bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionic Surface Active Compounds in Atmospheric Aerosols
Authors: Sukhapan Jariya , Brimblecombe Peter
Published: March 2005

Surfactants in the atmosphere have several potential roles in atmospheric chemistry. They can form films on aqueous surfaces, which lowers the surface tension and possibly delays water evaporation and gaseous transportation across the aqueous interface. They can also increase the solubility of organic compounds in the aqueous phase. Recently, the decrease of surface tension in cloud growing droplets has been suggested as relevant to increases in the number of droplets of smaller size, potentially enhancing cloud albedo. Natural surfactants in the lung aid gas transfer and influence the dissolution rate of aerosol particles, so surfactants in atmospheric aerosols, once inhaled, may interact with pulmonary surfactants. Ambient aerosols were collected from the edge of Norwich, a small city in a largely agricultural region of England, and analysed for surfactants. Methylene blue, a conventional dye for detecting anionic surfactants, has been used as a colorimetric agent. The concentration of surfactants expressed as methylene blue active substances (MBAS) is in the range of 6–170 pmol m-3(air). A negative correlation with chloride aerosol indicates that these surfactants are probably not the well-known surfactants derived from marine spray. A more positive correlation with aerosol nitrate and gaseous NOxsupports an association with more polluted inland air masses. The surfactants found in aerosols seem to be relatively strong acids, compared with weaker acids such as the long-chain carboxylic acids previously proposed as atmospheric surfactants. Surfactants from the oxidation of organic materials (perhaps vegetation- or soil-derived) seem a likely source of these substances in the atmosphere.
Ischemia Elicits a Coordinated Expression of Pro-Survival Proteins in Mouse Myocardium
Authors: Lyn Deborah , Bao Shaojia , Bennett Nicole A. , Liu Xiaowei , Emmett Nerimiah L.
Published: March 2005

Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro-survival factors occur after myocardial ischemia. To gain an understanding of the factors involved with ischemic injury, we examined expression changes in pro-survival and opposing pro-apoptotic signals at early and chronic periods of ischemia using an in vivo murine model. Alterations of pro-survival proteins such as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic repressor protein (ARC) have not been evaluated in a murine model of cardiac ischemia. Early ischemia (1 day) resulted in a 50% reduction in ARC protein levels relative to sham-operated left ventricles, without significant changes in the expression of xIAP or other pro-survival factors. In contrast, a deficiency of xIAP expression was found in cardiac infarcts starting after 1 week, concomitant with significant evidence of apoptotic cell death and an up-regulation of pro-apoptotic signals including Bax, tumor necrosis factor-a, and caspase-8 activation. Chronic ischemia (after 2 weeks) was associated with elevated levels of other pro-survival factors such as Bcl-xLand the phosphorylated form of Akt, as part of the adaptive remodeling of the myocardium. Altogether, these findings suggest that strategies to increase IAP expression may promote myocyte survival after chronic ischemia.
Large-Scale Mapping and Predictive Modeling of Submerged Aquatic Vegetation in a Shallow Eutrophic Lake
Authors: Havens Karl E. , Harwell Matthew C. , Brady Mark A. , Sharfstein Bruce , East Therese L. , Rodusky Andrew J. , Anson Daniel , Maki Ryan P.
Published: March 2005

A spatially intensive sampling program was developed for mapping the submerged aquatic vegetation (SAV) over an area of approximately 20,000 ha in a large, shallow lake in Florida, U.S. The sampling program integrates Geographic Information System (GIS) technology with traditional field sampling of SAV and has the capability of producing robust vegetation maps under a wide range of conditions, including high turbidity, variable depth (0 to 2 m), and variable sediment types. Based on sampling carried out in AugustœSeptember 2000, we measured 1,050 to 4,300 ha of vascular SAV species and approximately 14,000 ha of the macroalga Chara spp. The results were similar to those reported in the early 1990s, when the last large-scale SAV sampling occurred. Occurrence of Chara was strongly associated with peat sediments, and maximal depths of occurrence varied between sediment types (mud, sand, rock, and peat). A simple model of Chara occurrence, based only on water depth, had an accuracy of 55%. It predicted occurrence of Chara over large areas where the plant actually was not found. A model based on sediment type and depth had an accuracy of 75% and produced a spatial map very similar to that based on observations. While this approach needs to be validated with independent data in order to test its general utility, we believe it may have application elsewhere. The simple modeling approach could serve as a coarse-scale tool for evaluating effects of water level management on Chara populations.
Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene
Authors: Zarain-Herzberg Angel , Alvarez-Fernandez Georgina
Published: March 2005

The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5’ -regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20 introns. The last two exons of the pre-mRNA produce by alternatively splicing the cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2 genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1 binding sites, and a thyroid hormone responsive element (TRE). There are two other conserved regulatory regions located between positions -410 to -661 bp and from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned. In addition, the human gene has several repeated sequences mainly of the Alu and L2 type located upstream from position -1.7 kb, spanning in a continuous fashion for more than 40 kb. In this study, we report the cloning of 2.4 kb of 5’-regulatory region and demonstrate that the proximal promoter region is sufficient for expression in cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA elements which down-regulate the expression of the SERCA2 gene in neonatal cardiomyocytes.
Biodegradation of Chlorsulfuron and Metsulfuron-Methyl byAspergillus niger
Authors: Zanardini Elisabetta , Negri Marco , Boschin Giovanna , D'Agostina Alessandra , Valle Anna , Arnoldi Anna , Sorlini Claudia
Published: March 2005

In this work, investigations were performed under laboratory conditions of the degradation ability by a common soil fungus,Aspergillus niger, toward chlorsulfuron and metsulfuron-methyl. The results were very encouraging (79% for chlorsulfuron and 61% for metsulfuron-methyl of total degradation), especially compared to those registered in our previous studies with a Pseudomonas fluorescens strain B2 (about 21 to 32%). Furthermore, the chemical degradation of the two compounds was studied and two products (1[2-methoxy-benzene-1-sulfonyl]-7-acetyltriuretand 1[2-chlorobenzene-1-sulfonyl]-7-acetyltriuret)were isolated and characterised by hydrolysis in acidic conditions. Our aim in the future will be the identification of intermediate metabolites by HPLC and LC-MS analyses in order to identify the degradative pathway by the fungal strain and to compare this to those obtained by chemical degradation and byP. fluorescens strain.
Variable Absorption of Clavulanic Acid After an Oral Dose of 25 mg/kg of Clavubactin® and Synulox® in Healthy Cats
Authors: Vree Tom B. , Dammers Eric , van Duuren Eri
Published: March 2005

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin® and formulation was B Synulox® ; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2= 1.24 ± 0.28 h, Cmax= 12.8 ± 2.12 μg/ml), and that of clavulanic acid 0.6 h (t1/2= 0.63 ± 0.16 h, Cmax= 4.60 ± 1.68 μg/ml). There is a ninefold variation in the AUCtof clavulanic acid for both formulations, while the AUCtof amoxicillin varies by a factor of two. The highest clavulanic acid AUCtvalues indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin–to–clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products’ high efficacy against susceptible microorganisms.
Molecular Binding Interactions: Their Estimation and Rationalization in QSARs in Terms of Theoretically Derived Parameters
Authors: Lewis David F.V. , Broughton Howard B.
Published: March 2005

An extensive survey of molecular binding interactions and parameters used in QSARs is reported, which includes consideration of lipophilicity and the derivation of Linear Free Energy Relationships associated with drug-receptor binding, together with an overview of the various contributions to binding energy. The lipophilic parameter, log P, and its relevance to desolvation energy is outlined and explanation of the parameters derived from electronic structure calculation is provided, leading into a summary of molecular dynamics simulations.
Mechanisms by which Human Cells Bypass Damaged Bases during DNA Replication after Ultraviolet Irradiation
Authors: Cleaver James E.
Published: March 2005

The replication of damaged DNA involves cascading mechanisms of increasing complexity but decreasing accuracy. The most accurate mechanism uses low-fidelity DNA polymerases, Pol H and Pol I, which have active sites sufficiently large to accommodate a pyrimidine dimer. Replicative bypass of DNA damage by these polymerases produces an accurately replicated, newly synthesized strand. Pol H negative cells (XP-V cell lines) either adopt a proposed secondary bypass mechanism or a recombinational mode. The mechanism of the secondary bypass is unclear, but a number of experiments suggests roles for excision repair to remove damage ahead of replication forks, hRad6/18 proteolysis to clear the blocked forks, and the Rad17-RFC and 9-1-1 complexes to establish a new replication apparatus. This alternative pathway requires functional p53. In Pol H negative cells in which p53 is also inactive, the arrested fork fragments into DNA double strand breaks. Foci containing PCNA, Mre11/Rad50/Nbs1, and gamma-H2Ax can then be detected, along with chromosomal rearrangement and high frequencies of sister chromatid exchanges. The recruitment of recombination components to the arrested forks represents the ultimate failure of replication machinery to relieve the arrested state and bypass the damage. The resulting chromosomal instability in surviving cells will contribute to malignant transformation.
Enhanced Hepatocarcinogenicity Due to Agonists of Peroxisome Proliferator-Activated Receptors in Senescent Rats: Role of Peroxisome Proliferation, Cell Proliferation, and Apoptosis
Authors: Youssef Jihan , Badr Mostafa
Published: March 2005

Exposure to agonists of peroxisome proliferator-activated receptor alpha (PPARα) causes liver cancer in rodents, with aged animals being more susceptible than their younger counterparts to this effect. Treatment with these chemicals produced a five- to sevenfold higher yield of grossly visible hepatic tumors in old rats compared to young animals. The enhanced susceptibility of the aged livers to the carcinogenic effect of PPAR agonists could not be explained by differences in levels of peroxisomal and/or cell proliferation between young and old animals, as neither of these responses was exaggerated with aging. Reported studies have shown that activating PPARa results in the suppression of hepatic apoptosis. This effect is expected to diminish the ability of the liver to purge itself of pre-existing neoplastic cells, allowing them to progress to tumors. New findings from our laboratories show that the aged liver is exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition, aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2 than livers of young, adult, and middle-aged animals. Interestingly, the PPARa agonist Wy-14,643 significantly diminished elements of the proapoptotic machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably increasing elements of this machinery in younger animals. Taken together, while activation of PPARs appears to inhibit apoptosis in livers of senescent animals, activating these receptors seems to stimulate the apoptotic machinery in young animals. This paradoxical effect may be responsible for the exaggerated sensitivity of the aged liver to the carcinogenic effect of agents that activate PPARs.
Carbon Reservoirs in Temperate South American Nothofagus Forests
Authors: Baswald Klaus , Lencinas Jose D. , Loguercio Gabriel
Published: March 2005

Humans are influencing the global carbon (C) cycle due to the combustion of fossil fuels and due to changes in land use management. These activities are fostering the manmade greenhouse effect and thus global climate change. Negative effects for life on earth are accounted for.

Among others the international climate debate focused attention on forests and forestry, knowing about their considerable influence on global climate change. Whilst the global C budget is described fairly well, there is a lack of regional data describing the C reservoirs and flows in detail. This has to be constituted especially for forests in developing countries.

This paper presents an investigation at regional scale of the C reservoirs in a South American forest ecosystem. The investigation puts emphasis on the area and stand volume estimation and the development of expansion and reduction factors. Vegetation types are classified and stratified, determining the corresponding areas and estimating the stand volume. Converting factors are developed to calculate C in branches and roots as a percentage of standing wood measured by inventories.
Epithelial Cell-Neutrophil Interactions in the Alimentary Tract: A Complex Dialog in Mucosal Surveillance and Inflammation
Authors: Colgan Sean P. , Comerford Katrina M. , Lawrence Donald W.
Published: March 2005

Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and intestine, inevitably require the intimate interactions of neutrophils with columnar epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets for the treatment of mucosal inflammation. Elegantin vitromodel systems incorporating purified human neutrophils and human epithelial cells grown in physiologic orientations have aided in discovery of new and insightful pathways to define basic inflammatory pathways. Here, we will review the recent literature regarding the interactions between columnar epithelial cells and neutrophils, with an emphasis on intestinal epithelial cells, structural aspects of neutrophil transepithelial migration, molecular determinants of neutrophil-epithelial cell interactions, as well as modulation of these pathways. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.
Lipid-Derived Mediators in Endogenous Anti-Inflammation and Resolution: Lipoxins and Aspirin-Triggered 15-epi-Lipoxins
Authors: Serhan Charles N. , Chiang Nan
Published: March 2005

It is well appreciated that lipid-derived mediators play key roles in inflammation and many other physiologic responses where multicellular processes are involved. Among them, lipoxins (LX) and aspirin-triggered LX (ATL) evoke actions of interest in a range of physiologic and pathophysiologic processes, and these two series have emerged as founding members of the first class of lipid/chemical mediators “switched on” in the resolution phase of an inflammatory reaction. These unique compounds possess a trihydroxytetraene structure and are both structurally and functionally distinct among the many groups of lipid-derived bioactive mediators. LXA4 and 15-epi-LXA4(a member of the ATL series) display leukocyte-selective actions that enable them to serve as endogenous “stop signals” in multicellular events in that they modulate adherence, transmigration, and chemotaxis. Both LXA4and 15-epi-LXA4elicit these responses via a G protein-coupled receptor (GPCR), termed ALXR, identified in human and murine tissues. Among eicosanoids, ALXR is stereoselective for LXA4(5S,6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid). Its aspirin-triggered 15R epimer (15-epi-LXA4) and their bioactive stable analogs act in the subnanomolar to nanomolar range in human cellular systems and murine models of acute inflammation and reperfusion. ALXR also has the ability to interact with a wide panel of small peptides that give different signaling responses in vitro than LXA4or its analogs, suggesting that ALXR is capable of serving as a multirecognition receptor in immune responses. Characterization of ALXR and development of metabolically stable LX and ATL analogs that are mimetics rapidly advanced our appreciation of the mechanism of LX actions and the potential utility of these counter-regulatory biocircuits in the quest to control local inflammatory events. In this on-line update, LX and ATL biosynthesis and the LXA4specific receptor, termed ALXR, are reviewed with a focus on their roles in inflammation and resolution with respect to pharmacology, molecular biology, and signal transduction in several cell types and animal models investigated thus far.
Polychlorinated Alkanes in Fish from Norwegian Freshwater
Authors: Borgen Anders R. , Schlabach Martin , Kallenborn Roland , Fjeld Eirik
Published: March 2005

Short-chain polychlorinated alkanes (sPCAs) have been measured in freshwater fish samples from different lakes all over Norway and from the Norwegian Arctic. The analyses were performed with high-resolution GC coupled to high-resolution MS in electron capture negative ion mode. The species investigated were trout, Arctic char, and burbot (Lota lota). Muscle tissue in the lake trout and Arctic char, and liver in burbot, were selected for analyses because of their high lipid content. ∑sPCA concentration ranged from 108 to 3700 ng/g fat. The highest value was found in the south of Norway near an industrial area.
Climatic Impact of Volcanic Eruptions
Authors: Zielinski Gregory A.
Published: March 2005

Volcanic eruptions have the potential to force global climate, provided they are explosive enough to emit at least 1–5 megaton of sulfur gases into the stratosphere. The sulfuric acid produced during oxidation of these gases will both absorb and reflect incoming solar radiation, thus warming the stratosphere and cooling the Earth’s surface. Maximum global cooling on the order of 0.2–0.3°C, using instrumental temperature records, occurs in the first 2 years after the eruption, with lesser cooling possibly up to the 4th year. Equatorial eruptions are able to affect global climate, whereas mid- to high-latitude events will impact the hemisphere of origin. However, regional responses may differ, including the possibility of winter warming following certain eruptions. Also, El Niño warming may override the cooling induced by volcanic activity. Evaluation of different style eruptions as well as of multiple eruptions closely spaced in time beyond the instrumental record is attained through the analysis of ice-core, tree-ring, and geologic records. Using these data in conjunction with climate proxy data indicates that multiple eruptions may force climate on decadal time scales, as appears to have occurred during the Little Ice Age (i.e., roughly AD 1400s–1800s). The Toba mega-eruption of ~75,000 years ago may have injected extremely large amounts of material into the stratosphere that remained aloft for up to about 7 years. This scenario could lead to the initiation of feedback mechanisms within the climate system, such as cooling of sea-surface temperatures. These interacting mechanisms following a mega-eruption may cool climate on centennial time scales.
Purification of Intact Plant Protoplasts by Flotation at 1g
Authors: Graham John
Published: March 2005

From a standard plant tissue digest adjusted to a density of 1.07 g/ml, protoplasts can be harvested by flotation through a low density barrier (1.03 g/ml). The delicate nature of these bodies is suited to this flotation strategy which can be carried out at 1g.
Isolation of a Mouse Motoneuron-Enriched Fraction from Mouse Spinal Cord on a Density Barrier
Authors: Graham John
Published: March 2005

After a combined enzymic and mechanical disruption of the spinal cord tissue, the low-density motoneurons band at the interface of a 1.06-g/ml barrier through which other contaminating cells sediment.
Homogenization of Mammalian Cultured Cells
Authors: Graham John
Published: March 2005

Satisfactory homogenization of cultured cells is a necessary prerequisite to any fractionation schedule. Protocols are given for homogenization in iso-osmotic (A) and hypo-osmotic (B) media that should be broadly applicable to any cell type and to any subsequent fractionation procedure. Alternative procedures are also summarized in the Notes section, but detailed operation of some of the automated devices is beyond the scope of this short Protocol Article.
Homogenization of Mammalian Tissues
Authors: Graham John
Published: March 2005

Satisfactory homogenization of a tissue is a necessary prerequisite to any fractionation schedule. A detailed protocol is given for rat liver because of the widespread use of this tissue. Although this technique should be broadly applicable to any soft tissue and to any subsequent fractionation procedure, there are certain tissues and applications that require either minor or extensive modification. Some of these points are addressed in the Notes section.
The Fas/FasL System in Reproduction: Survival and Apoptosis
Authors: Mor Gil , Straszewski Shawn , Kamsteeg Marijke
Published: March 2005

For centuries, the question of “whether there is life after death” has intrigued the mind of philosophers, and the same question fascinates researchers in the field of apoptosis today. The death of a cell is by no means the end of the story. On the contrary, growing evidence suggests that the clearance of apoptotic bodies by macrophages is an important regulatory component in tissue renewal. Without death by apoptosis, the life of reproductive tissues and their function would not be possible. The survival signals that counteract cell death also prepare the cells for apoptosis, and dead cells are important stimuli for tissue survival. The Fas/FasL system is an important mediator in apoptosis and is and excellent example of this apparently contradictory phenomenon.
Evolutionary Theories of Aging and Longevity
Authors: Gavrilov Leonid A. , Gavrilova Natalia S.
Published: March 2005

The purpose of this article is to provide students and researchers entering the field of aging studies with an introduction to the evolutionary theories of aging, as well as to orient them in the abundant modern scientific literature on evolutionary gerontology. The following three major evolutionary theories of aging are discussed: 1) the theory of programmed death suggested by August Weismann, 2) the mutation accumulation theory of aging suggested by Peter Medawar, and 3) the antagonistic pleiotropy theory of aging suggested by George Williams. We also discuss a special case of the antagonistic pleiotropy theory, the disposable soma theory developed by Tom Kirkwood and Robin Holliday. The theories are compared with each other as well as with recent experimental findings. At present the most viable evolutionary theories are the mutation accumulation theory and the antagonistic pleiotropy theory; these theories are not mutually exclusive, and they both may become a part of a future unifying theory of aging.

Evolutionary theories of aging are useful because they open new oppor-tunities for further research by suggesting testable predictions, but they have also been harmful in the past when they were used to impose limitations on aging studies. At this time, the evolutionary theories of aging are not ultimate completed theories, but rather a set of ideas that themselves require further elaboration and validation. This theoretical review article is written for a wide readership.
Apoptosis Gene Hunting Using Retroviral Expression Cloning: Identification of Vacuolar ATPase Subunit E
Authors: Anderson Claire L. , Williams Gwyn T.
Published: March 2005

Over the past 10-15 years there has been an explosion of interest in apoptosis. The delayed realisation that cell death is an essential part of life for any multicellular organism has meant that, despite the recent and rapid developments of the last decade, the precise biochemical pathways involved in apoptosis remain incomplete and potentially novel genes may, as yet, remain undiscovered. The hunt is therefore on to bridge the remaining gaps in our knowledge. Our contribution to this research effort utilises a functional cloning approach to isolate important regulatory genes involved in apoptosis. This mini-review focuses on the use and advantages of a retroviral expression cloning strategy and describes the isolation and identification of one such potential apoptosis regulatory gene, namely that encoding vacuolar ATPase subunit E.
Quality of Life Philosophy IV. The Brain and Consciousness
Authors: Ventegodt Søren , Andersen Niels Jørgen , Merrick Joav
Published: March 2005

In this article we look at the brain’s structure and function from a philosophical perspective. Although the brain at micro-level, with its trillions of ultra-thin nerve fibers, is one of the most complicated structures in the known universe, you can still grasp its composition if you go up to the level of the cell. How this structure functions is not quite clear. You can understand its function at fiber level, because it is fairly simple, and you can understand it at cell level, but it is already vague. Roughly speaking, you can envision a single nerve cell as a tiny, independent computer whose behavior is dependent on continuous calculations of all input. At organ level, the function can be understood as an extremely complex pattern machine. Finally, the brain’s function can be understood at the cognitive level as what provides consciousness through its ability to keep order in our complicated reality. The superior function of the brain is to connect the real us, our higher self, to the surrounding world.The brain has been developed so that it can create all possible complex patterns. The connectivity seems to imply that the patterns of the human brain are 1000-dimensional. It is our vision that these complicated patterns arise from basic patterns in the quantum matter of which everything is created. In our opinion, our consciousness’ special utilization of a patterned aspect of nature is what lies behind inscrutable statements like “Man is created in God’s image”. We suggest that these patterns in matter are the basic, creative force that influences all living organisms. Unfortunately, science has only just begun to understand these patterns.The Bible’s description of the origin of man is two people eating from the Tree of Knowledge and as punishment they are expelled from the Garden of Eden. What does that mean? It means that, as conscious creatures, we no longer were an unproblematic, harmonious part of the world around us. The great question is why this consciousness about the world, provided by the brain, is not a gift that makes life better instead of getting us expelled from the Garden of Eden. We think that our real problem is the fact that we are still not in control of our consciousness. Instead of it serving us, we have become its slaves. If we come to understand brain and consciousness in order to solve this basic problem of our existence, we shall again be able to become a coherent part of the world, both as individuals and as a species. We share the vision that such an understanding of the problems of consciousness will make medical science holistic and will bring quality of life, health, and the ability to function to its patients.
Quality of Life Philosophy V. Seizing the Meaning of Life and Becoming Well Again
Authors: Ventegodt Søren , Andersen Niels Jørgen , Merrick Joav
Published: March 2005

This paper presents a positive philosophy of life developed to support and inspire patients to take more responsibility for their own lives and to draw more efficiently on their known or hidden resources. The idea is that everybody can become wiser, use themselves better, and thus improve quality of life, subjective health, and the ability to function.To be responsible means to see yourself as the cause of your own existence and state of being. To be the one who forms your own life to your liking, so that others do not shape it in the way they prefer to see you. Seen this way, taking responsibility in practice is one of the most difficult things to do. One of the greatest and most difficult things to do in this context is to be able to love. To be the one who loves, instead of being the one who demands love, care, awareness, respect, and acceptance from somebody else.Since almost all of us have had parents who maybe loved us too little and mostly conditionally, we all harbor a deep yearning to be loved as we are, unconditionally. A lot of our energy is spent trying to find recognition and acceptance, more or less as we did as children from our parents, who created the framework and defined the rules of the game. But today, reality is different. We have grown up and now life is about shaping our own existence. So we must be the ones who love. This is what responsibility is all about. Taking responsibility is, quite literally, moving the barriers in our lives inside ourselves. Taking responsibility for life means that you are willing to see that the real barriers are not all these external ones, but something that can be found within yourself. Of course there is an outside world that cannot be easily shaped according to your dreams. But a responsible point of view is that although it is difficult, the problem is not impossible; it is your real challenge and task. If there is something you really want, you can achieve it, but whether it happens depends on your wholehearted, goal-oriented, and continuous attempts. This paper describes the philosophy about seizing the meaning of life and becoming well again, even when there is little time left.
Iodixanol Development of a Laboratory-Scale Technique to Monitor the Persistence of Mycobacterium avium subsp. paratuberculosis in Cheddar Cheese
Authors: Donaghy J. A. , Totton N. L. , Rowe M. T.
Published: March 2005

Mycobacterium avium subsp. paratuberculosis (Map) is a potential human pathogen known to be present in raw milk from infected dairy herds. Current pasteurisation regimes do not totally inactivate Map resulting in the possibility of viable cells being present in pasteurised milk used for Cheddar cheese production. A laboratory-based method, ensuring strict safety precautions, was developed to manufacture 800-g Cheddar blocks, experimentally contaminated (postpasteurisation) with two different strains of Map. The composition of the model Cheddar produced was consistent with commercial product. Syneresis of the cheese curd caused a 1 log10 concentration of Map numbers from milk to cheese for a strain isolated from pasteurised milk. The type strain NCTC 8578 did not show a similar concentration effect, but did however survive the Cheddar manufacturing process. A small percentage (<5%) of the Map load for each strain was recovered in the whey fraction during the process.
Quality of Life Philosophy II: What is a Human Being?
Authors: Ventegodt Søren , Andersen Niels Jørgen , Kromann Maximilian , Merrick Joav
Published: March 2005

The human being is a complex matter and many believe that just trying to understand life and what it means to be human is a futile undertaking. We believe that we have to try to understand life and get a grip on the many faces of life, because it can be of great value to us to learn to recognize the fundamental principles of how life is lived to the fullest. Learning to recognize the good and evil forces of life helps us to make use of the good ones.To be human is to balance between hundreds of extremes. Sometimes we have to avoid these extremes, but at other times it seems we should pursue them, to better understand life. With our roots in medicine, we believe in the importance of love for better health. The secret of the heart is when reason and feelings meet and we become whole. Where reason is balanced perfectly by feelings and where mind and body come together in perfect unity, a whole new quality emerges, a quality that is neither feeling nor reason, but something deeper and more complete.In this paper, we outline only enough biology to clarify what the fundamental inner conflicts are about. The insight into these conflicts gives us the key to a great deal of the problems of life. To imagine pleasures greater than sensual pleasures seems impossible to most people. What could such a joy possibly be? But somewhere deep in life exists the finest sweetness, the greatest quality in life, the pure joy of being alive that emerges when we are fully present and life is in balance. This deep joy of life is what we call experiencing the meaning of life.
The Life Mission Theory II. The Structure of the Life Purpose and the Ego
Authors: Ventegodt Soren , Andersen Niels Jorgen , Merrick Joav
Published: March 2005

Pursuing your life mission is often very difficult, and many frustrations are experienced along the way. Major failures to bring out our potential can cause us considerable emotional pain. When this pain is unbearable, we are induced to shift from one intention and talent to another that better allows us to adapt and survive. Thus, we become set on a course that brings out a secondary or tertiary talent instead of the primary talent. This talent displacement may be expressed as a loss of our true nature or true self. The new purpose in life now functions as the core of a new personality: the ego. The ego has a structure similar to that of the true self. It is anchored in a talent and it draws on subtalents. But the person who is centered in his or her ego is not as powerful or talented as the person he or she originally was, living the primary purpose of life. This is because the original personality (the true self or “higher self”) is still there, active and alive, behind the ego. Symptoms, disorders, and diseases may be explained by the loss of energy, joy in life, and intuitive competence because of inner conflicts, which may be alleviated or cured in the salutogenetic process of Antonovsky that helps patients find their sense of coherence or their primary purpose in life. Many cases of reduced ability to function, physically as well as psychologically, socially or sexually, can also be explained and alleviated in this way. When a person discovers his true talent and begins to use it with dedication, privately as well as professionally, his life will flourish and he may overcome even serious disease and great adversity in life. The salutogenetic process can also be called personal development or “quality of life as medicine”. It is important to note that the plan for personal development laid out by this theory is a plan not for the elimination of the ego, but for its cultivation. An existentially sound person still has a mental ego of course, but it is centered on the optimal verbal expression of the life mission. Such an ego is not in conflict with one�s true self, but supports the life and wholeness of the person, although in an invisible and seamless way. The more developed the person, the more talents are taken into use. So although the core of existence remains the same throughout life, the healthy person continues to grow. As the number of talents we can call on is unlimited, the journey ends only at death. Understanding the concept of the ego, it is very easy for the physician to motivate the patient to go through a lot of difficulties in order to grow and develop, and when the patient fully understands the concept of the ego and the true self (higher self), the patient gets a strong feeling of direction in personal development, and a motivation to fight the internal obstacles for quality of life, health, and the ability to function.
The Life Mission Theory V. Theory of the Anti-Self (the Shadow) or the Evil Side of Man
Authors: Ventegodt Soren , Andersen Niels Jorgen , Merrick Joav
Published: March 2005

According to the life mission theory, the essence of man is his purpose of life, which comes into existence at conception. This first purpose is always positive and in support of life. This is not in accordance with the everyday experience that man also engages in evil enterprises born out of destructive intentions. This paper presents a theory about the evil side of man, called the �anti-self� (the shadow), because it mirrors the self and its purpose of life. The core of the anti-self is an evil and destructive intention opposite to the intention behind the life mission. The evil side of man arises when, as the life mission theory proclaims, man is denying his good, basic intention to avoid existential pain. The present theory of the anti-self claims that all the negative decisions accumulated throughout the personal history, sum up to a negative or dark anti-self, as complex, multifaceted, and complete as the self. All the negative decisions taken through personal history build this solid, negative, existential structure. The anti-self, or shadow as Carl Gustav Jung used to call it, is a precise reflection of man�s basically good and constructive nature. When mapped, it seems that for most or even for all the many fine talents of man, there is a corresponding evil intention and talent in the person�s anti-self. As man is as evil as he is good, he can only realize his good nature and constructive talents by making ethical choices. Ethics therefore seem to be of major importance to every patient or person engaged in the noble project of personal growth. Understanding the nature and structure of the evil side of man seems mandatory to every physician or therapist offering existential therapy to his patient. The theory of anti-self makes it possible to treat patients with destructive behavioral patterns, who want to be good deep in their heart, by helping them let go of their evil intentions. The anti-self also seems to explain the enigma of why human beings often commit suicide. Integrating the shadow often leads to dramatic, subjective experiences of ubiquitous light in an �unpersonal� form, of enlightenment, or of meeting light and consciousness in a personal, universal form, known as G-d.
Differences Between Lovastatin and Simvastatin Hydrolysis in Healthy Male and Female Volunteers: Gut Hydrolysis of Lovastatin is Twice that of Simvastatin
Authors: Vree Tom B. , Dammers Erik , Ulc Ivan , Horkovics-Kovats Stefan , Ryska Miroslav , Merkx IJsbrand
Published: March 2005

The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-β-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: 1-The group of female volunteers showed a higher yield of the active metabolite β-hydroxy acid than the group of males (p < 0.002) for both lovastatin and simvastatin. This difference was not related to the body weight of both groups. 2-In the male/female groups, subject-dependent yield of active metabolite β-hydroxy acid was demonstrated, which was independent of the formulation. The variation in plasma/liver hydrolysis resulted in a fan-shaped distribution of data points when the AUCtlovastatin was plotted vs. that of the β-hydroxy acid metabolite. In the fan of data points, subgroups could be distinguished, each showing a different regression line and with a different Y-intercept (AUCtβ-hydroxy acid). 3-Lovastatin hydrolysis was higher than simvastatin hydrolysis. 4-It was possible to discriminate between hydrolysis of both lovastatin and simvastatin by plasma/liver or tissue esterase activity.

The three subgroups of subjects (males/females) showing different but high yield of statin β-hydroxy acid can be explained by variable hydrolysis of plasma and hepatic microsomal and cytosolic carboxyesterase activity.

This study showed clearly that despite the subject-dependent hydrolysis of lovastatin/simvastatin to the active metabolite, males tend to hydrolyse less than females. The extra methyl group in simvastatin results in less hydrolysis due to steric hindrance.
Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared
Authors: Chun Paul
Published: March 2005

We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(T)reactionleads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0) is 7.53 kcal mol-1compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0) in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0), and provides for better understanding of the heat of reaction for biological molecules.
Molluscan Shell Matrix Characterization by Preparative SDS-PAGE
Authors: Marin Frederic
Published: March 2005

The glycoproteinaceous constituents of molluscan shell matrices usually resist chromatographical fractionation. We describe a protocol that overcomes this difficulty and permits collection of a large amount of shell proteins for further in vitro characterization. After dissolution of the mineral phase, the glycoproteins are fractionated �blind� on a preparative electrophoresis. They are subsequently detected with a polyclonal antibody raised against the whole matrix.
Synthesis of Platinum Complexes from N-Benzyl-2-Aminoethanethiol Derivatives
Authors: de Almeida Mauro Vieira , de Oliviera Laura Lúcia C. , Cesar Eloi Teixeira , de Souza Marcus Vinícius N.
Published: March 2005

Twelve new platinum(II) complexes, analogs of cisplatin, containing a 2-aminoethanethiol N-substituted by several benzyl groups have been prepared and characterized in good yields. The ligands were obtained by reaction between 2-aminoethanethiol hydrochloride and different benzyl halides
Quality of Life as Medicine: A Pilot Studyof Patients with Chronic Illness and Pain
Authors: Ventegodt Soren , Merrick Joav , Anderson JØrgen
Published: March 2005

An intensive 5-day quality-of-life (QoL) session was constructed based on a psychosomatic model. The session was comprised of teaching on philosophy of life, psychotherapy, and body therapy. The three elements were put together in such a way that they mutually supported each other. The synergy attained was considerable. The pilot study demonstrated that in the course of only 1 week, patients had time to revise essential life-denying views and to integrate important, unfinished life events involving negative feelings. Consequently, the patients became more present in the body’s blocked-off areas and subjectively healthier. Nineteen persons with chronic illness and pain (fibromyalgia, chronic tiredness, whiplash, mild depression, and problems involving pain in arms and legs including osteoarthritis), and unemployed for 5–7 years attended the course. In the week before and after the 5-day course, the participants completed the validated SEQOL (Self-Evaluation of Quality of Life Questionnaire) including questions on self-evaluated health and the unvalidated “Self-Evaluation of Working-Life Quality Questionnaire” (SEQWL). This pilot study was without a control group or clinical control. As far as diagnoses were concerned, the group was inhomogeneous. Common for the group was a low QoL, poor quality of working life QWL, and numerous health problems. The study showed an 11.2% improvement in QoL (p< 0.05), a 6.3% improvement in QWL (p< 0.05), and a 12.0% improvement in self-perceived physical health (p= 0.08). There was a 17.3% improvement in self-perceived psychological health (p< 0.05) and satisfaction with health in general improved by 21.4% (p< 0.05). Symptoms like pain were almost halved and several of the participants were free of pain for the first time in years. In conclusion it seemed that the combination of training in philosophy of life, psychotherapy, and body therapy can give patients a large, fast, and efficient improvement in QoL, QWL, and health. It is not known if these changes will be permanent and if all kinds of patients with different health problems will gain from this cure. Further research should be conducted.
Molecular Packing in Network-Forming Collagens
Authors: Knupp Carlo , Squire John M.
Published: March 2005

Collagen is the most abundant protein among vertebrates and occurs in virtually all multicellular animals. Collagen molecules are classified into 21 different types and differ in their sequence, weight, structure, and function, but they can be broadly subdivided into families. Type IV, VI, VIII, X, and dogfish egg case collagens belong to the network-forming family. Here, we summarise what is known about the way these collagen molecules pack to form networks. In addition the main structural characteristics of the network-forming collagens are compared and discussed.