Analysis of ergonomics problems contact-centers

The analysis of the ergonomic problems of the contact center. It allocates main factors of influence on man- operator

Simple Chemical Transformation of Lignocellulosic Biomass into Furans for Fuels and Chemicals

Lignocellulosic biomass is a plentiful and renewable resource for fuels and chemicals. Despite this potential, nearly all renewable fuels and chemicals are now produced from edible resources, such as starch, sugars, and oils; the challenges imposed by notoriously recalcitrant and heterogeneous lignocellulosic feedstocks have made their production from nonfood biomass inefficient and uneconomical. Here, we report that <i>N</i>,<i>N</i>-dimethylacetamide (DMA) containing lithium chloride (LiCl) is a privileged solvent that enables the synthesis of the renewable platform chemical 5-hydroxymethylfurfural (HMF) in a single step and unprecedented yield from untreated lignocellulosic biomass, as well as from purified cellulose, glucose, and fructose. The conversion of cellulose into HMF is unabated by the presence of other biomass components, such as lignin and protein. Mechanistic analyses reveal that loosely ion-paired halide ions in DMA−LiCl are critical for the remarkable rapidity (1−5 h) and yield (up to 92%) of this low-temperature (≤140 °C) process. The simplicity of this chemical transformation of lignocellulose contrasts markedly with the complexity of extant bioprocesses and provides a new paradigm for the use of biomass as a raw material for a renewable energy and chemical industries

Conversion of Azides into Diazo Compounds in Water

Diazo compounds are in widespread use in synthetic organic chemistry but have untapped potential in chemical biology. We report on the design and optimization of a phosphinoester that mediates the efficient conversion of azides into diazo compounds in phosphate buffer at neutral pH and room temperature. High yields are maintained in the presence of common nucleophilic or electrophilic functional groups, and reaction progress can be monitored by colorimetry. As azido groups are easy to install and maintain in biopolymers or their ligands, this new mode of azide reactivity could have substantial utility in chemical biology

Residues Lys-6 to Arg-14 of PTEN and the canonical PIP₂-binding motif.

<p>Each conserved residue in this motif is altered in cancer according to the COSMIC database.</p

Initial characterization of PTEN.

<p>(A) Analysis of PTEN-L, wild-type PTEN, and K13A PTEN on a Coomassie R-250–stained polyacrylamide (12% w/v) gel containing sodium dodecylsulfate (0.1% w/v). (B) Representative progress curves for the turnover of PIP₃ (10, 15, or 40 μM) by wild-type PTEN. Reactions were performed in 50 mM Tris–HCl buffer, pH 7.6, containing EDTA (2.0 mM), MESG (0.20 mM), DTBA (40 mM), and NaCl (0, 100, or 200 mM), and were initiated with the addition of PTEN to 20 nM. Absorbance at 360 nM was converted to concentration by using Δ<i>ε</i> = 11 mM⁻¹cm⁻¹. </p

Conformational Stability and Catalytic Activity of PTEN Variants Linked to Cancers and Autism Spectrum Disorders

Phosphoinositides are membrane components that play critical regulatory roles in mammalian cells. The enzyme PTEN, which catalyzes the dephosphorylation of the phosphoinositide PIP₃, is damaged in most sporadic tumors. Mutations in the <i>PTEN</i> gene have also been linked to autism spectrum disorders and other forms of delayed development. Here, human PTEN is shown to be on the cusp of unfolding under physiological conditions. Variants of human PTEN linked to somatic cancers and disorders on the autism spectrum are shown to be impaired in their conformational stability, catalytic activity, or both. Those variants linked only to autism have activity higher than the activity of those linked to cancers. PTEN-L, which is a secreted <i>trans</i>-active isoform, has conformational stability greater than that of the wild-type enzyme. These data indicate that PTEN is a fragile enzyme cast in a crucial role in cellular metabolism and suggest that PTEN-L is a repository for a critical catalytic activity

A Key <i>n</i>→π* Interaction in <i>N</i>‑Acyl Homoserine Lactones

Many Gram-negative bacteria employ <i>N</i>-acyl homoserine lactones (AHLs) as signal molecules for quorum sensing. The binding of AHLs to their target LuxR-type receptor proteins can effect changes in growth, virulence, and other phenotypes. LuxR-type receptors therefore present attractive pharmaceutical targets for control of bacterial pathogenesis. Here, we present X-ray crystallographic and computational evidence that the conformation of free AHLs is biased away from the conformation observed when bound to their cognate receptor due to the influence of an <i>n</i>→π* interaction. In this <i>n</i>→π* interaction, the <i>p</i>-type lone pair (<i>n</i>) of the <i>N</i>-acyl oxygen overlaps with the π* orbital of the lactone carbonyl group. This overlap results in the release of approximately 0.64 kcal/mol of energy. We also show that this interaction can be attenuated by installing electron-withdrawing groups on the <i>N</i>-acyl chain. Modulating this previously unappreciated interaction could present a new avenue toward effective inhibitors of bacterial quorum sensing

Human Collagen Prolyl 4‑Hydroxylase Is Activated by Ligands for Its Iron Center

Collagen is the most abundant protein in animals. The posttranslational hydroxylation of proline residues in collagen contributes greatly to its conformational stability. Deficient hydroxylation is associated with a variety of disease states, including scurvy. The hydroxylation of proline residues in collagen is catalyzed by an Fe­(II)- and α-ketoglutarate-dependent dioxygenase, collagen prolyl 4-hydroxylase (CP4H). CP4H has long been known to suffer oxidative inactivation during catalysis, and the cofactor ascorbate (vitamin C) is required to reactivate the enzyme by reducing its iron center from Fe­(III) to Fe­(II). Herein, we report on the discovery of the first synthetic activators of CP4H. Specifically, we find that 2,2′-bipyridine-4-carboxylate and 2,2′-bipyridine-5-carboxylate serve as ligands for the iron center in human CP4H that enhance the rate of ascorbate-dependent reactivation. This new mode of CP4H activation is available to other biheteroaryl compounds but does not necessarily extend to other prolyl 4-hydroxylases. As collagen is weakened in many indications, analogous activators of CP4H could have therapeutic benefits

Notional schemes and diagrams for catalysis by K13A PTEN, wild-type PTEN, and PTEN-L.

<p>(A) The binding motif for PIP₂ (P) is absent in K13A PTEN. As a result, the K13A variant remains in its tense (T) state for all substrate concentrations at any salt concentration. (B) Wild-type PTEN has complex kinetic behavior. Low salt concentration favors the binding of PIP₂. The wild-type enzyme is in its relaxed (R) state and exhibits Michaelis–Menten kinetics. Increasing salt concentration leads to decreasing affinity for PIP₂ and a greater fraction of the enzyme being in the T state. As more PIP₃ (S) is hydrolyzed, the increasing concentration of P leads to a greater fraction of the enzyme being in the R state. (C) PTEN-L is in the R state at any salt concentration and is unaffected by P.</p

Optimized Diazo Scaffold for Protein Esterification

The <i>O</i>-alkylation of carboxylic acids with diazo compounds provides a means to esterify carboxylic acids in aqueous solution. A Hammett analysis of the reactivity of diazo compounds derived from phenylglycinamide revealed that the (<i>p</i>-methylphenyl)­glycinamide scaffold has an especially high reaction rate and ester/alcohol product ratio and esterifies protein carboxyl groups more efficiently than any known reagent