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Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting over five million people globally and has no established cure. Current AD-related treatments only alleviate cognitive and behavioral symptoms and do not address disease onset or progression, underlining the unmet need to create an effective, innovative AD therapeutic. Extracellular vesicles (EVs) have emerged as a new class of nanotherapeutics. These secreted, lipid-bound cellular signaling carriers show promise for potential clinical applications for neurodegenerative diseases like AD. Additionally, analyzing contents and characteristics of patient-derived EVs may address the unmet need for earlier AD diagnostic techniques, informing physicians of altered genetic expression or cellular communications specific to healthy and diseased physiological states. There are numerous recent advances in regenerative medicine using EVs and include bioengineering perspectives to modify EVs, target glial cells in neurodegenerative diseases like AD, and potentially use EVs to diagnose and treat AD earlier. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development.

Sequence analysis frequently requires intuitive understanding and convenient representation of motifs. Typically, motifs are represented as position weight matrices (PWMs) and visualized using sequence logos. However, in many scenarios, representing motifs by wildcard-style consensus sequences is compact and sufficient for interpreting the motif information and search for motif match. Based on mutual information theory and Jenson-Shannon Divergence, we propose a mathematical framework to minimize the information loss in converting PWMs to consensus sequences. We name this representation as sequence Motto and have implemented an efficient algorithm with flexible options for converting motif PWMs into Motto from nucleotides, amino acids, and customized alphabets. Here we show that this representation provides a simple and efficient way to identify the binding sites of 1156 common TFs in the human genome. The effectiveness of the method was benchmarked by comparing sequence matches found by Motto with PWM scanning results found by FIMO. On average, our method achieves 0.81 area under the precision-recall curve, significantly (p-value < 0.01) outperforming all existing methods, including maximal positional weight, Douglas and minimal mean square error. We believe this representation provides a distilled summary of a motif, as well as the statistical justification.AVAILABILITYMotto is freely available at http://wanglab.ucsd.edu/star/motto.

Superhydrophobic coatings find important applications in consumer, commercial and advanced materials industries. Despite the existing approaches, the variety of substrates and different coating compositions necessitates the availability of several simple and versatile strategies for creating these functional coatings. This work demonstrates a facile and versatile strategy for achieving superhydrophobic coatings via deposition of modified polyvinylidene fluoride (m-PVDF) microparticles and subsequent thiol-ene surface functionalization of the microparticles with perfluorodecyl-1-thiol. The “ene” functionalities of the m-PVDF microparticles are achieved via dehydrofluorination of PVDF. The obtained coatings exhibit up to 160° static water contact angle. We show that the hydrophobic properties of the coatings are dependent upon the surface coverage of the substrate with the microparticles and the functionalization with the perfluorodecyl groups. Raman spectroscopy was used to provide insight into the thiol-ene functionalization of the superhydrophobic coatings.

Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans. Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency.

Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans. Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency.

The first highly enantioselective catalytic protocol for the reductive coupling of ketones and hydrazones is reported. These reactions proceed through neutral ketyl radical intermediates generated via a concerted proton-coupled electron transfer (PCET) event jointly mediated by a chiral phosphoric acid catalyst and the photoredox catalyst Ir(ppy)2(dtbpy)PF6. Remarkably, these neutral ketyl radicals appear to remain H-bonded to the chiral conjugate base of the Brønsted acid during the course of a subsequent C-C bond-forming step, furnishing syn 1,2-amino alcohol derivatives with excellent levels of diastereo- and enantioselectivity. This work provides the first demonstration of the feasibility and potential benefits of concerted PCET activation in asymmetric catalysis.

Aryl alkyl ethers, which are widely used throughout the chemical industry, are typically produced via the Williamson ether synthesis. Olefin hydroaryloxylation potentially offers a much more atom-economical alternative. Known acidic catalysts for hydroaryloxylation, however, afford very poor selectivity. We report the organometallic-catalyzed intermolecular hydroaryloxylation of unactivated olefins by iridium "pincer" complexes. These catalysts do not operate via the hidden Brønsted acid pathway common to previously developed transition-metal-based catalysts. The reaction is proposed to proceed via olefin insertion into an iridium-alkoxide bond, followed by rate-determining C-H reductive elimination to yield the ether product. The reaction is highly chemo- and regioselective and offers a new approach to the atom-economical synthesis of industrially important ethers and, potentially, a wide range of other oxygenates.

A pincer-ligated iridium complex, (PCP)Ir (PCP = κ(3)-C6H3-2,6-[CH2P(t-Bu)2]2), is found to undergo oxidative addition of C(sp(3))-O bonds of methyl esters (CH3-O2CR'), methyl tosylate (CH3-OTs), and certain electron-poor methyl aryl ethers (CH3-OAr). DFT calculations and mechanistic studies indicate that the reactions proceed via oxidative addition of C-H bonds followed by oxygenate migration, rather than by direct C-O addition. Thus, methyl aryl ethers react via addition of the methoxy C-H bond, followed by α-aryloxide migration to give cis-(PCP)Ir(H)(CH2)(OAr), followed by iridium-to-methylidene hydride migration to give (PCP)Ir(CH3)(OAr). Methyl acetate undergoes C-H bond addition at the carbomethoxy group to give (PCP)Ir(H)[κ(2)-CH2OC(O)Me] which then affords (PCP-CH2)Ir(H)(κ(2)-O2CMe) (6-Me) in which the methoxy C-O bond has been cleaved, and the methylene derived from the methoxy group has migrated into the PCP Cipso-Ir bond. Thermolysis of 6-Me ultimately gives (PCP)Ir(CH3)(κ(2)-O2CR), the net product of methoxy group C-O oxidative addition. Reaction of (PCP)Ir with species of the type ROAr, RO2CMe or ROTs, where R possesses β-C-H bonds (e.g., R = ethyl or isopropyl), results in formation of (PCP)Ir(H)(OAr), (PCP)Ir(H)(O2CMe), or (PCP)Ir(H)(OTs), respectively, along with the corresponding olefin or (PCP)Ir(olefin) complex. Like the C-O bond oxidative additions, these reactions also proceed via initial activation of a C-H bond; in this case, C-H addition at the β-position is followed by β-migration of the aryloxide, carboxylate, or tosylate group. Calculations indicate that the β-migration of the carboxylate group proceeds via an unusual six-membered cyclic transition state in which the alkoxy C-O bond is cleaved with no direct participation by the iridium center.

β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyze their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Coproduction of MBLs and SBLs in resistant infections is thus of major clinical concern. The development of “dual-action” inhibitors, targeting both SBLs and MBLs, is of interest, but this is considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactamases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase CTX-M-15, the class C enzyme AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolyzing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small-molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis.

A study of electronic factors governing the thermodynamics of C-H and N-H bond addition to Ir(I) complexes was conducted. DFT calculations were performed on an extensive series of trans-(PH3)2IrXL complexes (L = NH3 and CO; X = various monodentate ligands) to parametrize the relative σ- and π-donating/withdrawing properties of the various ligands, X. Computed energies of oxidative addition of methane to a series of three- and four-coordinate Ir(I) complexes bearing an ancillary ligand, X, were correlated with the resulting (σ(X), π(X)) parameter set. Regression analysis indicates that the thermodynamics of addition of methane to trans-(PH3)2IrX are generally strongly disfavored by increased σ-donation from the ligand X, in contradiction to widely held views on oxidative addition. The trend for oxidative addition of methane to four-coordinate Ir(I) was closely related to that observed for the three-coordinate complexes, albeit slightly more complicated. The computational analysis was found to be consistent with the rates of reductive elimination of benzene from a series of isoelectronic Ir(III) phenyl hydride complexes, measured experimentally in this work and previously reported. Extending the analysis of ancillary ligand energetic effects to the oxidative addition of ammonia to three-coordinate Ir(I) complexes leads to the conclusion that increasing σ-donation by X also disfavors oxidative addition of N-H bonds to trans-(PH3)2IrX. However, coordination of NH3 to the Ir(I) center is disfavored even more strongly by increasing σ-donation by X, which explains why the few documented examples of H-NH2 oxidative addition to transition metals involve complexes with strongly σ-donating ligands situated trans to the site of addition. An orbital-based rationale for the observed results is presented.

Carbon-fluorine bonds are the strongest known single bonds to carbon and as a consequence can prove very hard to cleave. Alhough vinyl and aryl C-F bonds can undergo oxidative addition to transition metal complexes, this reaction has appeared inoperable with aliphatic substrates. We report the addition of C(sp(3))-F bonds (including alkyl-F) to an iridium center via the initial, reversible cleavage of a C-H bond. These results suggest a distinct strategy for the development of catalysts and promoters to make and break C-F bonds, which are of strong interest in the context of both pharmaceutical and environmental chemistry.

The transfer dehydrogenation of several ketones by (PCP)IrH2 (PCP = κ3-C6H3-2,6-(CH2PtBu2)2) (1) has been observed. Catalytic turnover was inhibited in most cases by the formation of stable metallacycles or the O–H oxidative addition of phenolic products. Catalytic transfer dehydrogenation of 3,3-dimethylcyclohexanone was achieved, giving the corresponding α,β-enone. The transfer dehydrogenation reaction of cycloheptanone with 1 was found to generate a surprisingly stable PCP-iridium troponyl hydride (9), which is stabilized by conjugation and possibly represents an unusual bicyclo[5.2.0]troponyliridium metalloaromatic structure. Complex 9 was found to catalyze the dimerization of tropone to give a fused tricyclic dihydrodicycloheptafuranol. A mechanism for this reaction is proposed wherein the coordinated troponyl group nucleophilically attacks a free tropone molecule.

Summary Seismic anisotropy is sensitive to the intensity and orientation of fractures aligned by tectonic or local stress fields. Azimuthal anisotropy of amplitude vs. offset (AzAVO) is one common measure of seismic anisotropy for fracture detection. For this study, we calculated P-wave AzAVO attributes for a Lower Cretaceous limestone reservoir in east Texas. Our study tests AzAVO inversion for the relatively low-fold, fair data quality typical of some land surveys. We developed a workflow to integrate the AzAVO inversion with rock physics, forward seismic modeling, seismic-scale fault interpretation, image logs, and cores. Our AzAVO inversion method was based on Rüger's equation, which describes the observed reflectivity (R) as a function of incidence angle (θi) and acquisition azimuth (ϕi) to equal a function of normal incidence reflectivity (A0), amplitude vs. offset (AVO) slope (B0), anisotropy magnitude (B1), orientation of symmetry of anisotropy (ϕ0), and noise (ni ): (1) R ( θ i , ϕ i ) ≈ A 0 + [ B 0 + B 1 cos 2 ( ϕ i + ϕ 0 ) ] sin 2 θ i + n i , Inversion of Rüger's equation yielded four attribute volumes (corresponding to A0, B0, B1, and ϕ0). Additionally, we proposed an additional data-quality parameter that describes the relative amount of the total reflection energy predicted by the model. Pre-inversion processing carefully preserved signal via random noise attenuation, superbinning, bandwidth balancing, and phase alignment. In general, AzAVO inversion displayed geologically interpret-able high-anisotropy anomalies. Noise, however, limited our confidence for quantitative fracture prediction. On the flanks of the anticline, data quality was high (greater than 50% fit of observed to predicted amplitude). Here the magnitude of the anisotropy (B1) volume showed strong lineations parallel to northeast-southwest trending faults. Over the crest of the anticline, the inversion quality was degraded by an overburden effect, coincident with poor data quality (less than 50% fit). AzAVO orientation maps were noisy and in some places obscured by an acquisition footprint. Locally, however, AzAVO orientations were parallel to east-northeast fracture orientations from cores, maximum horizontal stress from image logs, and fast-velocity direction from a dipole-sonic log.

Black hat search engine optimization (SEO), the practice of abusively manipulating search results, is an enticing method to acquire targeted user traffic. In turn, a range of interventions--from modifying search results to seizing domains--are used to combat this activity. In this paper, we examine the effectiveness of these interventions in the context of an understudied market niche, counterfeit luxury goods. Using eight months of empirical crawled data, we identify 52 distinct SEO campaigns, document how well they are able to place search results for sixteen luxury brands, how this capability impacts the dynamics of their order volumes and how well existing interventions undermine this business when employed.

The method is the first example of the highly enantioselective reductive coupling of ketones and hydrazones reported to date.

New carbazolide-based iridium pincer complexes ((carb)PNP)Ir(C2H4), 3a, and ((carb)PNP)Ir(H)2, 3b, have been prepared and characterized. The dihydride, 3b, reacts with ethylene to yield the cis-dihydride ethylene complex cis-((carb)PNP)Ir(C2H4)(H)2. Under ethylene this complex reacts slowly at 70 °C to yield ethane and the ethylene complex, 3a. Kinetic analysis establishes that the reaction rate is dependent on ethylene concentration and labeling studies show reversible migratory insertion to form an ethyl hydride complex prior to formation of 3a. Exposure of cis-((carb)PNP)Ir(C2H4)(H)2 to hydrogen results in very rapid formation of ethane and dihydride, 3b. DFT analysis suggests that ethane elimination from the ethyl hydride complex is assisted by ethylene through formation of ((carb)PNP)Ir(H)(Et)(C2H4) and by H2 through formation of ((carb)PNP)Ir(H)(Et)(H2). Elimination of ethane from Ir(III) complex ((carb)PNP)Ir(H)(Et)(H2) is calculated to proceed through an Ir(V) complex ((carb)PNP)Ir(H)3(Et) which reductively eliminates ethane with a very low barrier to return to the Ir(III) dihydride, 3b. Under catalytic hydrogenation conditions (C2H4/H2), cis-((carb)PNP)Ir(C2H4)(H)2 is the catalyst resting state, and the catalysis proceeds via an Ir(III)/Ir(V)/Ir(III) cycle. This is in sharp contrast to isoelectronic (PCP)Ir systems in which hydrogenation proceeds through an Ir(III)/Ir(I)/Ir(III) cycle. The basis for this remarkable difference is discussed.

Aryl alkyl ethers, which are widely used throughout the chemical industry, are typically produced via the Williamson ether synthesis. Olefin hydroaryloxylation potentially offers a much more atom-economical alternative. Known acidic catalysts for hydroaryloxylation, however, afford very poor selectivity. We report the organometallic-catalyzed intermolecular hydroaryloxylation of unactivated olefins by iridium “pincer” complexes. These catalysts do not operate via the hidden Bronsted acid pathway common to previously developed transition-metal-based catalysts. The reaction is proposed to proceed via olefin insertion into an iridium–alkoxide bond, followed by rate-determining C–H reductive elimination to yield the ether product. The reaction is highly chemo- and regioselective and offers a new approach to the atom-economical synthesis of industrially important ethers and, potentially, a wide range of other oxygenates.

Cloaking is a common 'bait-and-switch' technique used to hide the true nature of a Web site by delivering blatantly different semantic content to different user segments. It is often used in search engine optimization (SEO) to obtain user traffic illegitimately for scams. In this paper, we measure and characterize the prevalence of cloaking on different search engines, how this behavior changes for targeted versus untargeted advertising and ultimately the response to site cloaking by search engine providers. Using a custom crawler, called Dagger, we track both popular search terms (e.g., as identified by Google, Alexa and Twitter) and targeted keywords (focused on pharmaceutical products) for over five months, identifying when distinct results were provided to crawlers and browsers. We further track the lifetime of cloaked search results as well as the sites they point to, demonstrating that cloakers can expect to maintain their pages in search results for several days on popular search engines and maintain the pages themselves for longer still.

Seismic reflection amplitude at the top of a fractured rock layer varies as a function of both offset and azimuth. Travel time and attenuation along ray paths through a fractured layer also vary with offset and azimuth. An integrated set of procedures and a flexible workflow were developed to extract these measures of azimuthal seismic anisotropy. The procedures include screening tools to evaluate the feasibility of applying seismic inversion methods to extract azimuthal attributes, and quick-look tools to rapidly visualize seismic anisotropy that may indicate open fractures. Azimuthal anisotropy is recognized in seismic data from a giant Middle East oil field by identifying differences between sector stacks formed from different azimuth bins. This screening analysis shows an azimuthal AVO response that seems to vary in a meaningful way across the field. Further analysis utilized a proprietary, azimuthal AVO, inversion process that estimates two attributes. The first quantifies AVO anisotropy that may be related to fracture intensity, differential stress, significant stratal dips, or other factors. The second attribute is related to fracture orientation when fractures are the cause of anomalies. A goodness-of-fit estimate quantifies the error between the fitting function and the observed data. Inversion results show areas with strong azimuthal variations that correspond well with coherent energy observed in the sector stack difference, but with improved spatial resolution and contrast. The key to using azimuthal seismic anomalies wisely in reservoir development is their integration with subsurface data to discriminate among possible sources of the anomalies. The validation phase of the study used subsurface data on fracture intensity, in-situ stress state, stratal geometry, erosion surfaces, and production data and tests. Maps of seismic anisotropy show coherent anomalies related to known geologic features, giving confidence that the method detects meaningful geologic information that can be used to constrain reservoir quality models.

Summary We present a case study where we calculated P-wave seismic anisotropy for a land, 3D seismic survey at a gas field in east Texas. We calculated the azimuthal AVO (AzAVO) and azimuthal velocity (AzNMO) anisotropy. We compared the results with interpreted faults, fractures from oriented core, image logs, present day stress, and a dipole sonic log. High- anisotropy anomalies align with faults on the flanks of the structure. Low seismic anisotropy characterizes the crest of the structure, and may be an artifact of an associated amplitude shadow. Locally, orientations predicted from seismic anisotropy agree with our subsurface fracture observations. Full quantitative fracture interpretation is restricted, however, by signal noise, local reduction in inversion quality by an amplitude artifact, and limited subsurface fracture correlation.

Even for gentle structures, seismic energy does not reflect from points directly below the source and receiver midpoint. Data must be migrated using a velocity model so that reflectors are positioned at their true spatial locations. In the usual Kirchhoff method of depth migration, we assume that a single first-arrival raypath (and traveltime) connects a source (or receiver) location to each point in the subsurface and the migration is straightforward. However, in areas of complex velocity structure, such as near a GOM salt body, seismic energy can travel from the surface to a subsurface point in a variety of raypaths and therefore may have multiple arrivals. The first arrivals do not necessarily carry most of the seismic energy. Migration results using traveltimes for different arrivals can be quite different. In this paper, we will show that the depth image around a GOM salt body is improved by using the "maximum energy" traveltimes instead of the first-arrival traveltimes. Furthermore, the improvements are related to the geometry of the data acquisition relative to the salt body. The largest improvements are seen when the data are collected in a direction tangent to the salt body.

We report on the synthesis and reactivity of rhodium complexes featuring bulky, neutral pincer ligands with a “POP” coordinating motif, tBuxanPOP, iPrxanPOP, and tBufurPOP (tBuxanPOP = 4,5-bis(di-tert-butylphosphino)-9,9-dimethyl-9H-xanthene; iPrxanPOP = 4,5-bis(diisopropylphosphino)-9,9-dimethyl-9H-xanthene; tBufurPOP = 2,5-bis((di-tert-butylphosphino)methyl)furan). The (POP)Rh complexes described in this work are, in general, more reactive than their (PNP)Rh and (PCP)Rh analogues, which allows for the generation of several new species under relatively mild conditions. Thus, monomeric (POP)RhCl complexes oxidatively add H2 to form (POP)Rh(H)2Cl, from which the coordinatively unsaturated hydride complexes (POP)Rh(H)2+ and (tBuxanPOP)Rh(H) can be obtained. In the case of the new ligand tBufurPOP, a major kinetic product of the reaction with H2 is, surprisingly, the trans dihydride, i.e. trans-(tBufurPOP)Rh(H)2Cl; this is most likely attributable to reversible decoordination of one of the pincer coordinating groups, followed by addition of H2 to a highly reactive three-coordinate species. Ethylene is hydrogenated by (tBuxanPOP)Rh(H)2+ at 25 °C, but propylene is not, even at elevated temperatures. Ethylene undergoes insertion into the Rh–H bond of (tBuxanPOP)RhH; this reaction is reversible, allowing for an experimental determination of the equilibrium constant for this hydrometalation. The less bulky iPrxanPOP ligand affords a dihydride complex which functions as a modestly active alkane dehydrogenation catalyst, the first such example for a cationic pincer complex of any metal.

After a decade of research and evaluation, a number of contractors and major oil companies have deployed massively parallel computers for production seismic processing. These investments both in hardware and in software development have been made despite disagreement among vendors over the best parallel architecture, a sense within the computer science community that automatic parallelization remains an unsolved problem, a relative inattention to parallel I/O and mass storage issues important to seismic processing, and close management scrutiny of the value added by high-end processing algorithms. Most of the issues raised by the supercomputing community have proved to be irrelevant to seismic processing: processor topology, code portability, ease-of-use, and scalability do not significantly impact our use of high-performance computers. The turning point came when our industry realized that only a few relevant issues remained: applicability, stability, and the programming paradigm. These have now been addressed by business trends, product maturity, and hard work. The idiosyncrasies of our business (the need to recognize and manage risk and the tremendous leveraging that occurs between research and successful exploration) have placed us among the earliest adopters of parallel computing technology. These idiosyncrasies are unlikely to change and will therefore continue to distinguish our usemore » of advanced technology from the way in which it is adopted by other industries.« less

We describe a novel method of determining potentially successful starting designs by utilizing an expert systems algorithm which operates on a database of previously well-designed optical systems. The database is composed of systems created by a `not-so-local' optimization algorithm, and a collection of previously well-designed systems. The expert system is unique in its ability to modify the number of optical elements to create new starting points. The `not- so-local' optimization algorithm combines the downhhll simplex method with a random multi- start algorithm which can create new optical systems for inclusion into the expert system database. This creates a diversity which can be used to synthesize unexpected starting designs.

We have developed a method for the spherical divergence correction of seismic reflection data based on normal moveout and stacking of cylindrical slant stacks. The method is illustrated on some Gulf of Mexico data. The results show that our method yields essentially the same traveltime information as does conventional processing. Our amplitudes, however, are more interpretable in terms of reflectivity than are those obtained by using an empirical spherical divergence correction.