Building a biological space based on protein sequence similarities and biological ontologies

Assignment of function to protein sequence is a task of growing importance in the life sciences, as new high-throughput sequencing DNA technologies generate ever increasing quantities of genomic and meta-genomic data. Patterns within the sequence space, caused by the evolutionary conservation and assembly of protein domains, make possible the inference of function from sequence similarity. Clustering similar sequences is a useful technique for finding conserved sequences; the CluSTr database is a publicly-available database arranging proteins in a hierarchy structured by similarity. The protein classification tool InterProScan builds on this approach by applying a range of methods to detect proteins that contain signatures indicative of the presence of particular conserved domains. The use of ontologies to describe protein function provides a flexible and abstract language to classify proteins. Together, these techniques can provide an understanding of the shape of the protein space, and can be used to explore the unchartered waters of the emerging metagenomic world.     

Dual Redox and Thermoresponsive Double Hydrophilic Block Copolymers with Tunable Thermoresponsive Properties and Self‐Assembly Behavior

The synthesis, tunable thermoresponsive properties, and self‐assembly of dual redox and thermoresponsive double hydrophilic block copolymers having pendant disulfide linkages (DHBCss) are reported. Well‐defined DHBCss composed of a hydrophilic poly(ethylene oxide) block and a dual thermo‐ and reduction‐responsive random copolymer block containing pendant disulfide linkages are synthesized by atom transfer radical polymerization. Their lower critical solution temperature (LCST) transitions are adjusted through modulating pendant hydrophobic–hydrophilic balance with disulfide–thiol–sulfide chemistry. Further, these DHBCss derivatives are converted to disulfide‐crosslinked nanogels at temperatures above LCST through temperature‐driven self‐assembly and in situ disulfide crosslinking. They exhibit enhanced colloidal stability and further reduction‐responsive degradability, thus demonstrating versatility of dual thermo‐ and reduction‐responsive smart materials.

     

Distal Weak Coordination of Acetamides in Ruthenium(II)‐Catalyzed C−H Activation Processes

C?H activations with challenging arylacetamides were accomplished by versatile ruthenium(II) biscarboxylate catalysis. The distal C?H functionalization offers ample scope—including twofold oxidative C?H functionalizations and alkyne hydroarylations—through facile base‐assisted internal electrophilic‐type substitution (BIES) C?H ruthenation by weak O‐coordination.     

Electrooxidative Ruthenium‐Catalyzed C−H/O−H Annulation by Weak O‐Coordination

Electrocatalysis has been identified as a powerful strategy for organometallic catalysis, and yet electrocatalytic C?H activation is restricted to strongly N‐coordinating directing groups. The first example of electrocatalytic C?H activation by weak O‐coordination is presented, in which a versatile ruthenium(II) carboxylate catalyst enables electrooxidative C?H/O?H functionalization for alkyne annulations in the absence of metal oxidants; thereby exploiting sustainable electricity as the sole oxidant. Mechanistic insights provide strong support for a facile organometallic C?H ruthenation and an effective electrochemical reoxidation of the key ruthenium(0) intermediate.     

Electrooxidative Rhodium‐Catalyzed C−H/C−H Activation: Electricity as Oxidant for Cross‐Dehydrogenative Alkenylation

Rhodium(III) catalysis has enabled a plethora of oxidative C?H functionalizations, which predominantly employ stoichiometric amounts of toxic and/or expensive metal oxidants. In contrast, we herein describe the first electrochemical rhodium‐catalyzed C?H activation that avoids hazardous chemical oxidants. Environmentally benign twofold C?H/C?H functionalizations were accomplished with weakly coordinating benzoic acids and benzamides, employing electricity as the terminal oxidant and generating H₂ as the sole byproduct.     

Micellar Catalysis for Ruthenium(II)‐Catalyzed C−H Arylation: Weak‐Coordination‐Enabled C−H Activation in H2O

Chemoselective C?H arylations were accomplished through micellar catalysis by a versatile single‐component ruthenium catalyst. The strategy provided expedient access to C?H‐arylated ferrocenes with wide functional‐group tolerance and ample scope through weak chelation assistance. The sustainability of the C?H arylation was demonstrated by outstanding atom‐economy and recycling studies. Detailed computational studies provided support for a facile C?H activation through thioketone assistance.     

Reactions of 1,1-bis(dimethylamino)-1,3-butadiene with olefins – (4 + 2) cycloadditions and zwitterion formation

1,1-Bis(dimethylamino)-1,3-butadiene ( 1 ) as a strong donor diene (E_1/2 = 0.03 V vs. SCE, 1st IP_v = 6.94 eV) is treated with acrylonitrile, dimethyl dicyanofumarate, and tetracyanoethylene. Cycloaddition with acrylonitrile is slow and requires elevated temperatures at which elimination of dimethylamine with formation of 1-cyano-2-(dimethylamino)-1,3-cyclohexadiene occurs. The reaction of 1 with TCNE at −40°C in acetonitrile is very fast and leads to the zwitterion 5 . At T ⩾ −20°C, 5 eliminates hydrogen cyanide to give a highly colored (λ_max = 489 nm, lgϵ = 4.716) merocyanine. A zwitterion 9 generated from 1 and dimethyl dicyanofumarate can be isolated in crystalline form. The structural analysis shows that the zwitterions are produced by attack of the olefin at the antiperiplanar conformation of 1 . Both zwitterions which can be trapped as crystalline picrates cannot be converted to cycloadducts. These results suggest that cycloaddition is observed if zwitterion formation becomes energetically unfavorable.     

Nonstandard characterization of convergence in law for -valued random variables

We prove for random variables with values in the space of cadlag functions - endowed with the supremum metric - that convergence in law is equivalent to nonstandard constructions of internal -cadlag processes, which represent up to an infinitesimal error the limit process. It is not required that the limit process is concentrated on the space , so that the theory is applicable to a wider class of limit processes as e.g. to Poisson processes or Gaussian processes. If we consider in the Skorokhod metric - instead of the supremum metric - we obtain a corresponding equivalence to constructions of internal processes with -separated jumps. We apply these results to functional central limit theorems.

     

Asymptotic expansions in the conditional central limit theorem

Let X_n, n , be i.i.d. with mean 0, variance 1, and E(¦X_n¦^r) < ∞ for some r 3. Assume that Cramér's condition is fulfilled. We prove that the conditional probabilities P(1/√n Σ_{i = 1}ⁿ X_i t¦B) can be approximated by a modified Edgeworth expansion up to order o(1/n^{(r − 2)/2)}), if the distances of the set B from the σ-fields σ(X₁, …, X_n) are of order O(1/n^{(r − 2)/2)}(lg n)^β), where β < −(r − 2)/2 for r and β < −r/2 for r . An example shows that if we replace β < −(r − 2)/2 by β = −(r − 2)/2 for r (β < −r/2 by β = −r/2 for r ) we can only obtain the approximation order O(1/n^{(r − 2)/2)}) for r (O(lg lgn/n^{(r − 2)/2)}) for r ).