TY - CONF AB - Games played on graphs may have qualitative objectives, such as the satisfaction of an ω-regular property, or quantitative objectives, such as the optimization of a real-valued reward. When games are used to model reactive systems with both fairness assumptions and quantitative (e.g., resource) constraints, then the corresponding objective combines both a qualitative and a quantitative component. In a general case of interest, the qualitative component is a parity condition and the quantitative component is a mean-payoff reward. We study and solve such mean-payoff parity games. We also prove some interesting facts about mean-payoff parity games which distinguish them both from mean-payoff and from parity games. In particular, we show that optimal strategies exist in mean-payoff parity games, but they may require infinite memory. AU - Krishnendu Chatterjee AU - Thomas Henzinger AU - Jurdziński, Marcin ID - 4554 TI - Mean-payoff parity games ER - TY - CONF AB - We define and study a quantitative generalization of the traditional boolean framework of model-based specification and verification. In our setting, propositions have integer values at states, and properties have integer values on traces. For example, the value of a quantitative proposition at a state may represent power consumed at the state, and the value of a quantitative property on a trace may represent energy used along the trace. The value of a quantitative property at a state, then, is the maximum (or minimum) value achievable over all possible traces from the state. In this framework, model checking can be used to compute, for example, the minimum battery capacity necessary for achieving a given objective, or the maximal achievable lifetime of a system with a given initial battery capacity. In the case of open systems, these problems require the solution of games with integer values. Quantitative model checking and game solving is undecidable, except if bounds on the computation can be found. Indeed, many interesting quantitative properties, like minimal necessary battery capacity and maximal achievable lifetime, can be naturally specified by quantitative-bound automata, which are finite automata with integer registers whose analysis is constrained by a bound function f that maps each system K to an integer f(K). Along with the linear-time, automaton-based view of quantitative verification, we present a corresponding branching-time view based on a quantitative-bound μ-calculus, and we study the relationship, expressive power, and complexity of both views. AU - Chakrabarti, Arindam AU - Krishnendu Chatterjee AU - Thomas Henzinger AU - Kupferman, Orna AU - Majumdar, Ritankar S ID - 4560 TI - Verifying quantitative properties using bound functions VL - 3725 ER - TY - CONF AB - Planning in adversarial and uncertain environments can be modeled as the problem of devising strategies in stochastic perfect information games. These games are generalizations of Markov decision processes (MDPs): there are two (adversarial) players, and a source of randomness. The main practical obstacle to computing winning strategies in such games is the size of the state space. In practice therefore, one typically works with abstractions of the model. The diffculty is to come up with an abstraction that is neither too coarse to remove all winning strategies (plans), nor too fine to be intractable. In verification, the paradigm of counterexample-guided abstraction refinement has been successful to construct useful but parsimonious abstractions automatically. We extend this paradigm to probabilistic models (namely, perfect information games and, as a special case, MDPs). This allows us to apply the counterexample-guided abstraction paradigm to the AI planning problem. As special cases, we get planning algorithms for MDPs and deterministic systems that automatically construct system abstractions. AU - Krishnendu Chatterjee AU - Thomas Henzinger AU - Jhala, Ranjit AU - Majumdar, Ritankar S ID - 4557 TI - Counterexample-guided planning ER - TY - CONF AB - BLAST is an automatic verification tool for checking temporal safety properties of C programs. Given a C program and a temporal safety property, BLAST statically proves that either the program satisfies the safety property or the program has an execution trace that exhibits a violation of the property. BLAST constructs, explores, and refines abstractions of the program state space based on lazy predicate abstraction and interpolation-based predicate discovery. We show how BLAST can be used to statically prove memory safety for C programs. We take a two-step approach. First, we use Ccured, a type-based memory safety analyzer, to annotate with run-time checks all program points that cannot be proved memory safe by the type system. Second, we use BLAST to remove as many of the run-time checks as possible (by proving that these checks never fail), and to generate for the remaining run-time checks execution traces that witness them fail. Our experience shows that BLAST can remove many of the run-time checks added by Ccured and provide useful information to the programmer about many of the remaining checks. AU - Beyer, Dirk AU - Thomas Henzinger AU - Jhala, Ranjit AU - Majumdar, Ritankar S ID - 4579 TI - Checking memory safety with BLAST VL - 3442 ER - TY - CONF AB - We present a language for specifying web service interfaces. A web service interface puts three kinds of constraints on the users of the service. First, the interface specifies the methods that can be called by a client, together with types of input and output parameters; these are called signature constraints. Second, the interface may specify propositional constraints on method calls and output values that may oc- cur in a web service conversation; these are called consis- tency constraints. Third, the interface may specify temporal constraints on the ordering of method calls; these are called protocol constraints. The interfaces can be used to check, first, if two or more web services are compatible, and second, if a web service A can be safely substituted for a web ser- vice B. The algorithm for compatibility checking verifies that two or more interfaces fulfill each others’ constraints. The algorithm for substitutivity checking verifies that service A demands fewer and fulfills more constraints than service B. AU - Beyer, Dirk AU - Chakrabarti, Arindam AU - Thomas Henzinger ID - 4576 TI - Web service interfaces ER - TY - JOUR AB - Temporal logic is two-valued: formulas are interpreted as either true or false. When applied to the analysis of stochastic systems, or systems with imprecise formal models, temporal logic is therefore fragile: even small changes in the model can lead to opposite truth values for a specification. We present a generalization of the branching-time logic CTL which achieves robustness with respect to model perturbations by giving a quantitative interpretation to predicates and logical operators, and by discounting the importance of events according to how late they occur. In every state, the value of a formula is a real number in the interval [0,1], where 1 corresponds to truth and 0 to falsehood. The boolean operators and and or are replaced by min and max, the path quantifiers ∃ and ∀ determine sup and inf over all paths from a given state, and the temporal operators ⋄ and □ specify sup and inf over a given path; a new operator averages all values along a path. Furthermore, all path operators are discounted by a parameter that can be chosen to give more weight to states that are closer to the beginning of the path. We interpret the resulting logic DCTL over transition systems, Markov chains, and Markov decision processes. We present two semantics for DCTL: a path semantics, inspired by the standard interpretation of state and path formulas in CTL, and a fixpoint semantics, inspired by the μ-calculus evaluation of CTL formulas. We show that, while these semantics coincide for CTL, they differ for DCTL, and we provide model-checking algorithms for both semantics. AU - de Alfaro, Luca AU - Faella, Marco AU - Thomas Henzinger AU - Majumdar, Ritankar S AU - Stoelinga, Mariëlle ID - 4625 IS - 1 JF - Theoretical Computer Science TI - Model checking discounted temporal properties VL - 345 ER - TY - CONF AB - Surveying results from [5] and [6], we motivate and introduce the theory behind formalizing rich interfaces for software and hardware components. Rich interfaces specify the protocol aspects of component interaction. Their formalization, called interface automata, permits a compiler to check the compatibility of component interaction protocols. Interface automata support incremental design and independent implementability. Incremental design means that the compatibility checking of interfaces can proceed for partial system descriptions, without knowing the interfaces of all components. Independent implementability means that compatible interfaces can be refined separately, while still maintaining compatibility. AU - de Alfaro, Luca AU - Thomas Henzinger ID - 4624 TI - Interface-based design VL - 195 ER - TY - CONF AB - We present the first demonstration of Jozsa's "counterfactual computation", using an optical Grover's search algorithm. We put the algorithm in a superposition of 'running' and 'not-running', obtaining information even though the algorithm does not run. AU - Onur Hosten AU - Rakher, Matthew T AU - Barreiro, Julio T AU - Peters, Nicholas A AU - Kwiat, Paul G ID - 575 TI - Counterfactual quantum computation VL - 1 ER - TY - JOUR AB - A current challenge in neuroscience is to bridge the gaps between genes, proteins, neurons, neural circuits, and behavior in a single animal model. The nematode Caenorhabditis elegans has unique features that facilitate this synthesis. Its nervous system includes exactly 302 neurons, and their pattern of synaptic connectivity is known. With only five olfactory neurons, C. elegans can dynamically respond to dozens of attractive and repellant odors. Thermosensory neurons enable the nematode to remember its cultivation temperature and to track narrow isotherms. Polymodal sensory neurons detect a wide range of nociceptive cues and signal robust escape responses. Pairing of sensory stimuli leads to long-lived changes in behavior consistent with associative learning. Worms exhibit social behaviors and complex ultradian rhythms driven by Ca2+ oscillators with clock-like properties. Genetic analysis has identified gene products required for nervous system function and elucidated the molecular and neural bases of behaviors. AU - de Bono, Mario AU - Villu Maricq, Andres ID - 6153 JF - Annual Review of Neuroscience SN - 0147-006X TI - Neuronal substrates of complex behaviors in C. elegans VL - 28 ER - TY - JOUR AU - Cheung, Benny H.H. AU - Cohen, Merav AU - Rogers, Candida AU - Albayram, Onder AU - de Bono, Mario ID - 6154 IS - 10 JF - Current Biology SN - 0960-9822 TI - Experience-dependent modulation of C. elegans behavior by ambient oxygen VL - 15 ER - TY - JOUR AB - Transmission of signals within the brain is essential for cognitive function, but it is not clear how neural circuits support reliable and accurate signal propagation over a sufficiently large dynamic range. Two modes of propagation have been studied: synfire chains, in which synchronous activity travels through feedforward layers of a neuronal network, and the propagation of fluctuations in firing rate across these layers. In both cases, a sufficient amount of noise, which was added to previous models from an external source, had to be included to support stable propagation. Sparse, randomly connected networks of spiking model neurons can generate chaotic patterns of activity. We investigate whether this activity, which is a more realistic noise source, is sufficient to allow for signal transmission. We find that, for rate-coded signals but not for synfire chains, such networks support robust and accurate signal reproduction through up to six layers if appropriate adjustments are made in synaptic strengths. We investigate the factors affecting transmission and show that multiple signals can propagate simultaneously along different pathways. Using this feature, we show how different types of logic gates can arise within the architecture of the random network through the strengthening of specific synapses. AU - Vogels, Tim P AU - Abbott, L. F. ID - 8028 IS - 46 JF - Journal of Neuroscience SN - 0270-6474 TI - Signal propagation and logic gating in networks of integrate-and-fire neurons VL - 25 ER - TY - JOUR AB - Neural network modeling is often concerned with stimulus-driven responses, but most of the activity in the brain is internally generated. Here, we review network models of internally generated activity, focusing on three types of network dynamics: (a) sustained responses to transient stimuli, which provide a model of working memory; (b) oscillatory network activity; and (c) chaotic activity, which models complex patterns of background spiking in cortical and other circuits. We also review propagation of stimulus-driven activity through spontaneously active networks. Exploring these aspects of neural network dynamics is critical for understanding how neural circuits produce cognitive function. AU - Vogels, Tim P AU - Rajan, Kanaka AU - Abbott, L.F. ID - 8029 IS - 1 JF - Annual Review of Neuroscience SN - 0147-006X TI - Neural network dynamics VL - 28 ER - TY - JOUR AB - Cytosine DNA methylation in vertebrates is widespread, but methylation in plants is found almost exclusively at transposable elements and repetitive DNA [1]. Within regions of methylation, methylcytosines are typically found in CG, CNG, and asymmetric contexts. CG sites are maintained by a plant homolog of mammalian Dnmt1 acting on hemi-methylated DNA after replication. Methylation of CNG and asymmetric sites appears to be maintained at each cell cycle by other mechanisms. We report a new type of DNA methylation in Arabidopsis, dense CG methylation clusters found at scattered sites throughout the genome. These clusters lack non-CG methylation and are preferentially found in genes, although they are relatively deficient toward the 5′ end. CG methylation clusters are present in lines derived from different accessions and in mutants that eliminate de novo methylation, indicating that CG methylation clusters are stably maintained at specific sites. Because 5-methylcytosine is mutagenic, the appearance of CG methylation clusters over evolutionary time predicts a genome-wide deficiency of CG dinucleotides and an excess of C(A/T)G trinucleotides within transcribed regions. This is exactly what we find, implying that CG methylation clusters have contributed profoundly to plant gene evolution. We suggest that CG methylation clusters silence cryptic promoters that arise sporadically within transcription units. AU - Tran, Robert K. AU - Henikoff, Jorja G. AU - Zilberman, Daniel AU - Ditt, Renata F. AU - Jacobsen, Steven E. AU - Henikoff, Steven ID - 9491 IS - 2 JF - Current Biology SN - 0960-9822 TI - DNA methylation profiling identifies CG methylation clusters in Arabidopsis genes VL - 15 ER - TY - JOUR AB - Background: DNA methylation occurs at preferred sites in eukaryotes. In Arabidopsis, DNA cytosine methylation is maintained by three subfamilies of methyltransferases with distinct substrate specificities and different modes of action. Targeting of cytosine methylation at selected loci has been found to sometimes involve histone H3 methylation and small interfering (si)RNAs. However, the relationship between different cytosine methylation pathways and their preferred targets is not known. Results: We used a microarray-based profiling method to explore the involvement of Arabidopsis CMT3 and DRM DNA methyltransferases, a histone H3 lysine-9 methyltransferase (KYP) and an Argonaute-related siRNA silencing component (AGO4) in methylating target loci. We found that KYP targets are also CMT3 targets, suggesting that histone methylation maintains CNG methylation genome-wide. CMT3 and KYP targets show similar proximal distributions that correspond to the overall distribution of transposable elements of all types, whereas DRM targets are distributed more distally along the chromosome. We find an inverse relationship between element size and loss of methylation in ago4 and drm mutants. Conclusion: We conclude that the targets of both DNA methylation and histone H3K9 methylation pathways are transposable elements genome-wide, irrespective of element type and position. Our findings also suggest that RNA-directed DNA methylation is required to silence isolated elements that may be too small to be maintained in a silent state by a chromatin-based mechanism alone. Thus, parallel pathways would be needed to maintain silencing of transposable elements. AU - Tran, Robert K. AU - Zilberman, Daniel AU - de Bustos, Cecilia AU - Ditt, Renata F. AU - Henikoff, Jorja G. AU - Lindroth, Anders M. AU - Delrow, Jeffrey AU - Boyle, Tom AU - Kwong, Samson AU - Bryson, Terri D. AU - Jacobsen, Steven E. AU - Henikoff, Steven ID - 9514 IS - 11 JF - Genome Biology SN - 1474-760X TI - Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis VL - 6 ER - TY - JOUR AB - The impact of an amino acid replacement on the organism's fitness can vary from lethal to selectively neutral and even, in rare cases, beneficial. Substantial data are available on either pathogenic or acceptable replacements. However, the whole distribution of coefficients of selection against individual replacements is not known for any organism. To ascertain this distribution for human proteins, we combined data on pathogenic missense mutations, on human non-synonymous SNPs and on human-chimpanzee divergence of orthologous proteins. Fractions of amino acid replacements which reduce fitness by >10-2, 10-2-10-4, 10-4-10-5 and <10-5 are 25, 49, 14 and 12%, respectively. On average, the strength of selection against a replacement is substantially higher when chemically dissimilar amino acids are involved, and the Grantham's index of a replacement explains 35% of variance in the average logarithm of selection coefficients associated with different replacements. Still, the impact of a replacement depends on its context within the protein more than on its own nature. Reciprocal replacements are often associated with rather different selection coefficients, in particular, replacements of non-polar amino acids with polar ones are typically much more deleterious than replacements in the opposite direction. However, differences between evolutionary fluxes of reciprocal replacements are only weakly correlated with the differences between the corresponding selection coefficients. AU - Yampolsky, Lev Y AU - Fyodor Kondrashov AU - Kondrashov, Alexey S ID - 843 IS - 21 JF - Human Molecular Genetics TI - Distribution of the strength of selection against amino acid replacements in human proteins VL - 14 ER - TY - JOUR AB - Fast multidimensional NMR with a time resolution of a few seconds provides a new tool for high throughput screening and site-resolved real-time studies of kinetic molecular processes by NMR. Recently we have demonstrated the feasibility to record protein 1H–15N correlation spectra in a few seconds of acquisition time using a new SOFAST-HMQC experiment (Schanda and Brutscher (2005) J. Am. Chem. Soc. 127, 8014). Here, we investigate in detail the performance of SOFAST-HMQC to record 1H–15N and 1H−13C correlation spectra of proteins of different size and at different magnetic field strengths. Compared to standard 1H–15N correlation experiments SOFAST-HMQC provides a significant gain in sensitivity, especially for fast repetition rates. Guidelines are provided on how to set up SOFAST-HMQC experiments for a given protein sample. In addition, an alternative pulse scheme, IPAP-SOFAST-HMQC is presented that allows application on NMR spectrometers equipped with cryogenic probes, and fast measurement of one-bond 1H–13C and 1H–15N scalar and residual dipolar coupling constants. AU - Schanda, Paul AU - Kupče, Ēriks AU - Brutscher, Bernhard ID - 8491 IS - 4 JF - Journal of Biomolecular NMR KW - Spectroscopy KW - Biochemistry SN - 0925-2738 TI - SOFAST-HMQC experiments for recording two-dimensional deteronuclear correlation spectra of proteins within a few seconds VL - 33 ER - TY - JOUR AB - We demonstrate for different protein samples that 2D 1H−15N correlation NMR spectra can be recorded in a few seconds of acquisition time using a new band-selective optimized flip-angle short-transient heteronuclear multiple quantum coherence experiment. This has enabled us to measure fast hydrogen−deuterium exchange rate constants along the backbone of a small globular protein fragment by real-time 2D NMR. AU - Schanda, Paul AU - Brutscher, Bernhard ID - 8492 IS - 22 JF - Journal of the American Chemical Society KW - Colloid and Surface Chemistry KW - Biochemistry KW - General Chemistry KW - Catalysis SN - 0002-7863 TI - Very fast two-dimensional NMR spectroscopy for real-time investigation of dynamic events in proteins on the time scale of seconds VL - 127 ER - TY - JOUR AB - The purpose of this paper is to construct examples of diffusion for E-Hamiltonian perturbations of completely integrable Hamiltonian systems in 2d-dimensional phase space, with d large. In the first part of the paper, simple and explicit examples are constructed illustrating absence of ‘long-time’ stability for size E Hamiltonian perturbations of quasi-convex integrable systems already when the dimension 2d of phase space becomes as large as log 1/E . We first produce the example in Gevrey class and then a real analytic one, with some additional work. In the second part, we consider again E-Hamiltonian perturbations of completely integrable Hamiltonian system in 2d-dimensional space with E-small but not too small, |E| > exp(−d), with d the number of degrees of freedom assumed large. It is shown that for a class of analytic time-periodic perturbations, there exist linearly diffusing trajectories. The underlying idea for both examples is similar and consists in coupling a fixed degree of freedom with a large number of them. The procedure and analytical details are however significantly different. As mentioned, the construction in Part I is totally elementary while Part II is more involved, relying in particular on the theory of normally hyperbolic invariant manifolds, methods of generating functions, Aubry–Mather theory, and Mather’s variational methods. AU - Bourgain, Jean AU - Kaloshin, Vadim ID - 8516 IS - 1 JF - Journal of Functional Analysis KW - Analysis SN - 0022-1236 TI - On diffusion in high-dimensional Hamiltonian systems VL - 229 ER - TY - JOUR AB - Sequence analysis of protein and mitochondrially encoded tRNA genes shows that substitutions producing pathogenic effects in humans are often found in normal, healthy individuals from other species. Analysis of stability of protein and tRNA structures shows that the disease-causing effects of pathogenic mutations can be neutralized by other, compensatory substitutions that restore the structural stability of the molecule. Further study of such substitutions will, hopefully, lead to new methods for curing genetic dis- eases that may be based on the correction of molecule stability as a whole instead of reversing an individual pathogenic mutation. AU - Kondrashov, Fyodor ID - 877 IS - 3 JF - Biofizika TI - The analysis of monomer sequences in protein and tRNA and the manifestation of the compensation of pathogenic deviations in their evolution VL - 50 ER - TY - JOUR AB - Negative trade-offs are thought to be a pervasive phenomenon and to inhibit evolution at all levels. New evidence shows that at the molecular level, there may be no trade-offs preventing the emergence of an enzyme with multiple functions. AU - Fyodor Kondrashov ID - 878 IS - 1 JF - Nature Genetics TI - In search of the limits of evolution VL - 37 ER - TY - JOUR AB - Some mutations in human mitochondrial tRNAs are severely pathogenic. The available computational methods have a poor record of predicting the impact of a tRNA mutation on the phenotype and fitness. Here patterns of evolution at tRNA sites that harbor pathogenic mutations and at sites that harbor phenotypically cryptic polymorphisms were compared. Mutations that are pathogenic to humans occupy more conservative sites, are only rarely fixed in closely related species, and, when located in stem structures, often disrupt Watson-Crick pairing and display signs of compensatory evolution. These observations make it possible to classify ∼90% of all known pathogenic mutations as deleterious together with only ∼30% of polymorphisms. These polymorphisms segregate at frequencies that are more than two times lower than frequencies of polymorphisms classified as benign, indicating that at least ∼30% of known polymorphisms in mitochondrial tRNAs affect fitness negatively. AU - Fyodor Kondrashov ID - 882 IS - 16 JF - Human Molecular Genetics TI - Prediction of pathogenic mutations in mitochondrially encoded human tRNAs VL - 14 ER - TY - JOUR AB - Here, I describe a case of loss of the D-arm by mitochondrial cysteine tRNA in the nine-banded armadillo (Dasypus novemcinctus) convergent with mt tRNASer(AGY). Such evolution sheds light on the relationship between structure and function of tRNA molecules and its impact on the patterns of molecular evolution. AU - Kondrashov, Fyodor ID - 880 IS - 3 JF - Biofizika TI - The convergent evolution of the secondary structure of mitochondrial cysteine tRNA in the nine-banded armadillo Dasypus novemcinctus VL - 50 ER - TY - JOUR AB - Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G+C)-rich (or (A+T)-rich) genomes contain more (or fewer) amino acids encoded by (G+C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day. AU - Jordan, Ingo K AU - Fyodor Kondrashov AU - Adzhubeǐ, Ivan A AU - Wolf, Yuri I AU - Koonin, Eugene V AU - Kondrashov, Alexey S AU - Sunyaev, Shamil R ID - 893 IS - 7026 JF - Nature TI - A universal trend of amino acid gain and loss in protein evolution VL - 433 ER - TY - JOUR AB - Eukaryotic organisms have the remarkable ability to inherit states of gene activity without altering the underlying DNA sequence. This epigenetic inheritance can persist over thousands of years, providing an alternative to genetic mutations as a substrate for natural selection. Epigenetic inheritance might be propagated by differences in DNA methylation, post-translational histone modifications, and deposition of histone variants. Mounting evidence also indicates that small interfering RNA (siRNA)-mediated mechanisms play central roles in setting up and maintaining states of gene activity. Much of the epigenetic machinery of many organisms, including Arabidopsis, appears to be directed at silencing viruses and transposable elements, with epigenetic regulation of endogenous genes being mostly derived from such processes. AU - Zilberman, Daniel AU - Henikoff, Steven ID - 9529 IS - 5 JF - Current Opinion in Genetics and Development SN - 0959-437X TI - Epigenetic inheritance in Arabidopsis: Selective silence VL - 15 ER - TY - JOUR AB - Hydrogel stamps can microstructure solid surfaces, i.e., modify the surface topology of metals, glasses, and crystals. It is demonstrated that stamps soaked in an appropriate etchant can remove material with micrometer-scale precision. The Figure shows an array of concentric circles etched in glass using the immersion wet stamping process described (scale bar: 500 μm). AU - Smoukov, S. K. AU - Bishop, K. J. M. AU - Klajn, Rafal AU - Campbell, C. J. AU - Grzybowski, B. A. ID - 13431 IS - 11 JF - Advanced Materials KW - Mechanical Engineering KW - Mechanics of Materials KW - General Materials Science SN - 0935-9648 TI - Cutting into solids with micropatterned gels VL - 17 ER - TY - JOUR AB - Self-assembled monolayers (SAMs) of alkane thiols on gold and other metals are versatile constructs with which to study interfacial phenomena and reactions at surfaces. Surface properties of SAMs - e.g., wettability, stability in diverse environments, propensity to interact with or to resist adsorption of macromolecules -- depend on and can be controlled flexibly by the properties of the functional (head) groups in the w position of the alkyl chain. SAMs provide a basis for many important scientific and technological applications, ranging from micropatterning methods, through sensing, to biological recognition. Despite their importance, the literature on SAMs and the synthesis of molecules that constitute them remains scattered and often conflicting. The purpose of this Review is (i) to summarize the applications and physical properties of SAMs and (ii) to systematize the strategies of synthesis of ω-functionalized alkane thiols. Generic retrosynthetic scheme is developed that allows efficient synthetic planning. Issues related to the selection of appropriate protecting groups and the ways of introduction of the thiol functionality are discussed in detail, and illustrated with examples of syntheses of several complex alkane thiols. AU - Witt, Dariusz AU - Klajn, Rafal AU - Barski, Piotr AU - Grzybowski, Bartosz ID - 13433 IS - 18 JF - Current Organic Chemistry KW - Organic Chemistry SN - 1385-2728 TI - Applications, properties and synthesis of w-functionalized n-alkanethiols and disulfides - the building blocks of self-assembled monolayers VL - 8 ER - TY - JOUR AB - A new experimental technique is described that uses reaction−diffusion phenomena as a means of one-step microfabrication of complex, multilevel surface reliefs. Thin films of dry gelatin doped with potassium hexacyanoferrate are chemically micropatterned with a solution of silver nitrate delivered from an agarose stamp. Precipitation reaction between the two salts causes the surface to deform. The mechanism of surface deformation is shown to involve a sequence of reactions, diffusion, and gel swelling/contraction. This mechanism is established experimentally and provides a basis of a theoretical lattice-gas model that allows prediction surface topographies emerging from arbitrary geometries of the stamped features. The usefulness of the technique is demonstrated by using it to rapidly prepare two types of mold for passive microfluidic mixers. AU - Campbell, Christopher J. AU - Klajn, Rafal AU - Fialkowski, Marcin AU - Grzybowski, Bartosz A. ID - 13432 IS - 1 JF - Langmuir KW - Electrochemistry KW - Spectroscopy KW - Surfaces and Interfaces KW - Condensed Matter Physics KW - General Materials Science SN - 0743-7463 TI - One-step multilevel microfabrication by reaction−diffusion VL - 21 ER -