Post-translational modifications (PTMs) broadly contribute to the recent explosion of proteomic data and possess a complexity surpassing that of protein design. PTMs are the chemical modification of a protein after its translation, and have wide effects broadening its range of functionality. Based on previous estimates, it is widely believed that more than half of proteins are glycoproteins. Whereas mutations can only occur once per position, different forms of post-translational modifications may occur in tandem. With the number and abundances of modifications constantly being discovered, there is no method to readily assess their relative levels. Here we report the relative abundances of each PTM found experimentally and putatively, from high-quality, manually curated, proteome-wide data, and show that at best, less than one-fifth of proteins are glycosylated. We make available to the academic community a continuously updated resource (http://selene.princeton.edu/PTMCuration) containing the statistics so scientists can assess “how many” of each PTM exists.

No abstract

During the last decade, the problem of production scheduling has been realized to be one of the most important problems in industrial plant operations especially when multipurpose/multiproduct batch processes are involved. This paper presents a novel mathematical formulation for the short-term scheduling of batch plants. The proposed formulation is based on a continuous time representation and results in a mixed integer linear programming (MILP) problem. The novel elements of the proposed formulation are (i) the decoupling of the task events from the unit events, (ii) the time sequencing constraints, and (iii) its linearity. In contrast to the previously presented continuous-time scheduling formulations, the proposed approach leads to smaller and simpler mathematical models which exhibit fewer binary and continuous variables, have smaller integrality gaps, require fewer constraints, need fewer linear programming relaxations, and can be solved in significantly less CPU time. Several examples are presented that illustrate the effectiveness of the proposed formulation, and comparisons with other approaches are provided.

An overview of developments in the scheduling of multiproduct/multipurpose batch and continuous processes is presented. Existing approaches are classified based on the time representation and important characteristics of chemical processes that pose challenges to the scheduling problem are discussed. In contrast to the discrete-time approaches, various continuous-time models have been proposed in the literature and their strengths and limitations are examined. Computational studies and applications are presented. The important issues of incorporating scheduling at the design stage and scheduling under uncertainty are also reviewed.

We present a novel method utilizing "saltless" pH gradient weak cation exchange-hydrophilic interaction liquid chromatography directly coupled to electron transfer dissociation (ETD) mass spectrometry for the automated on-line high throughput characterization of hypermodified combinatorial histone codes. This technique, performed on a low resolution mass spectrometer, displays an improvement over existing methods with an ϳ100-fold reduction in sample requirements and analysis time. The scheme presented is capable of identifying all of the major combinatorial histone codes present in a sample in a 2-h analysis. The large N-terminal histone peptides are eluted by the pH and organic solvent weak cation exchangehydrophilic interaction liquid chromatography gradient and directly introduced via nanoelectrospray ionization into a benchtop linear quadrupole ion trap mass spectrometer equipped with ETD. Each polypeptide is sequenced, and the modification sites are identified by ETD fragmentation. The isobaric trimethyl and acetyl modifications are resolved chromatographically and confidently distinguished by the synthesis of mass spectrometric and chromatographic information. We demonstrate the utility of the method by complete characterization of human histone H3.2 and histone H4 from butyrate-treated cells, but it is generally applicable to the analysis of highly modified peptides. We find this methodology very useful for chromatographic separation of isomeric species that cannot be separated well by any other chromatographic means, leading to less complicated tandem mass spectra. The improved separation and increased sensitivity generated novel information about much less abundant forms. In this method demonstration we report over 200 H3. Eukaryotic nuclear DNA is nominally compacted into chromatin fibers by use of nucleosomes consisting of a 146-bp section of DNA wrapped around a core of histone proteins (1). Dynamic post-translational modifications (PTMs) 1 of the histones, primarily in the accessible N-terminal region or histone "tail," are an important but not fully understood component of dynamic gene regulation, epigenetic inheritance of cellular memory, genomic stability, and other nuclear mechanisms (2-7). An overwhelming number of studies point to the existence of a histone code of biological logic written on these proteins through these PTMs that are read by a diverse array of "effector" proteins leading to distinct biological events (3). Many single PTM sites on various histone proteins have been decidedly linked to specific physiological processes, such as histone H3 Lys-9 trimethylation (H3K9me3), which is associated with heterochromatin formation (one mode of gene silencing). Nevertheless what effect multiple modifications occurring in combination may have on modulating the histone code signal remains to be determined. Significant progress has been made toward understanding histone modifications using antibody-based histone modification detection methods and by bottom up mass spectrometry (4 -6). However...