On the distribution of the epoch of the first contact of immunocompetent cell with antigen

A hypothesis on the dynamics of the immune reaction at a cellular level is considered, as was presented by Šterzl (1967). According to this hypothesis, the onset of the immune response depends on the first contact of a so-called virgin immunocompetent cell with the antigen. In the present paper a conditional probability distribution of the epoch of this first contact is derived, assuming that such a contact occurs at all (probability of non-occurrence of the contact being, in the general case, positive); the density of this distribution (7) is then specified (8) for the case that decrease of the quantity of an active antigen follows an exponential curve, and moments of this distribution are calculated (12).     

Forms of the Word and the Mystery of the Objectified Nature of the Word

The time has come to proceed from forms of givenness of the word to forms of the word as such. They can, if you like, be called external and inner structures. Humboldt, however, preferred to speak of the external and inner forms of the language. Shpet adopted precisely this distinction. Why did this problem interest Shpet? Already in [Appearance and sense], he had set the task of returning to the source of pretheoretical, living science. Shpet wrote that the outer cover of words and logical expressions obscure the objectified meaning and that it was necessary to remove another cover from the objectified sign so as to grasp a certain genuine intimacy, and in it the fullness of being (Shpet, 1914. Pp. 5-6). We shall keep in mind this major undertaking posed by this scientist. The existence of the inner form of words should not come as a surprise. That same year (1914) Ortega y Gasset wrote that material objects have a third dimension. However, we cannot see or touch it: "For just as depth needs a surface beneath which to be concealed, the surface, or outer cover, in order to be so, needs something over which to spread, covering it" (Ortega y Gasset, 2000. Pp. 62-63).     

On the paradoxical determinations of the lacuno-canalicular permeability of bone

The lacuno-canalicular permeability has been shown to play a key role in the behavior of bone tissue. The aim of this study is, by giving an overview of the determinations of this parameter, to question the paradoxical values provided by theoretical predictions and recent experimental measurements. We propose therefore a Kozeny-like law obtained by a numerical method which relates the permeability to the textural parameters of cortical bone microstructure. Moreover, we suggest possible explanations for this paradox considering the empirical difficulties and possible multiphysical effects.     

Hastening death and the boundaries of the self

When applying moral principles to concrete cases, we assume a background shared understanding of the boundaries of the persons to whom the principles apply. In most contexts, this assumption is unproblematic. However, in end-of-life contexts, when patients are receiving 'artificial' life-support, judgments about where a person's self begins and ends can become controversial. To illustrate this possibility, this paper presents a case in which a decision must be made whether to deactivate a patient's pacemaker as a means to hasten his death. After discussing some common moral principles that are often applied to resolve ethical problems at the end of life and after explaining why they are of no help here, the paper argues that the correct analysis of this case, and of cases of this sort, turns on considerations that relate to the constitution of the self. These considerations, the paper further argues, sometimes resist resolution. The constitution of the self is fixed in large measure by our concepts and social conventions, and these do not always provide determinate grounds for delimiting the boundaries of the self.     

Relationship between lordosis and the position of the centre of reaction of the spinal disc

Whenever we stand upright in apparent static equilibrium, we are, in fact, continuously making minor adjustments in order to maintain our balance. For each intervertebral joint, a point must exist at which all moments applied to the joint are continually and dynamically balanced. This point, known as the centre of reaction, is a mathematical invention necessary to perform analyses of spinal motion, but which need not be associated with any real anatomical structure.As the spine flexes and extends, this centre is expected to move; where it moves and the rationale for its motion is worthy of enquiry. In this paper, we propose that the centre of reaction remains confined to the nucleus of the disc, but only if one simple but crucial assumption is made; that the motion of the spine and control of its musculature maintain a minimum and equal stress at each intervertebral joint. This is a simple hypothesis which imposes a very specific relationship between lordosis and the centre of reaction. We investigate this relationship and its consequences on the teaching of lifting.The impossibility of designing experiments adequately to verify this hypothesis prevents in vivo verification, and, therefore, the model's verification must be made through the inferred consequences. For example, the capability of correctly predicting physiological responses of the musculoskeletal system is an indication of the validity of a model; however, this is not universally accepted. In this particular case, additional experimental data are available in the form of the locus of the centre of rotation of a vertebra vis-à-vis its lower neighbour as the spine flexes and extends.It is instructive to compare the predicted locus of the centre of reaction to experimentally determined locus of the centre of rotation; more than just coincidental similarities are found.     

To the ways of the most reasonable implementation of digital radiography into the practical public health of the Russian Federation

The main idea of the authors' paper is to propose the most reasonable way of actively introducing the digital principle into the traditional roentgenological section of radiation diagnosis. For this, a luminophore digital radiography system has been chosen. The authors of the paper give a full-scale assessment and appropriate recommendations for its use. The paper essentially discusses the entire complex of matters that permit assessment whether its sound use is possible in regional and municipal health care systems. This is both a section devoted to a dose load, by making a comparative assessment of luminophore radiography and "the green system" and a study of different clinical diseases (456 cases). In their study, the authors have applied an original principle in the formation of an image obtained and some other approaches in order to make a comprehensive assessment of this method. In the authors' opinion, luminophore radiography has a variety of advantages. Firstly, this technique can be simultaneously applied to several nondigital apparatuses, including those available in the ward and it shows a rather diagnostic effectiveness and economic profitability, yields a qualitative image of varying density tissues upon single exposure, and has some other capacities of the CR system as a digital technique. All this things considered, the authors consider that luminophore radiography may be one of the main ways of introducing a digital technique into the conventional roentgenological section of radiation diagnosis at the level of regional and municipal heath care systems.     

Probing the role of the ATP-operated clamp in the strand-passage reaction of DNA gyrase.

The high-resolution structure of the 43 kDa N-terminal fragment of the DNA gyrase B protein shows a large cavity within the protein dimer. The approximate size of this cavity is 20 A, suggesting it could accommodate a DNA helix. Computer-modelling studies of this cavity suggest that it contains a constriction, reducing the width to approximately 13 A, principally caused by the side chain of Arg286. We have used site-directed mutagenesis to alter this residue to Gln. Gyrase bearing this mutation shows virtually no supercoiling activity and near-normal relaxation and DNA cleavage activities. The mutated protein has ATPase activity which cannot be stimulated by DNA. These data support the proposed role of the 43 kDa domain as an ATP-operated clamp which binds DNA during the supercoiling cycle. The lack of DNA-dependent ATPase of the mutant may indicate that binding of DNA within the clamp is a prerequisite for stimulation of the ATPase activity.     

Electron microscope study of the effect of temperature on the length of the tail of the myosin molecule

The effect of temperature on the length of the tail of the myosin molecule has been studied by negative staining of molecules immobilized on carbon substrates at different temperatures. In buffers containing chloride as the principal anion, tail length was approximately constant up to 25 degrees C. Above this temperature, it shortened linearly with increasing temperature up to 42 degrees C, the highest temperature studied in this solvent. The amount of shortening per degree C was about 1.2 nm. A similar amount of shortening per degree C was seen in acetate-containing buffers up to 50 degrees C, but in this case it did not begin until the temperature exceeded about 40 degrees C. A large fraction of the observed shortening was localized in a region that lies roughly between the two positions in the tail where proteolysis results in production of short or long subfragment-2. Frequently, the tail had a different appearance in this region from elsewhere and could sometimes be seen to split into two strands that were separate but coiled around one another.     

Robustness of the approximate likelihood of the protracted speciation model

The protracted speciation model presents a realistic and parsimonious explanation for the observed slowdown in lineage accumulation through time, by accounting for the fact that speciation takes time. A method to compute the likelihood for this model given a phylogeny is available and allows estimation of its parameters (rate of initiation of speciation, rate of completion of speciation and extinction rate) and statistical comparison of this model to other proposed models of diversification. However, this likelihood computation method makes an approximation of the protracted speciation model to be mathematically tractable: it sometimes counts fewer species than one would do from a biological perspective. This approximation may have large consequences for likelihood‐based inferences: it may render any conclusions based on this method completely irrelevant. Here, we study to what extent this approximation affects parameter estimations. We simulated phylogenies from which we reconstructed the tree of extant species according to the original, biologically meaningful protracted speciation model and according to the approximation. We then compared the resulting parameter estimates. We found that the differences were larger for high values of extinction rates and small values of speciation‐completion rates. Indeed, a long speciation‐completion time and a high extinction rate promote the appearance of cases to which the approximation applies. However, surprisingly, the deviation introduced is largely negligible over the parameter space explored, suggesting that this approximate likelihood can be applied reliably in practice to estimate biologically relevant parameters under the original protracted speciation model.     

Times of crisis in the evolution of the cephalopoda

The evolutionary history of the ectocochlian cephalopods is punctuated by a number of severe crises during each of which this class came very close to extinction. The crisis events follow each other at intervals of from seven to almost 300 million years and, with one exception, were not synchronous for Nautiloidea and Ammonoidea. Only at the end of the Triassic period did both groups simultaneously face the danger of extinction. Generally, the survivors of crisis situations have simple shell forms and are strikingly similar to each other. To trace the details of cephalopod evolution, the family on the taxonomic level and the stratigraphic stage on the chronological level do not provide scales fine enough to reconstruct the true course of this process. The causes of crises and “mass extinctions” are not yet understood. Most authors have approached this problem in a simplistic manner, searching for a single cause for any, or all, events of this kind. It seems that we do not even have begun to understand what the problems are.     

Effect of the anisotropic permeability in the frequency dependent properties of the superficial layer of articular cartilage

Abstract

Articular cartilage is a tissue of fundamental importance for the mechanics of joints, since it provides a smooth and lubricated surface for the proper transfer of loads. From a mechanical point of view, this tissue is an anisotropic poroviscoelastic material: its characteristics at the macroscopic level depend on the complex microscopic architecture. With the ability to probe the local microscopic features, dynamic nanoindentation test is a powerful tool to investigate cartilage mechanics. In this work we focus on a length scale where the time dependent behaviour is regulated by poroelasticity more than viscoelasticity and we aim to understand the effect of the anisotropic permeability on the mechanics of the superficial layer of the articular cartilage. In a previous work, a finite element model for the dynamic nanoindentation test has been presented. In this work, we improve the model by considering the presence of an anisotropic permeability tensor that depends on the collagen fibers distribution. Our sensitivity analysis highlights that the permeability decreases with increasing indentation, thus making the tissue stiffer than the case of isotropic permeability, when solicited at the same frequency. With this improved model, a revised identification of the mechanical and physical parameters for articular cartilage is provided. To this purpose the model was used to simulate experimental data from tests performed on bovine tissue, giving a better estimation of the anisotropy in the elastic properties. A relation between the identified macroscopic anisotropic permeability properties and the microscopic rearrangement of the fiber/matrix structure during indentation is also provided.     

Comparison of the predicted structure for the activated form of the P21 protein with the X-ray crystal structure

The predicted conformation and position of the central transforming region (residues 55–67) of the p21 protein are compared with the conformation and position of this segment in a recently determined X-ray crystal structure of residues 1–166 of this protein in the activated state bound to a nonhydrolyzable GTP derivative. We previously predicted that this segment of the protein would adopt a roughly extended conformation from Ile 55-Thr 58, a reverse turn at Ala 59-Gln 61, followed by an -helix from Glu 62-Met 67. We further predicted that this region of the activated protein occupies a position that is virtually identical to corresponding regions in the homologous purine nucleotide-binding proteins, bacterial elongation factor (EF-tu), and adenylate kinase (ADK). We find that there is a close correspondence between the conformation and position of our predicted structure and those found in the X-ray crystal structure. A mechanism for activation of the protein is proposed and is corroborated by X-ray crystallographic data.     

Isolation and structure of the replicon of the promiscuous plasmid pCU1

Evidence is presented to indicate that a PvuII fragment of approx. 2 kb isolated from the 39-kb IncN-group plasmid pCU-1 contains all plasmid-borne determinants for stable maintenance as an extrachromosomal element in Escherichia coli K-12. The fragment was sequenced. The features of this sequence include a group of 13 direct tandem repeats of 37 bp and a second group of two other direct repeats of 30 bp flanking a third partial member of this group. In addition, for a 19-bp sequence that overlaps a member of this second group, there are inverted repeats that straddle the members of the first group. There are three open reading frames within the fragment. We compare features of this sequence with that of other plasmid replicons and draw attention to similar and to dissimilar features.     

On the determination of the angular orientation of a vertebra

In this paper we consider the spatial orientation of vertebrae. We take the view that, in determining their rotation angles from X-rays, the procedure applied by Drerup yields the most reliable empirical results, viz. the three angles through which a vertebra rotates about its own symmetry axes in a specific sequence. With a view to the further use of this information to analyze deformations or the motion of a spine we recommend that the Drerup angles be converted into the well-known Eulerian angles. How this can be done is the subject of this report.     

Characterisation of the RNA interference response against the long-wavelength receptor of the honeybee

Targeted knock-down is the method of choice to advance the study of sensory and brain functions in the honeybee by using molecular techniques. Here we report the results of a first attempt to interfere with the function of a visual receptor, the long-wavelength-sensitive (L-) photoreceptor. RNA interference to inhibit this receptor led to a reduction of the respective mRNA and protein. The interference effect was limited in time and space, and its induction depended on the time of the day most probably because of natural daily variations in opsin levels. The inhibition did not effectively change the physiological properties of the retina. Possible constraints and implications of this method for the study of the bee's visual system are discussed. Overall this study underpins the usefulness and feasibility of RNA interference as manipulation tool in insect brain research.     

Folding and stability of the ligand-binding domain of the glucocorticoid receptor

A complex pathway involving many molecular chaperones has been proposed for the folding, assembly, and maintenance of a high-affinity ligand-binding form of steroid receptors in vivo, including the glucocorticoid receptor. To better understand this intricate folding and assembly process, we studied the folding of the ligand-binding domain of the glucocorticoid receptor in vitro. We found that this domain can be refolded into a compact, highly structured state in vitro in the absence of chaperones. However, the presence of zwitterionic detergent is required to maintain the domain in a soluble form. In this state, the protein is dimeric and has considerable helical structure as shown by far-UV circular dichroism. Further investigation of the properties of this in vitro refolded state show that it is stable and resistant to denaturation by heat or low concentrations of chemical denaturants. A detailed analysis of the unfolding equilibria using three different structural probes demonstrated that this state unfolds via a highly populated dimeric intermediate state. Together, these data clearly show that the ligand-binding domain of the glucocorticoid receptor does not require chaperones for folding per se. However, this in vitro refolded state binds the ligand dexamethasone only weakly (K(d) = 45 microM) compared to the in vivo assembled receptor (K(d) = 3.4 nM). We suggest that the role of Hsp90 and associated chaperones is to bind to, and stabilize, a specific conformational state of the receptor which binds ligand with high affinity.     

Prospects for the involvement of cancer stem cells in the pathogenesis of osteosarcoma

Osteosarcoma (OS) is one of the most common bone tumors in children and adolescents that cause a high rate of mortality in this age group and tends to be metastatic, in spite of chemotherapy and surgery. The main reason for this can be returned to a small group of malignant cells called cancer stem cells (CSCs). OS-CSCs play a key role in the resistance to treatment and relapse and metastasis through self-renewal and differentiation abilities. In this review, we intend to go through the different aspects of this malignant disease, including the cancer stem cell-phenotype, methods for isolating CSCs, signaling pathways, and molecular markers in this disease, and drugs showing resistance in treatment efforts of OS.     

On the computational architecture of the neocortex

This paper proposes that each area of the cortex carries on its calculations with the active participation of a nucleus in the thalamus with which it is reciprocally and topographically connected. Each cortical area is responsible for maintaining and updating the organism's knowledge of a specific aspect of the world, ranging from low level raw data to high level abstract representations, and involving interpreting stimuli and generating actions. In doing this, it will draw on multiple sources of expertise, learned from experience, creating multiple, often conflicting, hypotheses which are integrated by the action of the thalamic neurons and then sent back to the standard input layer of the cortex. Thus this nucleus plays the role of an 'active blackboard' on which the current best reconstruction of some aspect of the world is always displayed. Evidence for this theory is reviewed and experimental tests are proposed. A sequel to this paper will discuss the cortico-cortical loops and propose quite different computational roles for them.