Showing papers by "Weizmann Institute of Science published in 1991"
TL;DR: Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.
Abstract: The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.
2,489 citations
TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
2,448 citations
TL;DR: In this article, wild-type p53 protein has many properties consistent with its being the product of a tumour suppressor gene, which could be involved in promoting cell differentiation as well as in mediating growth arrest by growthinhibitory cytokines.
Abstract: Wild-type p53 protein has many properties consistent with its being the product of a tumour suppressor gene. Although the normal roles of tumour suppressor genes are still largely unknown, it seems that they could be involved in promoting cell differentiation as well as in mediating growth arrest by growth-inhibitory cytokines. Hence, the abrogation of wild-type p53 expression, which is a common feature of many tumours, could eliminate these activities. We have now tested this notion by restoring the expression of p53 in a murine myeloid leukaemic cell line that normally lacks p53. The use of a temperature-sensitive p53 mutant allowed us to analyse cells in which the introduced p53 had either wild-type or mutant properties. Although there seemed to be no effect on differentiation, the introduction of wild-type p53 resulted in rapid loss of cell viability in a way characteristic of apoptosis (programmed cell death). The effect of wild-type p53 was counteracted by interleukin-6. Thus products of tumour suppressor genes could be involved in restricting precursor cell populations by mediating apoptosis.
2,143 citations
TL;DR: This work reports remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input and suggests that learning involves experience-dependent changes at a level of the visual system where monocularity and the retinotopic organization of thevisual input are still retained and where different orientations are processed separately.
Abstract: In terms of functional anatomy, where does learning occur when, for a basic visual discrimination task, performance improves with practice (perceptual learning)? We report remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input. This learning is (i) local (in a retinotopic sense), (ii) orientation specific but asymmetric (it is specific for background but not for target-element orientation), and (iii) strongly monocular (there is little interocular transfer of learning). Our results suggest that learning involves experience-dependent changes at a level of the visual system where monocularity and the retinotopic organization of the visual input are still retained and where different orientations are processed separately. These results can be interpreted in terms of local plasticity induced by retinal input in early visual processing in human adults, presumably at the level of orientation-gradient sensitive cells in primary visual cortex.
1,055 citations
TL;DR: The theory of the immunological homunculus is presented here as a unifying principle to explain certain key features of immune behaviour: the Immunological dominance of microbial antigens that mimic self, the uniformity of autoimmune diseases and the prevalence of natural autoimmunity among the healthy.
495 citations
TL;DR: This work has applied the wedge model of DNA curvature to a large body of experimental data and found that the stacks AG/CT, CG/CG, GA/TC, and GC/GC, in addition to AA/TT, have large wedge values.
Abstract: The principal sequence feature responsible for intrinsic DNA curvature is generally assumed to be runs of adenines. However, according to the wedge model of DNA curvature, each dinucleotide step is associated with a characteristic deflection of the local helix axis. Thus, an important test of a more general view of sequence-dependent DNA curvature is whether sequence elements other than A-A cause the DNA axis to deflect. To address this question, we have applied the wedge model to a large body of experimental data. The axial path of DNA can be described at each step by three Eulerian angles: the helical twist, the deflection angle (wedge angle), and the direction of the deflection. Circularization and gel electrophoretic mobility data on 54 synthetic DNA fragments, both from other laboratories and from our own, were used to compare the theoretical predictions of the wedge model with experiment. By minimizing misfit between calculated and observed DNA curvature, we have found that the stacks AG/CT, CG/CG, GA/TC, and GC/GC, in addition to AA/TT, have large wedge values. We have also synthesized seven sequences without AA/TT elements but with these other wedges correctly phased to cause appreciable predicted curvature. All appear curved as demonstrated by anomalous gel mobilities. The full set of 16 roll and tilt wedge angles is estimated and, together with the known 10 helical twists, these allow prediction of the general sequence-dependent trajectory of the DNA axis.
456 citations
TL;DR: Immunofluorescent microscopic localization indicated that after heat treatment, the levels of the 25-kD IAP were markedly increased and the protein was apparently associated with cytoplasmic granules, confirming that its expression is regulated by heat shock.
Abstract: The 25-kD inhibitor of actin polymerization (25-kD IAP), isolated from turkey smooth muscle (Miron, T., M. Wilchek, and B. Geiger, 1988. Eur. J. Biochem. 178:543-553), is shown here to be a low molecular mass heat shock protein (HSP). Direct sequence analysis of the purified protein, as well as cloning and sequencing of the respective cDNA, disclosed a high degree of homology (67% identity, 80% similarity) to the human 27-kD HSP. Southern blot of chicken genomic DNA disclosed one band, suggesting the presence of a single gene, and Northern blot analysis revealed abundant transcript of approximately 1 kb in gizzard and heart tissues and lower amounts in total 18-d chick embryo RNA and in cultured fibroblasts. Exposure of the latter cells to 45 degrees C resulted in over 15-fold increase in the apparent level of the 25-kD IAP protein, confirming that its expression is regulated by heat shock. Immunofluorescent microscopic localization indicated that after heat treatment, the levels of the 25-kD IAP were markedly increased and the protein was apparently associated with cytoplasmic granules. Heat shock also had a transient, yet prominent, effect on the microfilament system in cultured fibroblasts: stress fibers disintegrated within 10-15 min after incubation at 45 degrees C, yet upon further incubation at the elevated temperature, conspicuous actin bundles were apparently reformed.
448 citations
TL;DR: A panel of monoclonal antibodies specific to the extracellular portion of the ERBB2 protein was generated and it was suggested that the antitumor antibodies affect both receptor function and host-tumor interactions.
Abstract: The ERBB2 (also called HER2, neu, and c-erbB-2) gene product, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. An antibody directed to the rat oncogenic receptor has been previously shown to have an antitumor effect in model systems. In an attempt to extend this observation to the protooncogenic human receptor and also to understand the underlying mechanism, we generated a panel of monoclonal antibodies specific to the extracellular portion of the ERBB2 protein. The effects of the antibodies on tumor growth were compared with their cellular and biochemical actions in vitro. Surprisingly, opposing in vivo effects were observed: although some antibodies almost completely inhibited the growth in athymic mice of transfected murine fibroblasts that overexpress Erbb-2, other antibodies either accelerated tumor growth or resulted in intermediate responses. When tested on cultured human breast carcinoma cells or ERBB2 transfectants, the tumor-stimulatory antibody was found to induce significant elevation of tyrosine phosphorylation of the ERBB2 protein. In contrast, only partial correlation was observed between the capacity to restrict tumor growth and the effects of the antibodies on receptor degradation and cellular proliferation in vitro. This suggests that the antitumor antibodies affect both receptor function and host-tumor interactions. Our results may help establish experimental criteria for the selection of specific antibodies for use either alone or in conjunction with other molecules as pharmacological antitumor agents.
446 citations
TL;DR: Kinetic studies indicate that the effect of wt p53 is rapid, rather than representing a secondary consequence of growth arrest, which support a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation.
Abstract: The wild-type (wt) p53 protein is the product of a tumor suppressor gene that is a frequent target for inactivation in many types of tumors. The nuclear localization of the protein, as well as additional features, suggest that it may be involved in the regulation of gene expression. To explore this possibility, the effects of overproduced wt p53 were investigated in a number of systems. Induction of growth arrest via the antiproliferative effect of wt p53 greatly impaired the ability of cells to exhibit an increase in c-fos mRNA upon serum stimulation. Experiments in which cells were cotransfected with p53 expression plasmids together with a reporter gene linked to various promoters revealed that wt p53 could effectively reduce transcription from a series of promoters derived from serum-inducible genes, but not from a major histocompatibility complex gene. The p53-mediated repression of c-fos gene expression occurred even in the presence of cycloheximide. Kinetic studies indicate that the effect of wt p53 is rapid, rather than representing a secondary consequence of growth arrest. These findings support a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation.
435 citations
TL;DR: T-cell vaccination and specific peptide therapy are feasible in spontaneous autoimmune diabetes and administration of the peptide itself to NOD mice can also down-regulate immunity to the 65-kDa heat shock protein and prevent the development of diabetes.
Abstract: Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing beta cells resident in the pancreatic islets. We recently discovered that the pathogenesis of diabetes in NOD strain mice was associated with T-cell reactivity to an antigen cross-reactive with a mycobacterial 65-kDa heat shock protein. To identify peptide epitopes critical to the insulin-dependent diabetes mellitus of NOD mice, we studied the specificities of helper T-cell clones capable of causing hyperglycemia and diabetes. We now report the identification of a functionally important peptide within the sequence of the human variant of the 65-kDa heat shock protein molecule. T-cell clones recognizing this peptide mediate insulitis and hyperglycemia. Alternatively, the T cells can be attenuated and used as therapeutic T-cell vaccines to abort the diabetogenic process. Moreover, administration of the peptide itself to NOD mice can also down-regulate immunity to the 65-kDa heat shock protein and prevent the development of diabetes. Thus, T-cell vaccination and specific peptide therapy are feasible in spontaneous autoimmune diabetes.
411 citations
03 Jun 1991
TL;DR: A specification language that refers to time only through age functions which measure the length of the most recent time interval in which a given formula has been continuously true is proposed.
Abstract: We propose a framework for the formal specification and verification of timed and hybrid systems. For timed systems we propose a specification language that refers to time only through age functions which measure the length of the most recent time interval in which a given formula has been continuously true.
TL;DR: A methodology is described for using ``tailor-made'' additives designed to interact stereospecifically with crystal surfaces during growth and dissolution that has led to the discovery of a new ``relay'' mechanism explaining the effect of solvent on crystal growth.
Abstract: Nucleation, growth, and dissolution of crystals have been studied by stereochemical approach involving molecular recognition at interfaces. A methodology is described for using ``tailor-made99 additives designed to interact stereospecifically with crystal surfaces during growth and dissolution. This procedure was instrumental in controlling crystal morphology and in revising the concept of the structure and symmetry of solid solutions. Consequently, it was applied to the transformation of centrosymmetric single crystals into solid solutions with polar arrangement displaying second-harmonic generation and to the performance of asymmetric synthesis of guest molecules inside centrosymmetric host crystals. The method has led to a discovery of a new ``relay99 mechanism explaining the effect of solvent on crystal growth. Finally, it allowed for the design of auxiliary molecules that act as promoters or inhibitors of crystal nucleation that can be used to resolve enantiomers and crystallize desired polymorphs.
TL;DR: The two receptors, in contrast to their almost identical ligand binding specificity, displayed distinct spatial specificities throughout development, suggesting that developmental localization may contribute to functional specificity.
Abstract: Developmental expression of two closely related fibroblast growth factor receptors, bek and flg, is described from early postimplantation until advanced organogenesis. Transcripts of bek and flg were first seen in the primitive ectoderm of egg-cylinder-stage embryos. Later, starting with somitogenesis, and then throughout embryogenesis, they were actively transcribed both in the mesoderm and neuroectoderm. Bek was expressed also in the surface ectoderm and in various epithelia, whereas flg expression was restricted mainly to the mesenchyme. In the limb bud bek transcripts displayed a gradient-like distribution and appeared earlier than flg. The two receptors, in contrast to their almost identical ligand binding specificity, displayed distinct spatial specificities throughout development, suggesting that developmental localization may contribute to functional specificity. The role of bek and flg in gastrulation and in epithelial-mesenchymal interactions of organogenesis will be discussed.
Book•
01 May 1991TL;DR: In this article, collective phenomena in neural networks are discussed, which is applied in subsequent chapters to the specific areas of dynamics and storage capacity of networks of formal neurons with symmetric or asymmetric couplings, learning algorithms, temporal association, structured data (software) and structural nets (hardware).
Abstract: This work aims to address the requirement for coverage of this multidisciplinary and rapidly changing field of research. It begins with an introduction to the central theme of the book, collective phenomena in neural networks, which is applied in subsequent chapters to the specific areas of dynamics and storage capacity of networks of formal neurons with symmetric or asymmetric couplings, learning algorithms, temporal association, structured data (software) and structural nets (hardware). This textbook on physics, computer science, artificial neuroscience, psychology, cognitive science and applied mathematics is intended for graduate students and researchers.
TL;DR: This paper studies the question of how an aimed arm movement is modified in response to a sudden change in target location occurring during the reaction or movement time and finds that the observations can be well accounted for by a different movement modification scheme.
Abstract: In this paper we study the question of how an aimed arm movement is modified in response to a sudden change in target location occurring during the reaction or movement time. Earlier monkey and human studies demonstrated that aimed arm movements can be elicited in quick succession, without appreciable delays in responding to the target displacement, beyond the normal reaction time. Nevertheless, it is not yet clear how this motor task is performed. A first guess is that when a new visual stimulus appears the old plan is aborted and a new one conceived. Upon analyzing human arm movements, however, we find that the observations can be well accounted for by a different movement modification scheme. It appears that a new plan is vectorially added to the original plan. Among the implications of this result is the possibility of parallel planning of elemental movements and further support for the idea that arm movements are internally represented in terms of hand motion through external space.
TL;DR: The design of a macroscope constructed with photography lenses is described and several applications are demonstrated, where the improved light collection efficiency and illumination throughput not only minimized bleaching effects, but, in concert with improved illumination throughput, significantly enhanced object visibility as well.
TL;DR: In this paper, the authors measured the forces that act between surfaces bearing polymer layers in a liquid medium as they slide past each other and found that the normal forces between them become increasingly repulsive at higher velocities.
Abstract: ADSORBED or grafted polymers are used to control phenomena such as colloidal stability, fluid flow and the tribological properties of surfaces. Forces between polymer-bearing surfaces have been studied comprehensively over the past decade1–10, but little is known about such forces in shear. These are intimately related to the dynamic as well as the equilibrium properties of the surface-attached chains. We have constructed a device that measures directly the forces that act between surfaces bearing polymer layers in a liquid medium as they slide past each other. For the case of mica sheets bearing end-grafted chains of polystyrene in toluene (a good solvent), we find that, as the surfaces move parallel to each other, there is a marked change in the normal forces between them. These become increasingly repulsive at higher velocities. The effect occurs only above certain critical shear rates, probably related to relaxation dynamics of the end-grafted chains themselves. Our findings have direct implications for the properties of polymeric lubricants, and for the rheological behaviour both of stabilized dispersions and of multi-phase polymeric systems.
TL;DR: A nomenclature system for the UDP glucuronosyltransferase superfamily is proposed, based on divergent evolution of the genes, which leads to the definition of two families and a total of three subfamilies and the suggestion that the human nomenClature system be used for species other than the mouse.
Abstract: A nomenclature system for the UDP glucuronosyltransferase superfamily is proposed, based on divergent evolution of the genes. A total of 26 distinct cDNAs in five mammalian species have been sequenced to date. Comparison of the deduced amino acid sequences leads to the definition of two families and a total of three subfamilies. For naming each gene, we propose that the root symbol UGT for human (Ugt for mouse), representing "UDP glucuronosyltransferase," be followed by an Arabic number denoting the family, a letter designating the subfamily, and an Arabic numeral representing the individual gene within the family or sub-family (hyphen before the Arabic number for mouse), e.g., human UGT2B1 and murine Ugt2b-1. Whereas the gene and cDNA should be italicized, the corresponding transcript, protein, and enzyme activity should not be written with lowercase letters or in italics, e.g., human or murine UGT2B1. Recent experimental evidence suggests that several exons of the UGT1 gene might be shared, ind...
03 Jun 1991
TL;DR: The scope of applicability for the abstract model of timed transition systems is explored and it is demonstrated that the model can represent a wide variety of phenomena that routinely occur in conjunction with the timed execution of concurrent processes.
Abstract: We incorporate time into an interleaving model of concurrency. In timed transition systems, the qualitative fairness requirements of traditional transition system are replaced (and superseded) by quantitative lower-bound and upperbound timing constraints on transitions. The purpose of this paper is to explore the scope of applicability for the abstract model of timed transition systems. We demonstrate that the model can represent a wide variety of phenomena that routinely occur in conjunction with the timed execution of concurrent processes. Our treatment covers both processes that are executed in parallel on separate processors and communicate either through shared variables or by message passing, and processes that time-share a limited number of processors under a given scheduling policy. Often it is this scheduling policy that determines if a system meets its real-time requirements. Thus we explicitly address such questions as time-outs, interrupts, static and dynamic priorities.
TL;DR: The three-dimensional structure of the lactose complex of the Erythrina corallodendron lectin (EcorL), a dimer of N-glycosylated subunits, was determined crystallographically and refined at 2.0 angstrom resolution.
Abstract: The three-dimensional structure of the lactose complex of the Erythrina corallodendron lectin (EcorL), a dimer of N-glycosylated subunits, was determined crystallographically and refined at 20 angstrom resolution to an R value of 019 The tertiary structure of the subunit is similar to that of other legume lectins, but interference by the bulky N-linked heptasaccharide, which is exceptionally well ordered in the crystal, forces the EcorL dimer into a drastically different quaternary structure Only the galactose moiety of the lactose ligand resides within the combining site The galactose moiety is oriented differently from ligands in the mannose-glucose specific legume lectins and is held by hydrophobic interactions with Ala88, Tyr106, Phe131, and Ala218 and by seven hydrogen bonds, four of which are to the conserved Asp89, Asn133, and NH of Gly107 The specificity of legume lectins toward the different C-4 epimers appears to be associated with extensive variations in the outline of the variable parts of the binding sites
01 Jan 1991
TL;DR: A simple statistic, a regression analysis predicting the function value from the bits, as a mean to measure the amount of nonlinearity in a representation, and an interesting perspective on GA-hardness are suggested.
Abstract: There is general consensus that the coding of a problem domain holds an important key to a successful application. However, there is disagreement as to what aspects of a representation and a problem domain make the application ‘hard’ for a genetic algorithm (GA). This paper suggests a simple statistic, a regression analysis predicting the function value from the bits, as a mean to measure the amount of nonlinearity in a representation, and an interesting perspective on GA-hardness. This statistics is termed epistasis variance for its analogy to the use of epistasis in genetics, and presents a perspective on GA-hardness different to those presented in recent works on deceptive problems. Two new findings result form the epistasis analysis. One, a step towards defining and understanding the role of epistasis in GAs, and in the search for understanding GA-hardness. Two, that three elements contribute to GA-hardness: the structure of the solution space, the representation of the solution space, and the sampling error as a result of finite and often small population sizes. These three elements are not necessarily linked, and furthermore, the effect of each of them on GA-hardness is not fixed.
TL;DR: This report provides the first direct demonstration of autonomous spine function through direct visualization and measurement of intracellular calcium concentrations in individual living spines, and demonstrates that experimentally evoked changes incium concentrations in the dendritic shaft are frequently not parallelled in the spine.
Abstract: THE dendritic spine is a basic structural unit of neuronal organization. It is assumed to be a primary locus of synaptic plasticity, and to undergo long-term morphological and functional changes1–6, at least some of which are regulated by intracellular calcium concentrations7–11. It is known that physiological stimuli can cause marked increases in intracellular calcium levels in hippocampal dendritic shafts12,13, but it is completely unknown to what extent such changes in the dendrites would also be seen by calcium-sensing structures within spines. Will calcium levels in all spines change in parallel with the dendrite or will there be a heterogeneous response? This study, through direct visualization and measurement of intracellular calcium concentrations in individual living spines, demonstrates that experimentally evoked changes in calcium concentrations in the dendritic shaft ([Ca2+]d) are frequently not parallelled in the spine ([Ca2+]s). This isolation is not caused by a physical diffusion barrier. This report provides, to our knowledge, the first direct demonstration of autonomous spine function.
24 Sep 1991
TL;DR: The proposed semantics maintains the synchrony hypothesis, by which the system is infinitely faster than its environment, and can always finish computing its response before the next stimulus arrives, but corrects some inconsistencies present in previous definitions, by requiring global consistency of the step.
Abstract: This paper presents a proposal for the definition of a step in the execution of a statechart. The proposed semantics maintains the synchrony hypothesis, by which the system is infinitely faster than its environment, and can always finish computing its response before the next stimulus arrives. However, it corrects some inconsistencies present in previous definitions, by requiring global consistency of the step.
TL;DR: In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties, which supports a role for olfactory UGT in terminating diverse odorant signals.
Abstract: The onset of olfactory transduction has been extensively studied, but considerably less is known about the molecular basis of olfactory signal termination. It has been suggested that the highly active cytochrome P450 monooxygenases of olfactory neuroepithelium are termination enzymes, a notion supported by the identification and molecular cloning of olfactory-specific cytochrome P450s (refs. 13-16). But as reactions catalysed by cytochrome P450 (refs 17, 18) often do not significantly alter volatility, lipophilicity or odour properties, cytochrome P450 may not be solely responsible for olfactory signal termination. In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties. We report here the molecular cloning and expression of an olfactory-specific UGT. The olfactory enzyme, but not the one in liver microsomes, shows preference for odorants over standard UGT substrates. Furthermore, glucuronic acid conjugation abolishes the ability of odorants to stimulate olfactory adenylyl cyclase. This, together with the known broad spectrum of drug-detoxification enzymes, supports a role for olfactory UGT in terminating diverse odorant signals.
TL;DR: A group of unusually acidic proteins and glycoproteins can interact specifically with some crystal faces but not others, induce oriented nucleation, or intercalate in a regular manner into the crystal lattice itself.
TL;DR: Algorithms for performing dense-matrix multiplication for n×n matrices representing the interaction of n particles or the discretization of integral transforms on n gridpoints are described.
TL;DR: Although the p53 gene is rarely rearranged, one p53 allele is completely deleted in patients with the i(17q) aberration as well as in some patients who do not show karyotypic changes.
Abstract: All patients with chronic myelogenous leukemia (CML) undergo clinical transition from chronic to acute phase. This transition is often associated with deletion of the short arm of chromosome 17 in the form of the i(17q) aberration. Since the p53 gene is a suppressor gene and is located on 17p13, we examined the possibility that it is inactivated during progression of CML. Therefore, we studied the structure and expression of p53 in the leukemic cells of a large number of CML patients in acute phase. We found that although the gene is rarely rearranged, one p53 allele is completely deleted in patients with the i(17q) aberration as well as in some patients who do not show karyotypic changes. In all of these patients the remaining allele is inactivated through loss of expression, rearrangement, or point mutation. Detailed analysis of some patients who carry both p53 alleles indicated neither loss of expression nor structural alterations. It appears that p53 loss of function is associated with progression of around 25% of CML patients.
TL;DR: The orbital susceptibility of a mesoscopic system, disorder averaged over the canonical ensemble, may be large and positive, even for systems which, on a larger scale, should exhibit Landau diamagnetism.
Abstract: Disorder-averaged thermodynamic quantities within the canonical ensemble are expressed in terms of fluctuations in the grand canonical ensemble, and are then evaluated for the diffusive regime. The particular example of persistent currents in Aharanov-Bohm geometries is addressed, and the harmonics of the disorder-averaged current (which is 1/2${\mathrm{\ensuremath{\Phi}}}_{0}$ periodic) are obtained. The orbital susceptibility of a mesoscopic system, disorder averaged over the canonical ensemble, may be large and positive, even for systems which, on a larger scale, should exhibit Landau diamagnetism.
TL;DR: A novel aspheric holographic optical element, the holographic axilens, is reported for achieving extended focal depth while keeping high lateral resolution.
Abstract: We report a novel aspheric holographic optical element, the holographic axilens, for achieving extended focal depth while keeping high lateral resolution. The element is designed according to special optimization techniques and recorded as a computer-generated hologram. The results for a specific element, which has a depth of focus of 30 mm, a lateral resolution of 80 microm, a focal length of 1250 mm, and a diameter of 12.5 mm at a wavelength of 633 nm, are presented.
TL;DR: The ability of phorbol esters to bind to and stimulate the kinase activity of PKC-L was revealed by introducing the cDNA into COS cells, and its tissue distribution is different from that described for other mammalian members of the PKC gene family.
Abstract: We have isolated and characterized a new human cDNA, coding for a protein kinase, related to the protein kinase C (PKC) gene family. Although this protein kinase shares some homologous sequences and structural features with the four members of the PKC family initially isolated (alpha, beta I, beta II, and gamma), it shows more homology with the recently described PKC-related subfamily, encoded by the cDNAs delta, epsilon, and zeta. The transcript for this gene product, termed PKC-L, is most abundant in lung tissue, less expressed in heart and skin tissue, and exhibited very low expression in brain tissue. Thus, its tissue distribution is different from that described for other mammalian members of the PKC gene family, their expression being enriched in brain tissues. PKC-L is also expressed in several human cell lines, including the human epidermoid carcinoma line A431. The ability of phorbol esters to bind to and stimulate the kinase activity of PKC-L was revealed by introducing the cDNA into COS cells.