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At least 181 records · Page 10Linked to original sources
PubMed2002

The immune system: a weapon of mass destruction invented by evolution to even the odds during the war of the DNAs.

Living systems operate under interactive selective pressures. Populations have the ability to anticipate the future by generating a repertoire of elements that cope with new selective pressures. If the repertoire of such elements were transcendental, natural selection could not operate because any one of them would be too rare. This is the problem that vertebrates faced in order to deal with a vast number of pathogens. The solution was to invent an immune system that underwent somatic evolution. This required a random repertoire that was generated somatically and divided the antigenic universe into combinatorials of determinants. As a result, it became virtually impossible for pathogens to escape recognition but the functioning of such a repertoire required two new regulatory mechanisms: 1) a somatic discriminator between Not-To-Be-Ridded ('Self') and To-Be-Ridded ('Non-self') antigens, and 2) a way to optimize the magnitude and choice of the class of the effector response. The principles governing this dual regulation are analyzed in the light of natural selection.

Animals↗
PubMed2003

Evolving controllers for a homogeneous system of physical robots: structured cooperation with minimal sensors.

We report on recent work in which we employed artificial evolution to design neural network controllers for small, homogeneous teams of mobile autonomous robots. The robots were evolved to perform a formation-movement task from random starting positions, equipped only with infrared sensors. The dual constraints of homogeneity and minimal sensors make this a non-trivial task. We describe the behaviour of a successful system in which robots adopt and maintain functionally distinct roles in order to achieve the task. We believe this to be the first example of the use of artificial evolution to design coordinated, cooperative behaviour for real robots.

Adaptation, Physiological↗
PubMed2005

Aposematism: what should our starting point be?

The evolution of aposematism is considered to be a major evolutionary problem because if new aposematic forms emerged in defended cryptic populations, they would face the dual problems of rarity and conspicuousness. We argue that this commonly assumed starting point might not have wide validity. We describe a novel evolutionary computer model in which prey evolve secondary defences and become conspicuous by moving widely over a visually heterogeneous habitat. Unless crypsis imposes high opportunity costs (for instance, preventing prey from efficient foraging, thermoregulation and communication), costly secondary defences are not predicted to evolve at all. However, when crypsis imposes opportunity costs, prey evolve secondary defences that facilitate raised behavioural conspicuousness as prey exploit opportunities within their environment. Optimal levels of secondary defence and of behavioural conspicuousness increase with population sizes and the costs imposed by crypsis. When prey are already conspicuous by virtue of their behaviours, the evolution of aposematic appearances (bright coloration, etc.) is much easier to explain because aposematic traits add little further costs of conspicuousness, but can bring large benefits.

Adaptation, Physiological↗
PubMed2000

Evaluation of the acute scarring response to the implant of different types of biomaterial in the abdominal wall.

Since the short-term, acute scarring process induced by a biomaterial may condition the evolution of the repair process, the present investigation evaluates the behavior of polytetrafluoroethylene (PTFE) and polypropylene (PL) biomaterials in the initial stages of repair. Three PTFE biomaterials (Mycro Mesh, Dual Mesh and Soft Tissue Patch) and one PL biomaterial (Marlex) were employed to repair defects created in the abdominal wall of New Zealand rabbits. Animals were sacrificed at 3 or 7 days. Specimens were obtained for light and scanning electron microscopy, and immunohistochemical analysis using the RAM-11 monoclonal antibody for rabbit macrophages. The PL implants showed substantial adhesion formation with viscera. Lower adhesion formation was detected in the PTFE implants. The evolution of the acute phase of the repair process was similar for each PTFE biomaterial. At 3 days post implant, an incipient neoperitoneum was detected which was fully established after 7 days. The behavior of the PL implant was similar, although a greater amount of reticular granulation was detected. The neoformed peritoneum was irregular. Few RAM-11-labeled macrophages were detected in all cases. The acute phase of the tissue repair process induced by the implant of PTFE and PL biomaterials generally proceeds along similar lines to a normal repair process. However, the use of microporous, laminar materials seems to favor the early establishment of a well-defined neoperitoneal layer.

Journal Article↗
PubMed1984

Meal to meal energy balance in rats.

Meal to meal energy balance was examined in thirty-eight simultaneous recordings of feeding pattern and O2 consumption in six rats. The mean difference between energy intake in a meal and energy expenditure until the onset of the next meal was found positive at night and negative during day time. At night the excess of meal intake over meal to meal expenditures was decreasing from the beginning to the end of the night and was strongly correlated to meal sizes. During day time meal to meal deficit was decreasing from the beginning to the end of the period but was not correlated to meal sizes. These meal location and size effects on the meal to meal energy balance were not determined by an effect of these factors on metabolic rate. No indication was provided that meal to meal energy balance was influenced by a "meal induced thermogenesis." Rather an evolution from the beginning to the end of the night of the correlation between meal size and durations of meal to meal intervals was found to be parallel to the evolution of positive meal to meal energy balance throughout the night. From these data it is concluded that at night a dual utilization of meal caloric intake (current energy metabolism plus fat storage) and a dual source of fuel during the day (food plus mobilized fats) determine time and mechanism of meal onset.

Animals↗
PubMed1982

[Case summaries in real-time. Accomplishments with a microcomputer].

A study of the key wordings used by the doctors in medical records in I.C.U. preceded this implementation, they constitute a thesaurus (2,700 strings) organized in two trees. These strings are proposed along the dialogue which occurs between the microcomputer and the user; on these bases, several graphs allow to move in the tree by minimization of the pathway. The use of the thesaurus with the corresponding graphs necessitates only one automaton program. This medical data microcomputerized system is transparent for the user, thanks to a multilayers software. In the external layer the microcomputer provides access to the system by one of the following function keys: creation of a medical record, additional information on a medical record already known, research of a medical record, listing of the open medical records, printing of a medical record. Each one of these function keys provides access to the following five rubrics keys: identity, antecedents, reasons for admission, evolution, destiny; these rubric keys use parameterized procedures. This software is implemented on a low-cost microcomputer fitted with a dual drive disk (170 k. bytes each) and a printer (90 char/s).

Computers↗
PubMed2006

Global tuning of local molecular phenomena: an alternative approach to bionanoelectronics.

We have applied simultaneous horizontal and vertical bias to a single molecule (2 nm(2)) in an ordered and disordered matrix to virtually isolate and tune its property without taking it out physically from its environment. Using a dedicated electrode system, we have locally tuned nanoscale properties vertically by STM, while stabilizing its environment by applying a global electric field horizontally. Using this technique, we report tuning of molecular conformations in room temperature, whose evolution of states has been statistically investigated. We have also shown control on switching of a few selected conformations by applying dual bias simultaneously. As we avoid any direct injection of charge into the system via electrode contact, this technique could be used as a generalized method to tune phenomena evolved in an environment of weak interaction from a large distance without destroying the property.

Electrochemistry↗
PubMed2000

Immunobiology of persistent blood-borne viral infections.

Host-virus interactions have co-evolved to play an interactive role in the pathogenesis of viral infections and their disease outcome. Host responses to viral infections, including the cell-mediated and humoral immune responses, have been a subject of intensive research in virology and immunology. Definition of specific cellular receptors for cellular entry of the agents, the rates of their intracellular viral replication, the rates of turnover of circulating virions, persistence of viral infection possibly due to inadequate immune responses, and continued formation of circulating immune complexes provide the framework for our current understanding of the immunopathology of virally induced disease. Among the multiple blood-borne viruses (BBV) transmissible through transfusion, hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV-1/-2) are relatively more important than several other viruses. Not only do they establish asymptomatic persistent infections with occasional oncogenic sequelae, but they also cause significant morbidity and mortality when transmitted through transfusion of blood and blood products. Molecular characterization of these agents and their in vitro inactivation and removal from blood have become key issues in contemporary transfusion safety since the advent of AIDS. Because many of the BBV are associated with white blood cells that have no therapeutic benefit in haemotherapy, simple filtration-removal of leukocytes from donated blood confers a dual benefit of immunological and virological safety in transfusion medicine.

Biological Evolution↗
PubMed2004

Sensors for rate responsive pacing.

Advances in pacemaker technology in the 1980s have generated a wide variety of complex multiprogrammable pacemakers and pacing modes. The aim of the present review is to address the different rate responsive pacing modalities presently available in respect to physiological situations and pathological conditions. Rate adaptive pacing has been shown to improve exercise capacity in patients with chronotropic incompetence. A number of activity and metabolic sensors have been proposed and used for rate control. However, all sensors used to optimize pacing rate metabolic demands show typical limitations. To overcome these weaknesses the use of two sensors has been proposed. Indeed an unspecific but fast reacting sensor is combined with a more specific but slower metabolic one. Clinical studies have demonstrated that this methodology is suitable to reproduce normal sinus behavior during different types and loads of exercise. Sensor combinations require adequate sensor blending and cross checking possibly controlled by automatic algorithms for sensors optimization and simplicity of programming. Assessment and possibly deactivation of some automatic functions should be also possible to maximize benefits from the dual sensor system in particular conditions. This is of special relevance in patient whose myocardial contractility is limited such as in subjects with implantable defibrillators and biventricular pacemakers. The concept of closed loop pacing, implementing a negative feedback relating pacing rate and the control signal, will provide new opportunities to optimize dual-sensors system and deserves further investigation. The integration of rate adaptive pacing into defibrillators is the natural consequence of technical evolution.

Journal Article↗
PubMed2004

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution.

While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the identification of novel selenoprotein genes. Here, we describe a comparative genomics approach that relies on the genome-wide prediction of genes with in-frame TGA codons, and the subsequent comparison of predictions from different genomes, wherein conservation in regions flanking the TGA codon suggests selenocysteine coding function. Application of this method to human and fugu genomes identified a novel selenoprotein family, named SelU, in the puffer fish. The selenocysteine-containing form also occurred in other fish, chicken, sea urchin, green algae and diatoms. In contrast, mammals, worms and land plants contained cysteine homologues. We demonstrated selenium incorporation into chicken SelU and characterized the SelU expression pattern in zebrafish embryos. Our data indicate a scattered evolutionary distribution of selenoproteins in eukaryotes, and suggest that, contrary to the picture emerging from data available so far, other taxa-specific selenoproteins probably exist.

Amino Acid Sequence↗
PubMed2002

The serpin SQN-5 is a dual mechanistic-class inhibitor of serine and cysteine proteinases.

SQN-5 is a mouse serpin that is highly similar to the human serpins SCCA1 (SERPINB3) and SCCA2 (SERPINB4). Previous studies characterizing the biochemical activity of SQN-5 showed that this serpin, like SCCA2, inhibited the chymotrypsin-like enzymes mast cell chymase and cathepsin G. Using an expanded panel of papain-like cysteine proteinases, we now show that SQN-5, like SCCA1, inhibited cathepsins K, L, S, and V but not cathepsin B or H. These interactions were characterized by stoichiometries of inhibition that were nearly 1:1 and second-order rate constants of >10(4) M(-1) s(-1). Reactive site loop (RSL) cleavage analysis showed that SQN-5 employed different reactive centers to neutralize the serine and cysteine proteinases. To our knowledge, this is the first serpin that serves as a dual inhibitor of both chymotrypsin-like serine and the papain-like cysteine proteinases by employing an RSL-dependent inhibitory mechanism. The ability of serpins to inhibit both serine and/or papain-like cysteine proteinases may not be a recent event in mammalian evolution. Phylogenetic studies suggested that the SCCA and SQN genes evolved from a common ancestor approximately 250-280 million years ago. When the fact that mammals and birds diverged approximately 310 million years ago is considered, an ancestral SCCA/SQN-like serpin with dual inhibitory activity may be present in many mammalian genomes.

Amino Acid Sequence↗
PubMed2004

TOR action in mammalian cells and in Caenorhabditis elegans.

The p70 S6 kinase (p70 S6K) was the first signaling element in mammalian cells shown to be inhibited by rapamycin. The activity of the p70 S6K in mammalian cell is upregulated by extracellular amino acids (especially leucine) and by signals from receptor tyrosine kinases (RTKs), primarily through activation of the type 1A PI-3 kinase. The amino acid-/rapamycin-sensitive input and the PI-3 kinase input are co-dominant but largely independent, in that deletion of the amino-terminal and carboxy-terminal noncatalytic sequences flanking the p70 S6K catalytic domain renders the kinase insensitive to inhibition by both rapamycin and by withdrawal of amino acids, whereas this p70 S6K mutant remains responsive to activation by RTKs and to inhibition by wortmannin. At a molecular level, this dual control of p70 S6K activity is attributable to phosphorylation of the two p70 S6K sites: The Ptd Ins 3,4,5P3-dependent kinasel (PDK1) phosphorylates p70 S6K at a Thr on the activation loop, whereas mTOR phosphorylates a Thr located in a hydrophobic motif carboxyterminal to the catalytic domain. Together these two phosphorylations engender a strong, positively cooperative activation of p70 S6K, so that each is indispensable for physiologic regulation. Like RTKs, the p70 S6K appears early in metazoan evolution and comes to represent an important site at which the more ancient, nutrient-responsive TOR pathway converges with the RTK/PI-3 kinase pathway in the control of cell growth. Dual regulation of p70 S6K is seen in Drosophila; however, this convergence is not yet evident in Caenorhabditis elegans, wherein nutrient activation of the insulin receptor (InsR) pathway negatively regulates dauer development and longevity, whereas the TOR pathway regulates overall mRNA translation through effectors distinct from p70 S6K, as in yeast. The C. elegans TOR and InsR pathways show none of the cross- or convergent regulation seen in mammalian cells. The nature of the elements that couple nutrient sufficiency to TOR activity remain to be discovered, and the mechanisms by which RTKs influence TOR activity in mammalian cells require further study. One pathway for RTK control involves the tuberous sclerosis complex, which is absent in C. elegans, but of major importance in Drosophila and higher metazoans.

Animals↗
PubMed2004

Prospective comparison of differences in bone mineral density adjacent to two biomechanically different types of cementless femoral stems.

We compared the differences in bone mineral density (BMD) adjacent to two biomechanically different cementless femoral stems (Spotorno and Evolution-K). Measurements were performed within the first week after surgery and 3, 6, 12, and 24 months postoperatively in a prospective study of 31 patients with 37 total hip arthroplasties. A modified Harris hip score and a visual analogue score for patient satisfaction was used to evaluate the clinical outcome. For both stems, dual X-ray absorptiometry measurements revealed a decrease in BMD in Gruen zone 7. Patients with a Spotorno stem also had a significant decrease in BMD in zones 1 and 2. In patients with an Evolution-K stem, there was a positive correlation between the clinical outcome and BMD in Gruen zones 1 and 4. Our data suggest that periprosthetic bone loss is equal to if not less pronounced adjacent to the Evolution-K stem as compared to the Spotorno stem.

Adult↗
PubMed1999

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.

Adult↗
PubMed2000

The water-water cycle as alternative photon and electron sinks.

The water-water cycle in chloroplasts is the photoreduction of dioxygen to water in photosystem I (PS I) by the electrons generated in photosystem II (PS II) from water. In the water-water cycle, the rate of photoreduction of dioxygen in PS I is several orders of magnitude lower than those of the disproportionation of superoxide catalysed by superoxide dismutase, the reduction of hydrogen peroxide to water catalysed by ascorbate peroxidase, and the reduction of the resulting oxidized forms of ascorbate by reduced ferredoxin or catalysed by either dehydroascorbate reductase or monodehydroascorbate reductase. The water-water cycle therefore effectively shortens the lifetimes of photoproduced superoxide and hydrogen peroxide to suppress the production of hydroxyl radicals, their interactions with the target molecules in chloroplasts, and resulting photoinhibition. When leaves are exposed to photon intensities of sunlight in excess of that required to support the fixation of CO2, the intersystem electron carriers are over-reduced, resulting in photoinhibition. Under such conditions, the water-water cycle not only scavenges active oxygens, but also safely dissipates excess photon energy and electrons, in addition to downregulation of PS II and photorespiration. The dual functions of the water-water cycle for protection from photoinhibition under photon excess stress are discussed, along with its functional evolution.

Chloroplasts↗
PubMedDate not supplied

Doctors having families: the effect of pregnancy and childbearing on relationships with patients.

Family physicians care for patients in all stages of the life-cycle, while at the same time proceeding themselves through the course of adult development. The purpose of this study was to examine, from the doctor's point of view, changes in the doctor-patient relationship resulting from the physician's pregnancy and child-bearing. Five faculty family physicians participated via individual interviews and group discussion. Two women without children, the clinical psychologist interviewer, and other faculty family physicians joined in the review of the interviews and the group discussion. Comprehensibility, reciprocity, mutuality, identification, credibility, availability for long-term relationships, nurturing, and support emerged as themes in the evolution of relationships with patients. The process of examining the effect of childbearing on our relationships with patients unexpectedly revealed how the dual expectation of career and motherhood causes colleagues without children to feel inadequate. On the other hand, the study itself had the positive effect of facilitating the resolution of long-standing tensions among group members. We conclude that becoming mothers, a significant life change, had a transforming effect on our clinical work with patients and that studying this effect as a group fostered growth in the relationships among the participants.

Adult↗
PubMed1986

Reliability and stability of the thymidine labeling index of breast carcinoma.

We have approached the question of the reliability of the thymidine labeling index (TLI) of breast carcinoma by comparing paired samples. Because the distribution of the TLI is approximately lognormal, comparisons were made after transformation to the natural logarithm. For 38 paired samples from the primary carcinoma (biopsy versus residual tumor in mastectomy specimen), r, 0.89, p less than 0.0001. For 68 primary carcinomas versus their axillary metastases, r, 0.90, p less than 0.0001. Substantial correlation was also observed between the TLIs of 18 primary breast carcinomas and their recurrent or metastatic lesions studied after relapse (r, 0.75, p less than 0.0003), and between 14 pairs of first and second primary carcinomas recovered from the same breast (r, 0.72, p less than 0.003). Good agreement was achieved among three observers in measuring the TLI from a set of breast carcinoma autoradiographs. We conclude that the TLI is sufficiently reliable for semiquantitative use as a means of separating breast carcinomas into groups with slow, moderate, and rapid rates of proliferation. The substantial similarities between the TLIs of breast carcinoma samples from different sites of the primary tumor, between primary tumor and axillary metastases, and between primary tumor and subsequent samples of relapsed tumor suggest that clonal evolution either is infrequent or does not usually affect the cell kinetics of the carcinoma. The similarity of the TLIs of synchronous dual primary carcinomas is an additional interesting finding.

Biopsy↗
PubMed2001

In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure.

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

Drug Resistance, Microbial↗