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Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53−/− mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53−/− mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

Amoebas infected with mimivirus were disrupted at sequential stages of virus production and were visualized by atomic force microscopy. The development of virus factories proceeded over 3 to 4 h postinfection and resulted from the coalescence of 0.5- to 2-μm vesicles, possibly bearing nucleic acid, derived from either the nuclear membrane or the closely associated rough endoplasmic reticulum. Virus factories actively producing virus capsids on their surfaces were imaged, and this allowed the morphogenesis of the capsids to be delineated. The first feature to appear on a virus factory surface when a new capsid is born is the center of a stargate, which is a pentameric protein oligomer. As the arms of the stargate grow from the pentamer, a rough disk the diameter of a capsid thickens around it. This marks the initial emergence of a protein-coated membrane vesicle. The capsid self-assembles on the vesicle. Hillocks capped by different pentameric proteins spontaneously appear on the emerging vesicle at positions that are ultimately occupied by 5-fold icosahedral vertices. A lattice of coat protein nucleates at each of the 5-fold vertices, but not at the stargate, and then spreads outward from the vertices over the surface, merging seamlessly to complete the icosahedral capsid. Filling with DNA and associated proteins occurs by the transfer of nucleic acid from the interior of the virus factory into the nearly completed capsids. The portal, through which the DNA enters, is sealed by a plug of protein having a diameter of about 40 nm. A layer of integument protein that anchors the surface fibers is acquired by the passage of capsids through a membrane enriched in the protein. The coating of surface fibers is similarly acquired when the integument protein-coated capsids pass through a second membrane that has a forest of surface fibers embedded on one side.

A common observation by protein chemists has been the appearance, for many proteins in aqueous solutions, of oil like droplets, or in more extreme cases the formation of a second oil like phase. These may accompany the formation of precipitate in “salting out” or “salting in’ procedures, but more commonly appear in place of any precipitate. Such phase separations also occur, with even greater frequency, in the presence of polymeric precipitants such as polyethyleneglycol (PEG). In general the appearance of a second liquid phase has been taken as indicative of protein aggregation, though an aggregate state distinctly different from that characteristic of amorphous precipitate. While the latter is thought to be composed of linear and branched assemblies, polymers of a sort, the oil phase suggests a more compact, three-dimensional, but fluid state. An important property of an alternate, fluid phase is that it can mediate transitions between other states, for example, between protein molecules free in solution and protein molecules immobilized in amorphous precipitate or crystals. The “liquid protein” phase can be readily observed in many crystallization experiments either prior to the appearance of visible crystals, or directly participating in the crystal growth process. In some cases the relationship between the liquid phase and developing crystals is intimate. Crystals grow directly from the liquid phase, or appear only after the visible formation of the liquid phase. We describe here our experience with a class of macromolecules, immunoglobulins, and particularly IDEC-151, an IgG specific for CD4 on human lymphocytes. This protein has been crystallized from a Jeffamine-LiSO 4 mother liquor and, its crystallization illustrates many of the features associated with the liquid protein, or protein rich phase.

Atomic force microscopy (AFM) has been used to image a variety of virus particles in vitro and could, conceivably, be used as a useful diagnostic for their presence, their structural characterization and even their identification. Virus particles can be imaged by AFM in air, under alcohol or in physiological medium, and accurate measurements of their dimensions obtained. In addition, the appearance and organization of capsomere structures on their surfaces are frequently visible. A number of viruses and virus crystals have been imaged successfully using AFM and improvements in AFM technology and sample handling will undoubtedly increase even more its power, resolution and scope.

The structure of canavalin, the vicilin-class storage protein from jack bean, was refined to 1.7 A resolution in a highly twinned rhombohedral crystal of space group R3 and unit-cell parameters a = b = c = 83.0 A, alpha = beta = gamma = 111.1 degrees. The resulting R and R(free) were 0.176 and 0.245, respectively. The orthorhombic crystal structure (space group C222(1), unit-cell parameters a = 136.5, b = 150.3, c = 133.4 A) was also refined with threefold non-crystallographic symmetry restraints. R and R(free) were 0.181 and 0.226, respectively, for 2.6 A resolution data. No significant difference in the protein structure was seen between these two crystal forms, nor between these two and the hexagonal and cubic crystal forms reported elsewhere [Ko et al. (1993), Acta Cryst. D49, 478-489; Ko et al. (1993), Plant Physiol. 101, 729-744]. A phosphate ion was identified in the lumen of the C-terminal beta-barrel. Lattice interactions showed that the trimeric molecule could be well accommodated in both 'top-up' and 'bottom-up' orientations in a rhombohedral unit cell of the R3 crystal and explained the presence of a high twin fraction. The large inter-trimer stacking interface of the C222(1) crystal may account for its relative stability. Atomic force microscopy (AFM) investigations of the growth of three crystal forms of canavalin indicate the rhombohedral form to be unique. Unlike the other two crystal forms, it contains at least an order of magnitude more screw dislocations and stacking faults than any other macromolecular crystal yet studied, and it alone grows principally by generation of steps from the screw dislocations. The unusually high occurrence of the screw dislocations and stacking faults is attributed to mechanical stress produced by the alternate molecular orientations in the rhombohedral crystals and their organization into discrete domains or blocks. At boundaries of alternate domains, lattice strain is relieved by the formation of the screw dislocations.

Satellite tobacco mosaic virus (STMV) was probed using a variety of proteases. Consequences of the degradation were analyzed using gel electrophoresis, quasi-elastic light scattering (QELS), and atomic force microscopy (AFM). Proteolysis rates of 30 minutes for complete degradation of the protein capsid, up to many hours, were investigated. With each protease, degradation of virions 17 nm in diameter was shown by QELS to result in particles of 10 nm diameter, which is that of the RNA core observed in the virion by x-ray diffraction analysis. This was verified by direct visualization with atomic force microscopy. Using QELS, it was further shown that freshly prepared RNA cores remain as individual, stable, 10-nm condensed particles for 12 to 24 h. Clusters of particles then formed, followed by very large aggregates of 500 to 1000 nm diameter. AFM showed that the aggregates were composed of groups of the condensed RNA cores and were not due to unfolding of the nucleic acid. No unfolding of the core particles into extended conformation was seen by AFM until the samples were heated well beyond 90 degrees C. Mass spectrometry of RNA core particles revealed the presence of a major polypeptide whose amino acid sequence corresponded to residues 2 through 25 of the coat protein. Amino acids 13 through 25 were previously observed to be in direct contact with the RNA and are presumably protected from protease digestion. Low resolution difference Fourier analyses indicated the courses of the remainders of the amino terminal strands (amino acids 2-12) in intact virions. Any individual strand appears to have several choices of path, which accounts for the observed disorder at high resolution. These positively charged strands, serving as virtual polyamines, engage the helical segments of RNA. The intimate association of amino acid residues 2 through 25 with RNA likely contributes to the stability of the condensed conformation of the nucleic acid cores.

Uniqueness in the linearised water-wave problem is considered for a fluid layer of constant depth containing two, three or four vertical barriers. The barriers are parallel, of infinite length in a horizontal direction, and may be surface-piercing and/or bottom mounted and may have gaps. The case of oblique wave incidence is included in the theory. A solution for a particular geometry is unique if there are no trapped modes, that is no free oscillations of finite energy. Thus, uniqueness is established by showing that an appropriate homogeneous problem has only the trivial solution. Under the assumption that at least one barrier does not occupy the entire fluid depth, the following results have been proven: for any configuration of two barriers the homogeneous problem has only the trivial solution for any frequency within the continuous spectrum; for an arbitrary configuration of three barriers the homogeneous problem has only the trivial solution for certain ranges of frequency within the continuous spectrum; for three-barrier configurations symmetric about a vertical line, it is shown that there are no correspondingly symmetric trapped modes for any frequency within the continuous spectrum; for four-barrier configurations symmetric about a vertical line, the homogeneous problem has only the trivial solution for certain ranges of frequency within the continuous spectrum. The symmetric four-barrier problem is investigated numerically and strong evidence is presented for the existence of trapped modes in both finite and infinite depth. The trapped mode frequencies are found for particular geometries that are in agreement with the uniqueness results listed above.

The goal of the study was to obtain a panel of monoclonal antibodies (MAb) against antigens of freshwater polyps of the genus Hydra. Hybrid mice F1(Balb/c × SJL/J) were immunized with cell membrane fraction of H. vulgaris and three months later their splenocytes were fused with cultured mouse myeloma cells 653A. Testing of culture fluids in ELISA with immobilized H. vulgaris cells, 82 hybridomas producing MAb were revealed. Study of MAb specificity in ELISA with H. vulgaris and H. oligactis cells indicated that 22% of them recognized only H. vulgaris antigens. About 50% of MAb recognized equally antigens of the both species. The rest of MAb reacted with H. vulgaris and H. oligactis antigens to different degree. Eight hybridomas producing MAb of all three above groups were adapted for growth as ascitic tumors. The distribution of antigens binding these MAb was studied in indirect immunofluorescence on fixed polyps, living or fixed cells, and on paraffin- embedded sections. Among the best studied MAb, of the greatest interest were the following reagents. One of them (1A10) revealed an antigen on surface membranes of ectodermal epithelial cells of H. vulgaris. The second one (1G10) was specific of the antigen located in mesoglea and basal cytoplasmic areas of ectodermal and entodermal epithelial cells of the both hydra species. The MAb 4G3 interacted with cytoplasmic antigen of ectodermal epithelia-muscular cells of the both hydra species. MAb 4H1 revealed nematocytes in H. vulgaris and H. oligactis. The data obtained indicate that in two species of hydra the epitopes binding the same MAb might be located in cells of different types.

(1 − x)PbFe1/2Nb1/2O3−x PbTiO3 (PFN-xPT) ferroelectric ceramics with low dielectric loss and pronounced anomalies of dielectric and pyroelectric properties near the ferroelectric-ferroelectric phase transition was obtained by doping with lithium. The temperature dependence of the position of the morphotropic boundary between the rhombohedral (monoclinic) and tetragonal phases in the x-T phase diagram of the PFN-xPT system was determined for the first time.

A chimeric human-simian IgG, antigen specific for CD4, when exposed to 0.5 M SO(=)(4) containing 0.4% polyethylene glycol or Jeffamine, self-assembles into discreet, roughly spherical particles 23 nm in diameter. Increasing SO(=)(4) to 1.55 M induces the IgG particles to crystallize in either a hexagonal or a monoclinic form. From X-ray diffraction, the former crystal is of space group P622, with one IgG particle in the unit cell; thus the particle itself must have 622 point group symmetry. Both crystal forms have been imaged using atomic force microscopy. Detailed features of the duodecamer were evident, including the symmetry and a large solvent channel along the sixfold axis. The particles in some ways resemble the hexameric IgG aggregates believed to activate compliment upon antigen binding and, therefore, may have physiological relevance. Investigation of seven other IgGs of diverse origins and subclasses indicates that many, if not most, IgGs form similar particles. To our knowledge, this is the first observation of the assembly of IgG into high symmetry aggregates in the absence of antigen or their crystallization.

Compounds in the double oxide systems of Nd 2 O 3 –BeO, Nd 2 O 3 –ZrO 2 , Nd 2 O 3 –ThO 2 , Nd 2 O 3 –Al 2 O 3 , Nd 2 O 3 –Cr 2 O 3 Nd 2 O 3 –Nb 2 O 5 have been synthesized by mixing the starting components nearly at the molecular level. Among the physical and chemical properties of these double oxides that have been determined are the melting points, the phase diagrams. The mechanism of syntheses of neodymium monoaluminate, chromite, and niobite have been elucidated. Based upon the results of this study, the technique of compound synthesis from molecular mixtures, followed by calcining at about 900°C, is recommended.

The reduction of shallow-water platform seas favorable for dolomite formation was one of the factors responsible for the decrease and shift of this process to the coastal zones. The carbonate accumulation was influenced by several factors, such as climatic, tectonic (subsidence rates and lithospheric plate position, which determined the shelf occurrence in favorable climatic zones), and global sealevel fluctuations, which controlled the shelf bathymetry and dimensions. The interrelation of these factors, as well as their influence on carbonate accumulation is very intricate and ambiguous. Therefore, none of them can be discriminated as preponderant. Differences in the Paleozoic and Mesozoic-Cenozoic carbonate accumulation and dolomite formation are outlined according to climatic environments, relationship with sealevel fluctuations, atmosphere composition, and other features.

Marine and oceanic carbonate accumulation during the Vendian-Cambrian was mostly controlled by the life activity of organisms, which either constructed skeletons and directly transferred carbonates into sediments or created geochemical environments favorable for the precipitation of the carbonate substance. During the first third of the Paleozoic, the chemogenic and biochemogenic mechanisms of limestone formation were replaced by the biogenic one. In the dolomite formation, to the contrary, the chemogenic mechanism progressively replaced the biochemogenic mechanism and its pseudobiogenic modification. The carbonate accumulation occurred in the cyclic mode and its intensity increased with time to reach its peak in the Late Cretaceous. The main paleogeographic domains of carbonate accumulation also experienced changes. They were mainly represented by spacious shelf seas in the Paleozoic; by intraoceanic shoals, reefs and pelagic realm in the Mesozoic; and by the pelagic realm and, to a lesser extent, reefs in the main Cenozoic.

International audience; The worldwide computing grid is essential to the LHC experiments in analysing the data collected by the detectors. Within LHCb, the computing model aims to simulate data at Tier-2 grid sites as well as non-grid resources. The reconstruction, stripping and analysis of the produced LHCb data will primarily place at the Tier-1 centres. The computing data challenge DC06 started in May 2006 with the primary aims being to exercise the LHCb computing model and to produce events which will be used for analyses in the forthcoming LHCb physics book. This paper gives an overview of the LHCb computing model and addresses the challenges and experiences during DC06. The management of the production of Monte Carlo data on the LCG was done using the DIRAC workload management system which in turn uses the WLCG infrastructure and middleware. We shall report on the amount of data simulated during DC06, including the performance of the sites used. The paper will also summarise the experience gained during DC06, in particular the distribution of data to the Tier-1 sites and the access to this data.

Using in situ atomic force microscopy (AFM) we have recorded the incorporation, on the nanometer scale, of molecules into growth steps of macromolecular crystals grown from solution. From these investigations we were able to deduce the fine structure of the growth step edges and the surface layer of the {101} faces of tetragonal thaumatin crystals. Although the height of the growth step corresponds to unit cells of eight molecules, step advancement occurs by ordered addition of individual protein molecules rather than molecular clusters. Advancement of growth steps in specific directions, which is anisotropic, occurs by formation of one-dimensional nuclei of varying sizes which generate subkinks on the step edges. Incorporation of molecules into kinks occurs through the same kind of nucleation process. The crystal surface as a whole is created from molecular chains parallel with the surface. Models for the packing of protein molecules comprising the surface layer, the structure of the step edges, and the structure of two-dimensional nuclei were developed which are consistent with the AFM images.

The uniqueness theorem of Simon & Ursell (1984), concerning the linearized two-dimensional water-wave problem in a fluid of infinite depth, is extended in two directions. First, we consider a two-dimensional geometry involving two submerged symmetric bodies placed sufficiently far apart that they are not confined in the vertical right angle having its vertex on the free surface as the theorem of Simon & Ursell requires. A condition is obtained guaranteeing the uniqueness outside a finite number of bounded frequency intervals. Secondly, the method of Simon & Ursell is generalized to prove uniqueness in the axisymmetric problem for bodies violating John's condition provided the free surface is a connected plane region.

The conception on which the affirmative philosophy of G.G. Shpet rests can be called hermeneutic phenomenology. The choice of this term demands explanation. Shpet's basic hermeneutic work, Hermeneutics and Its Problems [Germenevtika i ee problemy], was completed in 1918. At the time hermeneutics was understood usually as the art of grasping the meaning of a text. It is worth noting that this art (skill or technique) was quite specific. It consisted mostly of a set of psychological techniques for "penetrating" into the internal world of the text's author. The techniques were empathy, sympathy, immersion in a historico-cultural world, and imaginative penetration into the author's creative "workshop." Understood in this way, hermeneutics was a psychologically loaded research method. And if it is treated only in that way, the recently coined term "hermeneutic phenomenology" is in respect to content internally contradictory. As I see it, Shpet fully realized what conclusions could follow from this. Nevertheles...

The temperature dependences of the pyroelectric and dielectric properties of ferroelectric ceramics of the PbZr1 − x Ti x O3 binary system with x = 0.06, 0.07, 0.08, 0.1, 0.15, 0.2, 0.25, 0.3, and 0.35 have been obtained synchronously for each sample in the range of the structural phase transition between the states with the symmetry space groups R3c ↔ R3m. It is established that the temperatures of this phase transition for unpolarized and polarized samples coincide in the range 0.06 ≤ x ≤ 0.15. In this case, the x−T phase diagram, constructed on the basis of the pyroelectric and dielectric data, is in excellent agreement with the X-ray diffraction data on single crystals in this concentration range. The effect of dc electric fields from 5 × 105 V m−1 did not lead to any temperature shifts of the R3c ↔ R3m phase transition for the compositions with 0.06 ≤ x ≤ 0.25.

Atomic force microscopy (AFM) investigations have revealed that macromolecular crystals, during their growth, incorporate an extensive array of impurities. These vary from individual molecules to large particles, and microcrystals in the micron size range. AFM, along with X-ray topology, has further shown that the density of defects and faults in most macromolecular crystals is very high in comparison with conventional crystals. The high defect density is a consequence of the incorporation of impurities, misoriented nutrient molecules, and aggregates of molecules. High defect and impurity density, contributes to a deterioration of both the mechanical and the diffraction properties of crystals. In microgravity, access by impurities and aggregates to growing crystal surfaces is restricted due to altered fluid transport properties. We designed, and have now constructed an instrument, the observable protein crystal growth apparatus (OPCGA) that employs a fused optics, phase shift, Mach–Zehnder interferometer to analyze the fluid environment around growing crystals. Using this device, which will ultimately be employed on the international space station, we have, in thin cells on earth, succeeded in directly visualizing concentration gradients around growing protein crystals. This provides the first direct evidence that quasi-stable depletion zones formed around growing crystals in space may explain the improved quality of macromolecular crystals grown in microgravity. Further application of the interferometric technique will allow us to quantitatively describe the shapes, extent, and magnitudes of the concentration gradients and to evaluate their degree of stability.

Predictive control algorithms require an accurate mathematical model of the process under control. This paper shows how the classical Least-Squares algorithm can be extended to achieve simultaneous estimation of the parameters for all linear models with orders from 1 to n together with their associated loss functions in the delta-domain via a Lagrange multiplier technique. The resulting estimation algorithm can then be used to obtain adaptive, continuous-time and delta domain Generalized Predictive Control algorithms.

Atomic force microscopy (AFM) has been used to visualize events arising from the formation of intervening metastable phases at the surfaces of macromolecular crystals growing from solution. Crystals investigated were of the proteins canavalin, thaumatin, lipase, xylanase, and catalase, crystals of transfer RNA, and crystals of satellite tobacco mosaic virus. The appearance of aggregates on crystal surfaces was observed. The aggregates we infer to originate from liquid-protein droplets. These were particularly evident in freshly mixed mother liquor solutions. Droplets, upon sedimentation, have two possible fates. In some cases they immediately restructured as crystalline, multilayer stacks whose development was guided by, and contiguous with the underlying lattice. These contributed to the ordered growth of the crystal by serving as sources of growth steps. In other cases, liquid-protein droplets formed distinct microcrystals, somehow discontinuous with the underlying lattice, and these were subsequently incorporated into the growing substrate crystal. Scarring experiments with the AFM tip indicated that, detached from the crystal, molecules do not dissolve in the fluid phase but form metastable liquid-protein droplets with a potential to rapidly crystallize on the crystal surface. The molecular structure of the growth steps for thaumatin and lipase protein crystals were deduced. There is no step roughness due to thermal fluctuations, and each protein molecule which incorporated into the step edge remained. Growth steps propagate by addition of individual molecules which form subkinks of different size on the step edge.

Surface morphologies of thaumatin, catalase, lysozyme and xylanase crystals were investigated using in situ atomic force microscopy. For thaumatin, lysozyme and xylanase crystals, growth steps having a height equal to the unit cell parameter were produced both by screw dislocations and two-dimensional nuclei. Growth of catalase crystals proceeded in alternating patterns exclusively by two-dimensional nucleation and the successive deposition of distinctive growth layers, each having a step height equal to half the unit cell parameter. The shapes of islands on successive layers were related by 2-fold rotation axes along the 〈0 0 1〉 direction. Experiments revealed that step bunching on crystalline surfaces occurred either due to two- or three-dimensional nucleation on the terraces of vicinal slopes or as a result of uneven step generation by complex dislocation sources. Growth kinetics for thaumatin and catalase crystals were investigated over wide supersaturation ranges. Strong directional kinetic anisotropy in the tangential step growth rates in different directions was seen. From the supersaturation dependencies of tangential step rates and the rates of two-dimensional nucleation, the kinetic coefficients of the steps and the surface free energy of the step edge were calculated. Adsorption of impurities which formed filaments on the surfaces of catalase and thaumatin crystals was recorded. Cessation of growth of xylanase and lysozyme crystals was also observed and appeared to be a consequence of the formation of dense impurity adsorption layers. Crystal growth resumed upon scarring of the impurity adsorption layer and clearing of the crystal surface with the AFM tip. Adsorption of three-dimensional clusters, which consequently developed into either properly aligned multilayer stacks or misaligned microcrystals was recorded. For catalase crystals, incorporation of misoriented microcrystals as large as 50×3×0.1 μm 3 produced elastic deformations in growth layers of ≈0.6%, but did not result in the defect formation. Etching experiments on catalase crystals revealed high defect densities.

Studies conducted by the OAO Kompressor on the development of the AGNKS BK-75 in a modular containerized-unit design calculated for the refueling of 75 vehicles per day were reported at international scientific-technical symosiums and conferences on compressor equipment in 1995 and 1996.

This paper proposes a multiple model predictive control scheme for the case where the scheduling variable is the output of the nonlinear plant. By means of model interpolation and successive predictions, the resulting nonlinear strategy makes use of all models available for calculating future error predictions. Consistently good performance indicated by a simulated example confirms the usefulness of the proposed method.

Atomic force microscopy (AFM) has been used to visualize events arising from the formation of intervening metastable phases at the surfaces of macromolecular crystals growing from solution. Crystals investigated were of the proteins canavalin, thaumatin, lipase, xylanase, and catalase, crystals of transfer RNA, and crystals of satellite tobacco mosaic virus. Two types of aggregates were observed. The first were small, linear and branched aggregates, perhaps fractile in structure. These were incorporated into growing crystals as impurities, and they produced defects of various kinds. The second aggregate form we infer to be liquid-protein droplets which were particularly evident in freshly mixed protein-precipitant solutions. Droplets, upon sedimentation, have two possible fates. In some cases they immediately restructured as crystalline multilayer stacks whose development was guided by and contiguous with the underlying lattice. These contributed to the ordered growth of the crystal by serving as sources of growth steps. In other cases, liquid-protein droplets formed distinct microcrystals, somehow discontinuous with the underlying lattice, and these were subsequently incorporated into the growing substrate crystal with the formation of defects. Scarring experiments with the AFM tip indicated that liquid-protein droplets with the potential to rapidly crystallize were a consequence of concentration instabilities near the crystal's surfaces. The AFM study suggests that phase separation and the appearance of aggregates having limited order is a common occurrence in supersaturated macromolecular solutions such as the protein-precipitant solutions used for crystallization.

The nucleation and growth of protein, nucleic acid and virus crystals from solution are functions of underlying kinetic and thermodynamic parameters that govern the process, and these are all supersaturation-dependent. While the mechanisms of macromolecular crystal growth are essentially the same as for conventional crystals, the underlying parameters are vastly different, in some cases orders of magnitude lower, and this produces very different crystallization processes. Numerous physical features of macromolecular crystals are of serious interest to X-ray diffractionists; the resolution limit and mosaicity, for example, reflect the degree of molecular and lattice order. The defect structure of crystals has an impact on their response to flash-cooling, and terminal crystal size is dependent on impurity absorption and incorporation. The variety and extent of these issues are further unique to crystals of biological macromolecules. All of these features are amenable to study using atomic force microscopy, which provides direct images at the nanoscale level. Some of those images are presented here. © 2014 International Union of Crystallography All rights reserved.

Surface morphology, growth and dissolution of crystals of the protein catalase were studied by in situ atomic force microscopy (AFM). Growth of the (001) face of catalase crystals proceeds in alternating patterns by two-dimensional nucleation and successive deposition of two distinctive growth layers, each having a step height equal to half the unit cell parameter. Shapes of two-dimensional nuclei exhibit strong asymmetry due to directional anisotropy in step rates. The shapes of islands on successive layers are related by two-fold rotation axes along the 〈001〉 direction. Lattice resolution AFM images of the molecular structure of sequential surface layers were recorded. Adsorption of large three-dimensional clusters of molecules was also observed to occur on the surfaces of catalase crystals. These clusters developed into either properly aligned multilayer stacks or misaligned microcrystals. Incorporation of misoriented microcrystals as large as 50 × 3 × 0.1 μ m3 proceeded without formation of defects. Upon incorporation of microcrystals and subsequent deposition of new layers on the surface of a growing crystal, impressions with depths of up to 0.4 of the growth layer thickness formed due to misfits between the lattices of the microcrystals and those of the growth layers. This produced elastic deformations in growth layers of ≈0.6%.

In this paper numerical evidence for the existence of eigenvalues in a particular two‐dimensional water wave problem is presented, together with computations of the eigenvalues themselves. The geometry considered is that of a pair of identical inclined surface‐piercing barriers arranged symmetrically about a vertical line in infinitely deep water. Only oscillations symmetric about this line are considered so that the geometry is equivalent to an inclined surface‐piercing barrier next to a vertical wall. The problem is formulated as a hypersingular integral equation which is then solved numerically by expanding the unknown function, corresponding to the jump in potential across the barrier, as a series of Chebyshev polynomials. We also prove that for a more general class of bodies consisting of a pair of surface‐piercing bodies placed symmetrically about a vertical line midway between them, there are ranges of the spectral parameter for which no eigenvalues exist. The numerically computed eigenvalues for the inclined barriers are consistent with these results.

The Siberian Craton covers an area of about 4.5 million sq. km in northern Russia, of which up to 3.5 million sq. km may be prospective for hydrocarbons. The craton was consolidated in the Early Proterozoic, and above the basement granitoids and gneisses is a variable thickness of sedimentary strata ranging in age from Riphean (Middle-Late Proterozoic) to Quaternary. Reservoir rocks are known to occur in the interval between the Middle Riphean and the Upper Cretaceous; those of Riphean age have produced oil commercially since 1973. Geochemical data indicate that the oil within the Riphean reservoir rocks was generated by source rocks of Riphean age. Riphean reservoir rocks include both carbonates and siliciclastics, but commercial volumes of hydrocarbons have only been discovered within the carbonates. Three petroleum-bearing “provinces” or megabasins are located on the Siberian Craton: Lena-Tunguska, Lena-Vilyuyand Yenisey-Anabar. The Yurubchen-Tokhom Zone in Lena-Tunguska Province is potentially the most important oil-producing area in the craton, and comprises a number of distinct fields. Reservoir rocks here consist principally of thick Riphean dolomites. Both the development of reservoir characteristics within these dolomites and the formation of stratigraphic traps are related to an episode of emergence and karstification at the end of the Riphean.

I found Shpet's article "A Work on Philosophy" [Rabota po filosofii], which we present to the reader's attention, in the Shpet archives stored in the Lenin State Library and passed it on to the editorial board of the journal Logos, where it was published by I. Chubarov. The small circulation of that journal makes it appropriate to republish this text, which is of major importance for an understanding of Shpet's philosophical position and provides a good clarification of the subsequent logic of development of his conception. Although the article is unfinished, there is no reason to lament this fact, since all of its basic ideas and their logical development were realized by Shpet in subsequent publications. A whole series of his works is devoted to grounding and affirming so-called positive philosophy, the basic features of which I would like to clarify.

Productive reefs in the former USSR are known from the Lower Cambrian to the Upper Jurassic. They contain more than 31% of the oil and about 29% of the gas resources of the FSU occurring in carbonate reservoirs. Giant and supergiant fields such as Karachaganak, Tengiz, Zhanazhol, Shurtan etc. are associated with reefs. Reservoir architecture and variation of reservoir properties depends upon the shape and origin of the reefs. Zones of improved reservoir properties are located in the central parts of dome-like reefs or in circumferential or ring-shaped zones in the atoll-like reefs. In asymmetric reef systems the best reservoir intervals are shifted towards the bioherm zone and forereef slope.

This article presents the results of a study of clinical features of the development and course of alcohol dependence in patients with posttraumatic stress disorder (PTSD) in comparison with alcohol-dependent patients without PTSD. The highly progressive course, continuous alcohol consumption, high alcohol tolerance, rapidly emerged altered forms of alcohol intoxication, alcohol amnesias, alcohol withdrawal with the prevalence of psychopathological component, and more pronounced social and somatic consequences of alcohol abuse were characteristic of the PTSD group. At the same time, the alcohol-dependent patients with PTSD had the best outcome to the end of 12-month treatment with intramuscular injections of vivitrol.

This review of literature describes a role of chronic stress in the development of substance dependence including alcohol dependence. It is focused on neurochemical mechanisms of this dependence and approaches to its treatment in people with mental adaptation disorders. An example of treatment with injectable extended-release naltrexone is presented.

In a search for new breast cancer (BC) predisposing genes, we performed a whole exome sequencing analysis using six patient samples of familial BC and identified a germline inactivating mutation c.183delG [p. Arg61fs] in an orphan G protein-coupled receptor GPRC5A. An extended case-control study revealed a tenfold enrichment for this mutation in BC patients carrying the 5382insC allele of BRCA1, the major founder mutation in the Russian population, compared to wild-type BRCA1 BC cases [6/117 (5.1%) vs. 8/1578 (0.5%), p = 0.0002]. In mammary tumors (n = 60), the mRNA expression of GPRC5A significantly correlated with that of BRCA1 (p = 0.00018). In addition, the amount of GPRC5A transcript was significantly lower in BC obtained from BRCA1 mutation carriers (n = 17) compared to noncarriers (n = 93) (p = 0.026). Accordingly, a siRNA-mediated knockdown of either BRCA1 or GPRC5A in the MDA-MB-231 human BC cell line reduced expression of GPRC5A or BRCA1, respectively. Knockdown of GPRC5A also attenuated radiation-induced BRCA1- and RAD51-containing nuclear DNA repair foci. Taken together, these data suggest that GPRC5A is a modifier of BC risk in BRCA1 mutation carriers and reveals a functional interaction of these genes.

During the Early Permian deep-water basins existed in the southeastern part of the Russian craton. North and west of the Cis-Ural foredeep and the Precaspian depression (micro-ocean) carbonate platforms were formed on a shallow-marine shelf during the Asselian, Sakmarian and Early Artinskian. Reefs developed on the margin of these platforms along the slopes of the Cis-Ural foredeep and the Precaspian depression. The reefs shifted platform ward in the eastern areas, due to the tectonic subsidence of the platform margin and at the same time, prograded basinward in the south. Movements of continental blocks from the south during the Late Artinskian and Kungurian caused the separation of the Early Permian basin of the Russian craton from the Palaeo-Tethys, followed by evaporite sedimentation in the restricted basins.

The chemical, mechanical and diffraction properties of crystals grown from solution, as well as their growth kinetics and morphological development, depend very much on the types and concentrations of impurities present in their mother liquor. The situation appears vastly more complicated in the case of macromolecular crystals because of the complex nature of the molecules and the biochemical milieu from which they are derived. An attempt is made here to catalog and characterize these various impurities. One class of impurities, large foreign particles (such as dust), microcrystals, misoriented three-dimensional nuclei, and large molecular clusters has been investigated in detail using atomic force microscopy. With this technique we have directly visualized the incorporation of such larger impurities and have delineated some of their more striking consequences. In particular we have found that in some cases such incorporation is accompanied by visible defect formation or dislocations. In other cases of small three-dimensional nuclei, coalescence proceeds in a smooth manner, with alignment and knitting together of the respective lattices. A calculation of the overall defect density in canavalin crystals shows the number of defects to be many orders of magnitude greater than found for most conventional crystals.

In situ atomic force microscopy was utilized in studies of the growth mechanisms of six protein and virus crystals. It was demonstrated that those macromolecules utilize all of the growth mechanisms found in the crystallization of conventional molecules. These include growth on screw dislocations and by two- and three-dimensional nucleation. In addition the mechanism of normal growth was observed as well. Estimates for the fundamental parameters (free energy of the step edge, α, and kinetic coefficient of steps, β) for the crystallization of some macromolecules were obtained and compared with those known for inorganic crystals grown from solution.

Disorder in macromolecular crystals arises from several sources. Among the most important are thermal motion and the inherent mobility of the molecules. These cause statistical misalignment about mean lattice points and structural heterogeneity of the molecules. Defects in the crystal lattice, however, could also significantly affect the resolution and quality of diffraction data collected from some crystals. There is a considerable diversity in the sources of defects found in crystals, such as impurity incorporation and fluctuations of growth conditions, and the defects occur in a variety of structural forms. We have usedin situatomic force microscopy to visualize examples of several of the different classes of defects that occur in protein and virus crystals, ranging from unoccupied lattice sites (vacancies) to linear defects to stacking faults. In addition, we have calculated the defect density in several different macromolecular crystals and found that it varied in the range of 104–106cm−2. Indeed, some preliminary evidence suggests that the ultimate resolution to which a crystal diffracts may be a composite function of its inherent statistical disorder and its defect structure, density, and distribu tion.

In situ laser Michelson interferometry was utilized to investigate the growth kinetics and surface morphology in canavalin, thaumatin, and turnip yellow mosaic virus (TYMV) crystallization. Interferometric patterns and kinetic measurements from growing macromolecular crystals as small as 20 μm were obtained. This study shows that for the crystallization of canavalin, dislocations are the sources of growth steps on the surfaces of growing crystals. Supersaturation dependencies of the normal growth rates, tangential growth step velocities, and the slopes of the dislocation hillocks were determined. The kinetic coefficient β was estimated for canavalin grown from two different precipitant systems to be 3.2 × 10 −4 and 5.3 × 10 −4 cm s −1 , respectively. The change in activities of dislocation sources under different growth conditions was analyzed.

The results of the calculated analysis of cooling down the magnetic system of the synchrotron-Nuclotron from 300 K to 4.5 K are presented. The principle of the calculations is described. The calculated results are compared with the experimental data on cooling down the superconducting magnetic system of the Nuclotron. Recommendations of choosing an optimum condition of cooling down are given.

In the course of time-lapse video and atomic force microscopy (AFM) investigations of macromolecular crystal growth, we frequently observed the sedimentation of microcrystals and three-dimensional nuclei onto the surfaces of much larger, growing protein or virus crystals. This was followed by the direct incorporation over time of the smaller crystals into the bulk of the larger crystals. In some cases, clear indications were present that upon absorption of the small crystal onto the surface of the larger, there was proper alignment of the respective lattices, and consolidation proceeded without observable defect formation, i.e., the two lattices knitted together without discontinuity. In the case of at least one virus crystal, cubic satellite tobacco mosaic virus (STMV), addition of three-dimensional nuclei and subsequent expansion provided the principal growth mechanism at high supersaturation. This process has not been reported for growth from solution of conventional crystals. In numerous other instances, the lattices of the small and larger crystals were obviously misaligned, and incorporation occurred with the formation of some defect. This phenomenon of small crystals physically embedded in larger crystals could only degrade the overall diffraction and materials properties of macromolecular crystals.