Stereoisomer composition of the chiral UV filter 4-methylbenzylidene camphor in environmental samples

4-Methylbenzylidene camphor (4-MBC) is an important organic UV filter used in many personal care products such as sunscreens and cosmetics. After use, 4-MBC may enter the aquatic environment due to its release from skin during recreational activities (swimming, bathing) and from personal hygiene measures (washing, laundering of cloths) via wastewater treatment plants (WWTPs). In fact, 4-MBC has been detected in wastewater, in surface waters, and even in fish. 4-MBC can exist as distinct cis-(Z)- and trans-(E)-isomers, both of which are chiral. Despite the fact that stereoisomers often show a different biological behavior, the stereochemistry of 4-MBC has hardly ever been considered in environmental or biological studies. In this study, enantioselective gas chromatography-mass spectrometry (GC-MS) was used to determine the stereoisomer composition of 4-MBC. For stereoisomer assignment, the pure enantiomers of (E)-4-MBC were synthesized from (+)- and (-)-camphor. The photochemical isomerization (sunlight) of these (E)-isomers to the corresponding (Z)-isomers eventually allowed the configurational assignment of all four stereoisomers of 4-MBC. In a technical material and in a major brand sun lotion, 4-MBC was shown to consist entirely (>99%) of (E)-isomers and to be racemic (R/S, 1.00 +/- 0.02). Wastewater showed the presence of both (E)- and (Z)-4-MBC with a clear excess of (E)-isomers (E > Z). Untreated wastewater showed a nearly racemic composition (R/S= 0.95-1.09), suggesting that most if not all commercial 4-MBC is racemic. Treated wastewater indicated some excess of (R)- or (S)-stereoisomers (R/S, 0.89-1.17), likely as a result of some enantioselective (bio)degradation in WWTPs. Residues of 4-MBC in lakes and in a river with inputs from WWTPs and/or recreational activities consisted mainly of (E)-4-MBC and, with exception of one lake (Greifensee), showed a small enantiomer excess (R/S, 1.04-1.16). In Greifensee, 4-MBC showed a higher enantiomer excess (R/S, 1.70-1.83), probably as a result of more extensive biotic degradation in this lake. The analysis of 4-MBC in a small number of fish from these lakes indicated residues with nearly racemic compositions or a moderate enantiomer excess (R/S, approximately 1.0-1.2) in roach (Rutilus rutilus), whereas in perch (Perca fluviatilis) a much higher enantiomer excess (R/S, approximately 5) was observed. The data indicate that the stereoisomer composition of 4-MBC in environmental samples is not only a function of initial product composition but is also modified by enantioselective processes in lakes and biota (fish).     

Substrate Scope for Human Histone Lysine Acetyltransferase KAT8

Biomedically important histone lysine acetyltransferase KAT8 catalyses the acetyl coenzyme A-dependent acetylation of lysine on histone and other proteins. Here, we explore the ability of human KAT8 to catalyse the acetylation of histone H4 peptides possessing lysine and its analogues at position 16 (H4K16). Our synthetic and enzymatic studies on chemically and structurally diverse lysine mimics demonstrate that KAT8 also has a capacity to acetylate selected lysine analogues that possess subtle changes on the side chain and main chain. Overall, this work highlights that KAT8 has a broader substrate scope beyond natural lysine, and contributes to the design of new chemical probes targeting KAT8 and other members of the histone lysine acetyltransferase (KAT) family.     

The evolution of MHC diversity by segmental duplication and transposition of retroelements

Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements, 14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically into two clades which were classified as "preduplication" and "postduplication" clades. Four Alu J elements that are shared by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a "preduplication" clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg) to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to the divergence of the New World primate from the human lineage (35-44 mya). Examination of the paralogous Alu integration sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within the Alu 3'-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended segmental duplication between 44 and 81 million years ago (mya), and that subsequent diversification of both genomic segments occurred because of the mobility and mutation of retroelements such as Alu repeats.     

Cloud computing-based parallel genetic algorithm for gene selection in cancer classification

Cancer classification is one of the main steps during patient healing process. This fact enforces modern clinical researchers to use advanced bioinformatics methods for cancer classification. Cancer classification is usually performed using gene expression data gained in microarray experiment and advanced machine learning methods. Microarray experiment generates huge amount of data, and its processing via machine learning methods represents a big challenge. In this study, two-step classification paradigm which merges genetic algorithm feature selection and machine learning classifiers is utilized. Genetic algorithm is built in MapReduce programming spirit which makes this algorithm highly scalable for Hadoop cluster. In order to improve the performance of the proposed algorithm, it is extended into a parallel algorithm which process on microarray data in distributed manner using the Hadoop MapReduce framework. In this paper, the algorithm was tested on eleven GEMS data sets (9 tumors, 11 tumors, 14 tumors, brain tumor 1, lung cancer, brain tumor 2, leukemia 1, DLBCL, leukemia 2, SRBCT, and prostate tumor) and its accuracy reached 100% for less than 25 selected features. The proposed cloud computing-based MapReduce parallel genetic algorithm performed well on gene expression data. In addition, the scalability of the suggested algorithm is unlimited because of underlying Hadoop MapReduce platform. The presented results indicate that the proposed method can be effectively implemented for real-world microarray data in the cloud environment. In addition, the Hadoop MapReduce framework demonstrates substantial decrease in the computation time.

     

Soundness and Completeness Proofs by Coinductive Methods

We show how codatatypes can be employed to produce compact, high-level proofs of key results in logic: the soundness and completeness of proof systems for variations of first-order logic. For the classical completeness result, we first establish an abstract property of possibly infinite derivation trees. The abstract proof can be instantiated for a wide range of Gentzen and tableau systems for various flavors of first-order logic. Soundness becomes interesting as soon as one allows infinite proofs of first-order formulas. This forms the subject of several cyclic proof systems for first-order logic augmented with inductive predicate definitions studied in the literature. All the discussed results are formalized using Isabelle/HOL’s recently introduced support for codatatypes and corecursion. The development illustrates some unique features of Isabelle/HOL’s new coinductive specification language such as nesting through non-free types and mixed recursion–corecursion.     

1053-nm-wavelength selection in a diode-laser-pumped Nd:YLF laser

We report on a Nd:YLF laser that operates at 1053 nm without optical intracavity elements for the suppression of the stronger 1047-nm transition. The Nd:YLF crystal is end pumped by a fiber optically coupled 10-W diode-laser bar. The different thermal-lensing focal lengths of the two main lasing wavelengths in a plane-parallel resonator were used to achieve the selection by tilting the end mirror slightly from its optimum position for maximum output power. With 9.8-W cw diode-laser-pumping power the 1053-nm Nd:YLF laser produces a maximum output power of 1.9 W in cw operation and nearly 1 W of average power at a Q-switch repetition rate of 15 kHz. The highest slope efficiency of 47% achieved in cw operation.     

Relational analysis of (co)inductive predicates, (co)algebraic datatypes, and (co)recursive functions

We present techniques for applying a finite relational model finder to logical specifications that involve high-level definitional principles such as (co)inductive predicates, (co)algebraic datatypes, and (co)recursive functions. In contrast to previous work, which focused on algebraic datatypes and restricted occurrences of unbounded quantifiers in formulas, we can handle arbitrary formulas by means of a three-valued Kleene logic. The techniques form the basis of the counterexample generator Nitpick for Isabelle/HOL. As case studies, we consider formulas about an inductively defined context-free grammar, a functional implementation of AA trees, and a coalgebraic list datatype.     

Extractive spectrophotometric method for determination of metribuzin herbicide and application of factorial design in optimization of various factors

A simple extractive spectrophotometric method has been described for the determination of metribuzin herbicide. Metribuzin was reacted with copper and a stable complex in the presence of ammonia (0.2M) at pH 10.5 was formed. The resulting yellow coloured complex was extracted in chloroform and showed absorption maxima at 340 nm. Beer's law was obeyed in the range of 0.8-25 microg mL(-1) with molar absorptivity of 5.67 x 10(3)L mol(-1)cm(-1). The composition of the complex was studied by Job's method of continuous variation and the results indicated that the mole ratio of metribuzin:Cu(2+) is 2:1. The optimum reaction conditions for complexation and other analytical parameters were evaluated. A two-level factorial design was also used to determine the effect of different parameters and their interaction on metribuzin:Cu(2+) complex formed. The method was successfully applied for the determination of metribuzin in commercial formulations and real samples.     

Saturation in neon- and nickel-like collisional soft-X-ray lasersat low pump energy

We report on the experimental demonstration of saturated X-ray laser output from collisionally pumped Ne-like Fe at 25.5 nm as well as Ni-like Ag and Pd at 14.0 nm and 14.7 nm, respectively, using a 100-ps drive pulse irradiation. A double-prepulse scheme and a 3-m radius-of-curvature target resulted in a gain-length product of gL=16.5 in the case of Fe, With a single prepulse and flat slab targets, gain-length products of 15.3 and 15.8 were obtained for Ag and Pd, respectively. Saturation was also confirmed by the observed reduction in beam divergence with increasing target length. The required drive energy used was only 30 J in a 100-ps pulse, corresponding to an irradiance of 12 TW/cm². A key role in the achievement of these results was played by the reduction in the roughness of the target surface in the case of the Pd X-ray laser     

Influence of Preheating Temperature on Microstructure Evolution and Hardness of High-Speed Steel AISI M50 Processed by Laser Powder Bed Fusion

The laser powder bed fusion (LPBF) technology has been involved in the tooling industry to produce tools with complex geometry and integrated functions. However, tool steels with high carbon content tend to crack due to the thermal stresses during the LPBF process. One solution is increasing the powder bed temperature to avoid large thermal gradients. In the present study, the influence of the preheating temperature on microstructure and corresponding hardness is systematically investigated. With the help of time–temperature–transformation diagram, the phase evolution during the LPBF process is systematically explained. AISI M50 samples are produced by LPBF from room temperature to a preheating temperature of 650 °C. Higher preheating temperatures shift the optimal laser parameter window to lower volume energy densities. A cellular/dendritic microstructure formed during the rapid solidification with retained austenite is located at the interdendritic regions. Moreover, a high preheating temperature reduces the retained austenite fraction, specifically from 39% without preheating to 7.6% at 650 °C preheating temperature.