On the Ranks and Kernels Problem for Perfect Codes

A construction is proposed which, for n large enough, allows one to build perfect binary codes of length n and rank r, with kernel of dimension k, for any admissible pair (r, k) within the limits of known bounds.     

One-Step Chemical Synthesis of Native Met1-Linked Poly-Ubiquitin Chains

The enzyme-mediated construction of poly-ubiquitin (Ub) chains on target proteins leads to a variety of cellular responses and is involved in processes ranging from protein degradation to cell cycle control and immune responses. This complex post-translational modification system is under intense investigation, but generation of specific Ub chains and tools made thereof is not always trivial. We discovered that native methionine-1-linked polymeric ubiquitin chains can be constructed in a single chemical reaction. We validate correct folding and regioselective attachment of such chains using linkage specific proteases and further demonstrate that these poly-Ub chains can be converted into thioesters by the activating E1-enzyme. Subsequent ligation reactions using these in situ prepared thioesters leads to poly-ubiquitinated peptides.     

High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies

High‐fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids and induce lipotoxicity in various organs. Invitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in vivo; however, these approaches are not physiological as tissues are exposed to multiple fatty acids in vivo. Here we characterize circulating lipids in obesity‐prone rats fed an HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in vitro studies. Rats were fed an HFD (60 % kcal fat) or a control diet (10 % kcal fat) for 3 weeks; liver tissue and both portal and systemic blood were collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and phospholipids in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40 % lower in HFD‐fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n‐6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in vitro studies attempting to model lipid exposures that occur during in vivo HFD conditions.     

Development of Tyrphostin Analogues to Study Inhibition of the Mycobacterium tuberculosis Pup Proteasome System**

Tuberculosis is a global health problem caused by infection with the Mycobacterium tuberculosis (Mtb) bacteria. Although antibiotic treatment has dramatically reduced the impact of tuberculosis on the population, the existence and spreading of drug resistant strains urgently demands the development of new drugs that target Mtb in a different manner than currently used antibiotics. The prokaryotic ubiquitin-like protein (Pup) proteasome system is an attractive target for new drug development as it is unique to Mtb and related bacterial genera. Using a Pup-based fluorogenic substrate, we screened for inhibitors of Dop, the Mtb depupylating protease, and identified I-OMe-Tyrphostin AG538 ( 1 ) and Tyrphostin AG538 ( 2 ). The hits were validated and determined to be fast-reversible, non-ATP competitive inhibitors. We synthesized >25 analogs of 1 and 2 and show that several of the synthesized compounds also inhibit the depupylation actions of Dop on native substrate, FabD-Pup. Importantly, the pupylation activity of PafA, the sole Pup ligase in Mtb, was also inhibited by some of these compounds.     

Synthesis of Stable NAD+ Mimics as Inhibitors for the Legionella pneumophila Phosphoribosyl Ubiquitylating Enzyme SdeC

Stable NAD⁺ analogues carrying single atom substitutions in either the furanose ring or the nicotinamide part have proven their value as inhibitors for NAD⁺-consuming enzymes. To investigate the potential of such compounds to inhibit the adenosine diphosphate ribosyl (ADPr) transferase activity of the Legionella SdeC enzyme, we prepared three NAD⁺ analogues, namely carbanicotinamide adenosine dinucleotide (c-NAD⁺), thionicotinamide adenosine dinucleotide (S-NAD⁺) and benzamide adenosine dinucleotide (BAD). We optimized the chemical synthesis of thionicotinamide riboside and for the first time used an enzymatic approach to convert all three ribosides into the corresponding NAD⁺ mimics. We thus expanded the known scope of substrates for the NRK1/NMNAT1 enzyme combination by turning all three modified ribosides into NAD⁺ analogues in a scalable manner. We then compared the three NAD⁺ mimics side-by-side in a single assay for enzyme inhibition on Legionella effector enzyme SdeC. The class of SidE enzymes to which SdeC belongs was recently identified to be important in bacterial virulence, and we found SdeC to be inhibited by S-NAD⁺ and BAD with IC₅₀ values of 28 and 39 μM, respectively.     

Flicker noise conversion in CMOS LC oscillators: capacitance modulation dominance and core device sizing

This paper reports a low-voltage low-power injection-locked oscillator suitable for short range wireless transmitter applications in a wireless body area network (WBAN). Low-power transmitter with high efficiency is a major design challenge for short range wireless communication. Unlike conventional transmitters used for cellular communication, injection-locked transmitter shows reduced power consumption and high transmitter efficiency. The core block of an injection-locked transmitter is an injection-locked oscillator. In this work a low-voltage low-power injection-locked LC oscillator has been designed and fabricated employing self-cascode structure and body-terminal coupling. The proposed oscillator has been realized using 0.18-μm RF CMOS process. Experimental results indicate that the prototype oscillator can operate with a supply voltage as low as 0.9 V and consumes only 1.4 mW of power. The relatively low-voltage and low-power operation of the design makes it highly suitable for low-power transmitter applications.     

On partitions of an <Emphasis Type="Italic">n</Emphasis>-cube into nonequivalent perfect codes

We prove that for all n = 2^k ? 1, k ≥ 5, there exists a partition of the set of all binary vectors of length n into pairwise nonequivalent perfect binary codes of length n with distance 3.     

On the Structure of Symmetry Groups of Vasil’ev Codes

The structure of symmetry groups of Vasil’ev codes is studied. It is proved that the symmetry group of an arbitrary perfect binary non-full-rank Vasil’ev code of length n is always nontrivial; for codes of rank n − log(n + 1) +1, an attainable upper bound on the order of the symmetry group is obtained.__________Translated from Problemy Peredachi Informatsii, No. 2, 2005, pp. 42–49.Original Russian Text Copyright © 2005 by Avgustinovich, Solov’eva, Heden.Supported in part by the Royal Swedish Academy of Sciences.     

Electrochemical and morphological studies of an electroactive material derived from 3-hydroxyphenylacetic acid: a new matrix for oligonucleotide hybridization

This paper describes the formation of polymeric films derived from 3-hydroxyphenylacetic acid electropolymerized onto graphite electrodes through cyclic voltammetry. We observed the formation of an electroactive material over the electrode surface. The modified electrode showed significant blocking behavior to electron transfer reaction of the pair redox ferricyanide/ferrocyanide, indicating repulsion electrostatic with the negatively charged carboxylate groups of the polymer. The quasi-reversible behavior to Ru(NH₃)₆Cl₂ suggests electrostatic attraction, facilitating the charge transfer. The modified electrode was studied through electrochemical quartz crystal microbalance, electrochemical impedance spectroscopy, and atomic force microscopy. These analyses indicate modification of the graphite electrode. Surface analysis by AFM showed that the morphology of the modified electrode surface presents globular form, randomly distributed, and formed by lower globules with diameter near 100 nm. Immobilization and hybridization of oligonucleotide onto the modified electrode were successfully carried out by using both direct electrochemical oxidation of nitrogenated bases and the redox electroactive indicator methylene blue.     

In-Plate Chemical Synthesis of Isopeptide-Linked SUMOylated Peptide Fluorescence Polarization Reagents for High-Throughput Screening of SENP Preferences

Small ubiquitin-like modifiers (SUMOs) are conjugated to protein substrates in cells to regulate their function. The attachment of SUMO family members SUMO1-3 to substrate proteins is reversed by specific isopeptidases called SENPs (sentrin-specific protease). Whereas SENPs are SUMO-isoform or linkage type specific, comprehensive analysis is missing. Furthermore, the underlying mechanism of SENP linkage specificity remains unclear. We present a high-throughput synthesis of 83 isopeptide-linked SUMO-based fluorescence polarization reagents to study enzyme preferences. The assay reagents were synthesized via a native chemical ligation-desulfurization protocol between 11-mer peptides containing a γ-thiolysine and a SUMO3 thioester. Subsequently, five recombinantly expressed SENPs were screened using these assay reagents to reveal their deconjugation activity and substrate preferences. In general, we observed that SENP1 is the most active and nonselective SENP while SENP6 and SENP7 show the least activity. Furthermore, SENPs differentially process peptides derived from SUMO1-3, who form a minimalistic representation of diSUMO chains. To validate our findings, five distinct isopeptide-linked diSUMO chains were chemically synthesized and proteolysis was monitored using a gel-based read-out.