain I cell cysts can spontaneously initiate tubulogenesis mainly because of relatively higher levels of active ERK in MDCK strain I, compared with strain II, cells. The presence of either of two distinct inhibitors of ERK activation (UO126 and PD09059) prevents tubulogenesis from occurring spontaneously in MDCK strain I cell cysts and, in response to hepatocyte growth factor, in strain II cell cysts. The difference between MDCK strain I and strain II cell lines is likely explained by differing embryological origins, with strain I cells being of collecting duct, and hence ureteric bud, origin. Ureteric bud cells also have high levels of active ERK and spontaneously tubulate in our in vitro collagen gel system, with tubulogenesis inhibited by UO126 and PD09059. These results suggest that a seminal event in kidney development may be the activation of ERK in the mesonephric duct/ureteric bud cells destined to form the collecting tubules.
Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter
Authors: Goytain Angela , Quamme Gary A.
Published: May 2005

We have begun to identify and characterize genes that are differentially expressed with low magnesium. One of these sequences conformed to the ancient conserved domain protein, ACDP2. Real-time RT-PCR of mRNA isolated from distal epithelial cells cultured in low-magnesium media relative to normal media and in kidney cortex of mice maintained on low-magnesium diets compared with those animals consuming normal diets confirmed that the ACDP2 transcript is responsive to magnesium. Mouse ACDP2 was cloned from mouse distal convoluted tubule cells, expressed in Xenopus laevis oocytes, and studied with two-electrode voltage-clamp studies. When expressed in oocytes, ACDP2 mediates saturable Mg2+uptake with a Michaelis constant of 0.56 ± 0.05 mM. Transport of Mg2+by ACDP2 is rheogenic, is voltage-dependent, and is not coupled to Na+or Cl−ions. Expressed ACDP2 transports a range of divalent cations: Mg2+, Co2+, Mn2+, Sr2+, Ba2+, Cu2+, and Fe2+; accordingly, it is a divalent cation transporter with wide substrate selectivity. The cations Ca2+, Cd2+, Zn2+, and Ni2+did not induce currents, and only Zn2+effectively inhibited transport. The ACDP2 transcript is abundantly present in kidney, brain, and heart with lower amounts in liver, small intestine, and colon. Moreover, ACDP2 mRNA is upregulated with magnesium deficiency, particularly in the distal convoluted tubule cells, kidney, heart, and brain. These studies suggest that ACDP2 may provide a regulated transporter for Mg2+and other divalent cations in epithelial cells.
Elevation of Serum Albumin Levels in Nagase Analbuminemic Rats by Allogeneic Bone Marrow Cell Transplantation
Authors: Hua L. , Aoki T. , Jin Z. , Nishino N. , Yasuda D. , Izumida Y. , Morohara K. , Koizumi T. , Shimizu Y. , Murai N. , Kusano M.
Published: May 2005

We investigated the feasibility of correcting the congenital absence of albumin in Nagase analbuminemic rats (NARs) by allogeneic bone marrow cell transplantation (BMT). Seven-week-old male NARs were used as recipients, and 6- to 8-week-old male Sprague-Dawley (SD) rats were used as allograft donors. NARs were divided into three groups: a BMT group (n = 10) in which bone marrow cells were infused into the liver; a hepatocyte transplantation (HCT) group (n = 8) in which hepatocytes were transplanted into the liver, and a control group (n = 8) in which PBS was injected into the portal vein. Serum albumin levels were measured as an indicator of the function of the grafted cells, and the phenotypic characteristics of the engrafted cells in the recipient’s liver were assessed with immunohistochemical and immunofluorescence techniques. At 8 weeks after cell transplantation, the serum albumin levels of the BMT group and HCT group were significantly higher than in the control group. The hepatocyte-like cells derived from bone marrow cells expressed albumin in liver of the NARs. According to this result, bone marrow cells can differentiate into hepatocyte-like cells in vivo. The results show that BMT is an effective treatment for congenital analbuminemia in a rat model and suggest that allogeneic BMT can be used as an efficient therapy for hereditary metabolic diseases.
IL-6 and Its Circadian Secretion in Humans
Authors: Vgontzas A.N. , Bixler E.O. , Lin H.-M. , Prolo P. , Trakada G. , Chrousos G.P.
Published: May 2005

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.
Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats
Authors: Cano Pilar , Cardinali Daniel P. , Jimenez Vanessa , Alvarez Maria P. , Cutrera Rodolfo A. , Esquifino Ana I.
Published: May 2005

Objective: Interferon-γ (IFN-γ) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. Methods: Groups of 6–8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-γ (105 IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. Results: A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-γ-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-γ administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. Conclusion: The data point out an effect of IFN-γ on the mechanisms responsible for the circadian organization of pituitary hormone release.
Cerebrospinal Fluid and Neutrophil Respiratory Burst after Subarachnoid Hemorrhage
Authors: Trabold B. , Rothoerl R. , Wittmann S. , Woertgen C. , Fröhlich D.
Published: May 2005

Objectives: To investigate the effect of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on the activation of polymorphonuclear neutrophils (PMN) in response to receptor-dependent stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine and TNFα or non-receptor-dependent stimulation with phorbol 12-myristate 13-acetate. Methods: CSF from 12 patients with SAH due to ruptured cerebral aneurysm was collected. Samples of CSF were drawn at different time points. CSF from 6 healthy subjects receiving spinal anesthesia served as the control group. After stimulation of PMN the generation of reactive oxygen intermediates was analyzed on a flow cytometer. Results: In the presence of CSF, PMN showed a significant suppression of the oxidative burst following stimulation compared to stimulation without CSF. The reduction of the oxidative burst following stimulation was higher in the presence of CSF from patients with SAH. After pretreatment at 56°C, the extent of the suppression observed following receptor-dependent stimulation and CSF from patients with SAH was similar to that seen after stimulation with CSF from healthy individuals. Conclusions: These data show that the presence of CSF resulted in a suppression of neutrophil oxidative function. A more distinct depression was seen in the presence of CSF from patients with SAH. We suggest a complex physiological inhibitory and protective mechanism against unfavorable activation of PMN by CSF.
Human Endometrial Leukemia Inhibitory Factor and Interleukin-6: Control of Secretion by Transforming Growth Factor-β-Related Members
Authors: Perrier d’Hauterive Sophie , Charlet-Renard Chantal , Dubois Michel , Berndt Sarah , Goffin Frederic , Foidart Jean-Michel , Geenen Vincent
Published: May 2005

Objective(s): The implantation process is closely linked to the fundamental question of the tolerance of the maternal immune system. The main objective of this study was to investigate whether different members of the transforming growth factor-β (TGF-β) superfamily could intervene in the first steps of embryo implantation by modulating the secretion of proimplantatory leukemia inhibitory factor (LIF) and in the tolerance of the fetal graft by regulating proinflammatory interleukin (IL)-6 secretion by human endometrial epithelium (EEC) in vitro. Methods: EEC were isolated from biopsies collected from 16 informed and consenting fertile women and were cultured for 72 h. Cytokine measurements (LIF and IL-6) were realized by ELISA. Results: TGF-β1 (from 10–12 to 10–8M), -β2, -β3 and activin A (10–10 and 10–8M) increased LIF secretion by EEC cultures. Inhibin B (10–10 and 10–8M) did not stimulate LIF production by human EEC. Contrastingly, TGF-β1 (from 10–12 to 10–8M), -β2, -β3 and activin A (10–10 and 10–8M) reduced IL-6 release by the same cells. Activin A at 10–8 M also significantly reduced the stimulating effect of IL-1β (10–9M) which is known to stimulate LIF production by EEC. Only the highest concentration of inhibin B (10–8M) reduced IL-6 secretion by EEC, but did not modulate IL-1β-induced stimulation of IL-6 secretion. Conclusion(s): Besides their role in the control of the process of implantation and in the induction of embryonic mesoderm, different members of the TGF-β superfamily may also contribute in the reproductive process by enhancing endometrial proimplantatory LIF secretion and reducing proinflammatory IL-6 release by EEC.
Effects of Space Flight Conditions on the Function of the Immune System and Catecholamine Production Simulated in a Rodent Model of Hindlimb Unloading
Authors: Aviles Hernan , Belay Tesfaye , Vance Monique , Sonnenfeld Gerald
Published: May 2005

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. Objective: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. Methods: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. Results: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. Conclusion: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections.
Lipopolysaccharide-Induced Leptin Synthesis and Release Are Differentially Controlled by Alpha-Melanocyte-Stimulating Hormone
Authors: Mastronardi Claudio A. , Srivastava Vinod , Yu Wen H. , Dees W. Les , McCann S.M.
Published: May 2005

Objective: Since α-melanocyte-stimulating hormone (α-MSH) inhibits the synthesis and release of proinflammatory cytokines and stimulates the synthesis and release of anti-inflammatory cytokines, and leptin is a cytokine that has anti-inflammatory actions in the presence of lipopolysaccharide (LPS), we hypothesized that α-MSH increases leptin synthesis and release. Methods: α-MSH or 0.9% NaCl (saline) were injected intraperitoneally 15 min prior to intravenous injection of 0.5 ml of saline or LPS (0.15 mg/kg). Thereafter, repeated blood samples were withdrawn over a period of 6 h and plasma leptin concentrations determined. The rats were sacrificed at 6 h and leptin mRNA was measured in epididymal fat pads. Results: Plasma leptin concentrations of the saline-injected control group were unaltered during the 6 h, whereas in the LPS group, leptin was unaltered between 0 and 30 min and thereafter progressively increased between 30 and 360 min by 2.5-fold. α-MSH slightly increased plasma leptin concentrations by 15 min and then increased them further by 120 min, after which they declined towards baseline. The pattern of plasma leptin concentrations in the α-MSH + LPS group was similar to that of the LPS group, except that higher concentrations were observed at 120 min in the rats injected with α-MSH + LPS. LPS increased leptin mRNA by 3-fold at 6 h, whereas it was unaffected in the MSH-treated animals. On the contrary, α-MSH completely blocked the LPS-induced leptin mRNA. Conclusions: Our results suggest that α-MSH increased leptin release without altering its synthesis, but when LPS increased release and synthesis of leptin, α-MSH, although further increasing release, blocked the enhanced synthesis of leptin elicited by LPS.
Impaired Washout – Embolism and Ischemic Stroke: Further Examples and Proof of Concept
Authors: Sedlaczek O. , Caplan L. , Hennerici M.
Published: May 2005

We previously posited that impaired washout of emboli was an important mechanism of brain infarction in patients with cerebral hypoperfusion. Hyperviscosity and hypoperfusion enhance thrombus formation promoting embolization of fresh thrombi. Hypoperfusion also reduces dissolution of emboli due to reduced flow velocity leading to classic hemodynamic patterns of stroke. To prove this concept further, we identified patients with severe hemodynamic compromise of either arterial or venous origin, or both, and natural or iatrogenic mechanisms of embolism. Three conditions were investigated in a stroke MRI protocol: 5 patients who had conventional cerebral angiography for the diagnosis of moyamoya disease, 1 patient with atrial fibrillation and thrombosis of the left transverse dural sinus and 1 patient with a patent foramen ovale with atrial septum aneurysm presenting with thrombosis of cortical cerebral veins. In all patients, subcortical arterial embolization within an atypical borderzone of hypoperfusion was observed.
Improvement Pattern in the Clock Drawing Test in Early Alzheimer’s Disease
Authors: Cacho Jesús , García-García Ricardo , Fernández-Calvo Bernardino , Gamazo Silvia , Rodríguez-Pérez Roberto , Almeida Aghostino , Contador Israel
Published: May 2005

Objective: The aim of this paper was to compare the performance of a group of patients with early Alzheimer’s disease (EAD) against a control group of healthy control (HC) subjects in the Clock Drawing Test (CDT), i.e. verbal command versus copying of a clock model presented to the subject. Patients and Methods: The authors have studied 140 subjects; 70 patients with probable EAD, with a mean age of 76.4 ± 7.64 years and a clinical dementia rating stage 1 (mild dementia), and70 HC with a mean age of 75.16 ± 6.34 years. Results: Patients in the EAD group obtained significantly higher scores on the copy command mode than on the verbal command mode (Z = –7.129, p < 0.001) – improvement pattern of the CDT – whereas no statistically significant differences were found in the HC group (Z = –2.001, p < 0.080). Within the group of EAD patients, we have noticed that there is a correlation between the copy command mode and the visual-constructive functions of the Cambridge Cognitive Examination (CAMCOG) (r = 0.607, p < 0.01), while the memory functions of the CAMCOG correlate with the verbal command mode (r = 0.704, p < 0.01). Conclusions: In our study, the EAD patients show an improvement pattern in the execution of the CDT copy command in comparison with the execution of the CDT verbal command, which we did not observe in the HC group. Such results might be associated with a greater deterioration of the memory functions when compared with the visual-constructive ones in the patients with EAD.
Urinary Steroid Excretion Rates in Acromegaly
Authors: Vierhapper H. , Nowotny P. , Waldhäusl W.
Published: May 2005

Using gas chromatography/mass spectrometry, urinary excretion rates of cortisol, cortisone and of various steroid metabolites were determined in 35 acromegalic patients (18 men, 17 women) and in 45 age- and weight-matched controls. The ratio of excreted cortisol/cortisone was similar in acromegalics (0.75 ± 0.20) and in controls (0.75 ± 0.24). Hence, the preponderance of the main cortisone-derived metabolite, tetrahydrocortisone, over the main metabolites of cortisol (tetrahydrocortisol and allotetrahydrocortisol; p < 0.01), which was seen both in female and in male acromegalics and which was directly correlated with the postglucose concentrations of growth hormone (r = 0.508, p < 0.01), suggests a decreased activity of 11β-hydroxysteroid dehydrogenase type 1 in acromegaly. Furthermore, the preponderance of etiocholanolone over androsterone (p < 0.01) in men (though not in women) with acromegaly – the ratio androsterone/etiocholanolone being negatively correlated with the serum concentrations of insulin-like growth factor type 1 (r = –0.406, p < 0.05) – suggests a relatively reduced activity of hepatic 5α-reductase in male acromegalics.