bluuebunny/crossref_metadata_2025 huggingface dataset:
Ensemble Models
Authors: Fuentes Montserrat , Foley Kristen
Published: December 2014

An ensemble, or sample, of competing numerical models has been used in many applications to represent different predictions of the true state of a physical system. Ensembles of computer models (e.g. weather, climate, air quality, ocean models) are often used to forecast future states of a physical system and to quantify uncertainty in the numerical model predictions. Various statistical methods have been proposed to improve ensemble predictions from deterministic computer simulations based on actual measurements of the physical systems (e.g. data assimilation, Bayesian model averaging). Ensemble data mining methods have also been developed for a wide variety of applications to combine different versions of a statistical model (e.g. time series models, simple regression models, neural networks) to improve the predictive model performance. We present different statistical criteria that have been proposed to select or weight ensemble members for both numerical model‐based and statistical model‐based ensembles.
Extremes for Processes in Random Environments
Authors: Piterbarg Vladimir I.
Published: December 2014

We give definitions for random processes in random environment, in particular, Gaussian random processes in random environment, or, in other words, conditionally Gaussian processes. With some constrains on a random environment, we formulate the large deviation principle for Gaussian processes in the random environment. Further, we consider a class of Gaussian processes in random environment that allows exact calculations for probabilities of large extremes. This is a class of Gaussian stationary processes with smooth bounded random stationary variance. We show how the random environment affects on such probabilities.
Extremes: Spatial Models and Prediction
Authors: Stoev Stilian A.
Published: December 2014

Max‐stable processes and fields are reviewed as natural models of spatial extremes. Their stochastic properties, extremal integral, and de Haan spectral representations are briefly discussed. A solution to the prediction problem for a large class of spectrally discrete max‐linear models is presented and illustrated over a data set of rainfall extremes.
Extremes: Spatial Nonstationary Statistical Modeling
Authors: Peng Liang , Zhang Zhengjun
Published: December 2014

Data in environmental studies often appear to be both spatially correlated and nonstationary. Recent extreme events in climate call for more advanced statistical models and inference procedures to deal with spatial extremes. We review some methodologies proposed in the literature and discuss some challenging theoretical and practical questions.
Fractal Dimensions
Authors: Li Bai‐Lian
Published: December 2014

The term ‘fractal’ (from the Latinfractus, meaning ‘broken’), introduced by Benoit Mandelbrot about 25 years ago, is used to characterize spatial and/or temporal phenomena that are continuous but not differentiable. Geometrically, a fractal is a rough or fragmented geometric shape that can be subdivided in parts, each of which is (at least approximately) a reduced‐size copy of the whole. Fractal structures do not have a single length scale, while fractal processes (e.g. time series) cannot be characterized by a single time scale. Fractal theory offers methods for describing the inherent irregularity of natural objects. In fractal analysis, the Euclidean concept of ‘length’ is viewed as a process. This process is characterized by a constant parameterDknown as the fractal (or fractional) dimension. There are many fractal dimensions introduced in mathematical and physical literature. Fractal dimensions can be positive, negative, complex, fuzzy, multifractal, etc. The two most commonly used are the Hausdorf dimension and capacity.
Gaussian Process: Theory
Authors: Davis Richard A.
Published: December 2014

The class of Gaussian processes is one of the most widely used families of stochastic processes for modeling dependent data observed over time, or space, or time and space. The popularity of such processes stems primarily from two essential properties. First, a Gaussian process is completely determined by its mean and covariance functions. This property facilitates model fitting as only the first‐ and second‐order moments of the process require specification. Second, solving the prediction problem is relatively straightforward. The best predictor of a Gaussian process at an unobserved location is a linear function of the
observed
values and, in many cases, these functions can be computed rather quickly using recursive formulas.
J
oint
M
odels
Authors: S. Thompson Darby J.
Published: December 2014

Joint modeling encompasses strategies to simultaneously model several outcomes of interest. There are three principal strategies; classical joint modeling, conditional models, and conditional independence models. Likely the most pervasive area of joint modeling is in the modeling of longitudinal and time‐to‐event data; in particular, accounting for drop‐out in longitudinal data or incorporating error‐prone, sporadically measured, longitudinal outcomes in models for event times. Conditional independence is a popular strategy, which assumes the outcomes of interest are noisy, independent measures of some underlying latent process; it is this process that induces their correlation providing a tractable assumption in many practical settings.
Markov Process, Hidden
Authors: Zucchini Walter , Macdonald Iain L.
Published: December 2014

Hidden Markov processes, more commonly known as hidden Markov models (HMMs), are a class of models for time series {

X
t

,
t
 = 0, 1, 2, …} in which the probability distribution of

X
t

is determined by the unobserved (‘hidden’) state

C
t

of an
m
‐state Markov chain {

C
t

,
t
 = 0, 1, 2, …}.
Massive Data, Models for
Authors: Zhang Hao
Published: December 2014

Massive data present a challenge to the use and manipulation of well‐studied inferential strategies such as maximum likelihood estimation, Bayesian methods, and best linear prediction (kriging) since these methods require the inversion of a large covariance matrix. This entry introduces statistical models that circumvent computational issues, which include local models, covariance tapering, low‐rank models, and Markovian models.
Matrix Population Models
Authors: Caswell Hal
Published: December 2014

Matrix population models are discrete‐time structured population models in which individuals are classified into discrete stages (age classes, size classes, developmental stages, spatial locations, etc.).
Max‐Stable Processes
Authors: Padoan Simone A.
Published: December 2014

Environmental problems such as floods require statistical analysis that takes into account the complex nature of the data, namely, the observations that are sampled at different spatial points in a given region for a certain time. Thus the spatial dependence structure cannot be ignored. Extreme statistics for the design of structures for flood protection, for the study of the structural failures such as those in bridges, dams, and so on, for the prediction of heat waves, and other spatial extremes should be based on a solid theoretical framework. Max‐stable processes provide such a theory and in the last decade have emerged as fertile ground for research and have become a common tool for the statistical modeling of spatial extremes. This article provides a summary of max‐stable processes.
Point Processes, Temporal
Authors: Brillinger David R. , Guttorp Peter M. , Schoenberg Frederic Paik
Published: December 2014

A temporal point process is a random process whose realizations consist of the times {τ

j

}, τ

j

 ∈ ℝ,
j
 = 0, ±1, ±2, … of isolated events scattered in time. A point process is also known as a counting process or a random scatter. The times may correspond to events of several types.
Seismological Modeling
Authors: Rathbun Stephen L.
Published: December 2014

Temporal point process models for seismological applications are described including Poisson point process, Hawkes' self‐exciting point process for clustered events, and the stress‐release point process for regularly‐spaced events. Earthquake magnitudes may be included in marked versions of the point process models. In seismology, the self‐exciting point process model is often referred to as the epidemic‐type aftershock sequences (ETAS) model and is suitable for modeling aftershock sequences. Dependencies among seismological events may be described using Laguerre polynomials or the modified Omori function and versions of the model can be constructed under which high‐magnitude shocks produce a higher mean number of aftershocks. The ETAS model can also accommodate long‐term trends and periodic behavior. Under the stress‐release model describes the release of tectonic stress following each earthquake. Maximum likelihood estimation of model parameters and its statistical inference are briefly described. Methods are applied to a sequence of 432 California earthquakes.
Stochasticity
Authors: Cox D.R.
Published: December 2014

Stochasticity is the abstract noun associated with the adjective
stochastic
, which in its modern usage means
random
, with nuances that if represented mathematically, probability is the appropriate language and moreover, often, that there is a dynamic element involved.
B
rownian Motion
Authors: Riedi Rudolf H.
Published: December 2014

This article on Brownian motion starts with a short historical survey on its discovery and importance and continues with its most relevant properties. Mathematically detailed formulas are given and connections between the properties are indicated, however no derivations or proofs are provided.

The properties covered start with the mathematical modeling of Brownian motion via the Wiener process; equivalent definitions and constructions such as the Lévy characterization, the midpoint displacement, and the rescaled random walks are discussed. Basic properties given include uniqueness, symmetry, restarted Brownian motion, and time inversion. More advanced topics treated cover stopping times, the strong Markov property, the reflection principle, extreme values, escape times from a strip, and last visits. Path oscillations, stationarity, Gaussian white noise, and Karhunen‐Löwe expansions are also discussed. Brownian motion with drift, the Brownian bridge, as well as intersections, recurrence, and transience of Brownian motion in higher dimensions, are mentioned briefly.
Copulas and Copula Models
Authors: Genest Christian , Nešlehová Johanna
Published: December 2014

This entry introduces the notion of copula, reviews classical copula models, and describes their main properties. The entry also presents rank‐based estimation procedures and goodness‐of‐fit tests for copula modeling.
Elliptical Symmetry
Authors: Paindaveine Davy
Published: December 2014

This article first reviews the definition of elliptically symmetric distributions and discusses identifiability issues. It then presents results related to the corresponding characteristic functions, moments, marginal and conditional distributions, and considers the absolutely continuous case. Some well‐known instances of elliptical distributions are provided. Finally, inference in elliptical families is briefly discussed.
One‐Pot Synthesis of 2‐Arylquinazolines and Tetracyclic Isoindolo[1,2‐a]quinazolines via Cyanation Followed by Rearrangement of ortho‐Substituted 2‐Halo‐N‐arylbenzamides
Authors: Gawande Sachin D. , Zanwar Manoj R. , Kavala Veerababurao , Kuo Chun‐Wei , Rajawinslin R. R. , Yao Ching‐Fa
Published: December 2014

The one‐pot synthesis of substituted 2‐arylquinazoline derivatives and tetracylic isoindolo[1,2‐a]quinazoline via cyanation followed by rearrangement of ortho‐substituted 2‐halo‐N‐arylbenzamides is described. Using dimethyl sulfoxide (DMSO) as the solvent, the cleavage of the tetracyclic isoindole fused quinazoline leads to the formation of 2‐arylquinazoline derivatives. When 1,4‐dioxane is used as the solvent, tetracyclic isoindole fused quinazolines are produced in good yield. A wide range of products, including 2‐phenylquinazolin‐4‐amine, 4‐methyl‐2‐phenylquinazoline and long‐chain 2‐phenyl‐4‐styrylquinazoline derivatives were produced in moderate to good yields using DMSO as the solvent. However, various tetracyclic isoindole fused quinazoline derivatives were obtained in good yields when 1,4‐dioxane was used as the solvent.

magnified image
Peptide o‐Aminoanilides as Crypto‐Thioesters for Protein Chemical Synthesis
Authors: Wang Jia‐Xing , Fang Ge‐Min , He Yao , Qu Da‐Liang , Yu Min , Hong Zhang‐Yong , Liu Lei
Published: December 2014

Fully unprotected peptide o‐aminoanilides can be efficiently activated by NaNO2 in aqueous solution to furnish peptide thioesters for use in native chemical ligation. This finding enables the convergent synthesis of proteins from readily synthesizable peptide o‐aminoanilides as a new type of crypto‐thioesters. The practicality of this approach is shown by the synthesis of histone H2B from five peptide segments. Purification or solubilization tags, which are sometimes needed to improve the efficiency of protein chemical synthesis, can be incorporated into the o‐aminoanilide moiety, as demonstrated in the preparation of the cyclic protein lactocyclicin Q.
Sequential Synthesis of Coordination Polymersomes
Authors: Ohtani Ryo , Inukai Munehiro , Hijikata Yuh , Ogawa Tetsuya , Takenaka Mikihito , Ohba Masaaki , Kitagawa Susumu
Published: December 2014

Novel organic–inorganic hybrid liposomes, so‐called coordination polymersomes (CPsomes), with artificial domains that exhibit strong lateral cohesion were prepared by a three‐step procedure that formed a coordinative interaction leading to a lipid bilayer. First, the lipophilic complex (dabco‐C18)[Mn(N)(CN)4(dabco‐C18)] (1; dabco‐C18+=1,4‐diazabicyclo[2,2,2]octane‐(CH2)17CH3 cation), was synthesized. 1 has a lipophilic alkyl tail part and a tetracyanometallate head group, which can be used for an expansion to two‐dimensional coordination networks. Second, 1 and 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine were mixed to prepare the liposomes. Finally, CPsomes were obtained by the addition of transition‐metal ions (M) to form unilamellar faceted liposomes with plain CP raft domains with MnCNM linkages. The concentration of 1 influences the size of the CP raft domains and the shape of the CPsomes. The synthesis of coordination polymers in lipid bilayers is a novel approach for the construction of artificial architectures as raft domains, for example, in cell membranes.
A Sharp Thermal Transition of Fast Aromatic‐Ring Dynamics in Ubiquitin
Authors: Kasinath Vignesh , Fu Yinan , Sharp Kim A. , Wand A. Joshua
Published: December 2014

Aromatic amino acid side chains have a rich role within proteins and are often central to their structure and function. Suitable isotopic‐labelling strategies enable studies of sub‐nanosecond aromatic‐ring dynamics using solution NMR relaxation methods. Surprisingly, it was found that the three aromatic side chains in human ubiquitin show a sharp thermal dynamical transition at approximately 312 K. Hydrostatic pressure has little effect on the low‐temperature behavior, but somewhat decreases the amplitude of motion in the high‐temperature regime. Therefore, below the transition temperature, ring motion is largely librational. Above this temperature, a complete ring‐rotation process that is fully consistent with a continuous diffusion not requiring the transient creation of a large activated free volume occurs. Molecular dynamics simulations qualitatively corroborate this view and reinforce the notion that the dynamical character of the protein interior has much more liquid‐alkane‐like properties than previously appreciated.
Integrative Chemical Biology Approaches for Identification and Characterization of “Erasers” for Fatty‐Acid‐Acylated Lysine Residues within Proteins
Authors: Liu Zheng , Yang Tangpo , Li Xin , Peng Tao , Hang Howard C. , Li Xiang David
Published: December 2014

Acylation of proteins with fatty acids is important for the regulation of membrane association, trafficking, subcellular localization, and activity of many cellular proteins. While significant progress has been made in our understanding of the two major forms of protein acylation with fatty acids, N‐myristoylation and S‐palmitoylation, studies of the acylation of lysine residues, within proteins, with fatty acids have lagged behind. Demonstrated here is the use of integrative chemical biology approaches to examine human sirtuins as de‐fatty‐acid acylases in vitro and in cells. Photo‐crosslinking chemistry is used to investigate enzymes which recognize fatty‐acid acylated lysine. Human Sirt2 was identified as a robust lysine de‐fatty‐acid acylase in vitro. The results also show that Sirt2 can regulate the acylation of lysine residues, of proteins, with fatty acids within cells.
Photochromic Metal–Organic Frameworks: Reversible Control of Singlet Oxygen Generation
Authors: Park Jihye , Feng Dawei , Yuan Shuai , Zhou Hong‐Cai
Published: December 2014

The controlled generation of singlet oxygen is of great interest owing to its potential applications including industrial wastewater treatment, photochemistry, and photodynamic therapy. Two photochromic metal–organic frameworks, PC‐PCN and SO‐PCN, have been developed. A photochromic reaction has been successfully realized in PC‐PCN while maintaining its single crystallinity. In particular, as a solid‐state material which inherently integrates the photochromic switch and photosensitizer, SO‐PCN has demonstrated reversible control of 1O2 generation. Additionally, SO‐PCN shows catalytic activity towards photooxidation of 1,5‐dihydroxynaphthalene.
Unified Total Syntheses of (−)‐Medicarpin, (−)‐Sophoracarpan A, and (±)‐Kushecarpin A with Some Structural Revisions
Authors: Feng Zhen‐Gao , Bai Wen‐Ju , Pettus Thomas R. R.
Published: December 2014

The total syntheses of medicarpin, sophoracarpan A, and kushecarpin A from a common intermediate are achieved by using ortho‐ and para‐quinone methide chemistry. Additionally, the relative stereochemistry of sophoracarpan A and B have been reassigned.
Long‐Lived Engineering of Glycans to Direct Stem Cell Fate
Authors: Pulsipher Abigail , Griffin Matthew E. , Stone Shannon E. , Hsieh‐Wilson Linda C.
Published: December 2014

Glycans mediate many critical, long‐term biological processes, such as stem cell differentiation. However, few methods are available for the sustained remodeling of cells with specific glycan structures. A new strategy that enables the long‐lived presentation of defined glycosaminoglycans on cell surfaces using HaloTag proteins (HTPs) as anchors is reported. By controlling the sulfation patterns of heparan sulfate (HS) on pluripotent embryonic stem cell (ESC) membranes, it is demonstrated that specific glycans cause ESCs to undergo accelerated exit from self‐renewal and differentiation into neuronal cell types. Thus, the stable display of glycans on HTP scaffolds provides a powerful, versatile means to direct key signaling events and biological outcomes such as stem cell fate.
A Heterobimetallic Superoxide Complex formed through O2 Activation between Chromium(II) and a Lithium Cation
Authors: Schax Fabian , Suhr Simon , Bill Eckhard , Braun Beatrice , Herwig Christian , Limberg Christian
Published: December 2014

The reaction of 1,1,3,3‐tetraphenyl‐1,3‐disiloxandiol (LH2) with n‐butyllithium and CrCl2 results in a mononuclear chromium(II) complex (1) that further reacts with O2 at low temperatures to yield a mononuclear chromium(III) superoxide complex [L2CrO2(THF)][Li2(THF)3] (2). The crystal structure revealed that the chromium superoxido entity is stabilized by the coordination to an adjacent lithium cation. Complex 2 thus contains an unprecedented heterobimetallic [CrIII(μ‐O2)Li+] core; beyond this it is the first chromium superoxide for which a temperature‐dependent magnetic characterization could be achieved, and the first structurally characterized representative with chromium in an exclusive O‐donor environment.
Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution, Cells, and Mice
Authors: Chaves‐Ferreira Miguel , Albuquerque Inês S. , Matak‐Vinkovic Dijana , Coelho Ana C. , Carvalho Sandra M. , Saraiva Lígia M. , Romão Carlos C. , Bernardes Gonçalo J. L.
Published: December 2014

We demonstrate that RuII(CO)2–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac‐RuCl(κ2‐H2NCH2CO2)(CO)3] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–RuII(CO)2 complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–RuII(CO)2 in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of RuII(CO)2–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.
Assessing the Viability of Extended Nonmetal Atom Chains in MnF4n+2 (M=S and Se)
Authors: Popov Ivan A. , Averkiev Boris B. , Starikova Alyona A. , Boldyrev Alexander I. , Minyaev Ruslan M. , Minkin Vladimir I.
Published: December 2014

Theoretical investigations to evaluate the viability of extended nonmetal atom chains on the basis of molecular models with the general formula MnF4n+2 (M=S and Se) and corresponding solid‐state systems exhibiting direct SS or SeSe bonding were performed. The proposed high‐symmetry molecules were found to be minima on the potential energy surface for all SnF4n+2 systems studied (n=2–9) and for selenium analogues up to n=6. Phonon calculations of periodic structures confirmed the dynamic stability of the ‐(SF4–SF4)∞‐ chain, whereas the analogous ‐(SeF4–SeF4)∞‐ chain was found to have a number of imaginary phonon frequencies. Chemical bonding analysis of the dynamically stable ‐(SF4–SF4)∞‐ structure revealed a multicenter character of the SS and SF bonds. A novel definition and abbreviation (ENAC) are proposed by analogy with extended metal atom chain (EMAC) complexes.
A Neutral Tetraphosphacyclobutadiene Ligand in Cobalt(I) Complexes
Authors: Yao Shenglai , Lindenmaier Nils , Xiong Yun , Inoue Shigeyoshi , Szilvási Tibor , Adelhardt Mario , Sutter Jörg , Meyer Karsten , Driess Matthias
Published: December 2014

The unusual reactivity of the newly synthesized β‐diketiminato cobalt(I) complexes, [(LDepCo)2] (2 a, LDep=CH[C(Me)N(2,6‐Et2C6H3)]2) and [LDippCo⋅toluene] (2 b, LDipp=CH[CHN(2,6‐iPr2C6H3)]2), toward white phosphorus was investigated, affording the first cobalt(I) complexes [(LDepCo)2(μ2:η4,η4‐P4)] (3 a) and [(LDippCo)2(μ2:η4,η4‐P4)] (3 b) bearing the neutral cyclo‐P4 ligand with a rectangular‐planar structure. The redox chemistry of 3 a and 3 b was studied by cyclic voltammetry and their chemical reduction with one molar equivalent of potassium graphite led to the isolation of [(LDepCo)2(μ2:η4,η4‐P4)][K(dme)4] (4 a) and [(LDippCo)2(μ2:η4,η4‐P4)][K(dme)4] (4 b). Unexpectedly, the monoanionic Co2P4 core in 4 a and 4 b, respectively, contains the two‐electron‐reduced cyclo‐P42− ligand with a square‐planar structure and mixed‐valent cobalt(I,II) sites. The electronic structures of 3 a, 3 b, 4 a, and 4 b were elucidated by NMR and EPR spectroscopy as well as magnetic measurements and are in agreement with results of broken‐symmetry DFT calculations.
Chemical Reactivity on Gas‐Phase Metal Clusters Driven by Blackbody Infrared Radiation
Authors: Parry Imogen S. , Kartouzian Aras , Hamilton Suzanne M. , Balaj O. Petru , Beyer Martin K. , Mackenzie Stuart R.
Published: December 2014

We report the observation of chemical reactions in gas‐phase Rhn(N2O)m+ complexes driven by absorption of blackbody radiation. The experiments are performed under collision‐free conditions in a Fourier transform ion cyclotron resonance mass spectrometer. Mid‐infrared absorption by the molecularly adsorbed N2O moieties promotes a small fraction of the cluster distribution sufficiently to drive the N2O decomposition reaction, leading to the production of cluster oxides and the release of molecular nitrogen. N2O decomposition competes with molecular desorption and the branching ratios for the two processes show marked size effects, reflecting variations in the relative barriers. The rate of decay is shown to scale approximately linearly with the number of infrared chromophores. The experimental findings are interpreted in terms of calculated infrared absorption rates assuming a sudden‐death limit.
X‐Ray Characterization of an Electron Donor–Acceptor Complex that Drives the Photochemical Alkylation of Indoles
Authors: Kandukuri Sandeep R. , Bahamonde Ana , Chatterjee Indranil , Jurberg Igor D. , Escudero‐Adán Eduardo C. , Melchiorre Paolo
Published: December 2014

A metal‐free, photochemical strategy for the direct alkylation of indoles was developed. The reaction, which occurs at ambient temperature, is driven by the photochemical activity of electron donor–acceptor (EDA) complexes, generated upon association of substituted 1H‐indoles with electron‐accepting benzyl and phenacyl bromides. Significant mechanistic insights are provided by the X‐ray single‐crystal analysis of an EDA complex relevant to the photoalkylation and the determination of the quantum yield (Φ) of the process.
The Reactivities of Iminoboranes with Carbenes: BN Isosteres of Carbene–Alkyne Adducts
Authors: Braunschweig Holger , Ewing William C. , Geetharani K. , Schäfer Marius
Published: December 2014

The first examples of adducts of cyclic alkyl(amino) carbenes (CAAC) and N‐heterocyclic carbenes (NHCs) with iminoboranes have been synthesized and isolated at low temperature (−45 °C). The adducts show short BN bonds and planarity at boron, mimicking the structures of the isoelectronic imine functionality. When di‐tert‐butyliminoborane was reacted with 1,3‐bis(isopropyl)imidazol‐2‐ylidene (IPr), the initially formed Lewis acid–base adduct quickly rearranged to form a new carbene substituted with an aminoborane at the 4‐position. Warming the iminoborane–CAAC adduct to room temperature resulted in an intramolecular cyclization to give a bicyclic 1,2‐azaborilidine compound.
SN2P2: A Neutral Five‐Membered Sulfur–Pnictogen(III) Ring
Authors: Zeng Xiaoqing , Li Hongmin , Sun Hailong , Beckers Helmut , Willner Helge , Schaefer Henry F.
Published: December 2014

The novel aromatic ring compound 2,4‐diphospha‐3,5‐diaza‐thiole (cyclo‐SNPNP) was synthesized via flash pyrolysis of SP(N3)3 and characterized by IR spectroscopy and 15N isotope labeling. Quantum chemical computations indicate its formation by head‐to‐tail dimerization of SNP and subsequent elimination of a sulfur atom from the highly unstable boatlike six‐membered‐ring compound cyclo‐SNPSNP.
Enantioselective Synthesis of α‐Aminosilanes by Copper‐Catalyzed Hydroamination of Vinylsilanes
Authors: Niljianskul Nootaree , Zhu Shaolin , Buchwald Stephen L.
Published: December 2014

The synthesis of α‐aminosilanes by a highly enantio‐ and regioselective copper‐catalyzed hydroamination of vinylsilanes is reported. The system employs Cu‐DTBM‐SEGPHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O‐benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds.
Total Synthesis of (±)‐Hippolachnin A
Authors: Ruider Stefan A. , Sandmeier Tobias , Carreira Erick M.
Published: December 2014

The first total synthesis of the marine polyketide (±)‐hippolachnin A has been achieved in nine linear steps and an overall yield of 9 %. Rapid access to the oxacyclobutapentalene core structure was secured by strategic application of an ene cyclization.
Palladium‐Catalyzed Intramolecular CH Difluoroalkylation: Synthesis of Substituted 3,3‐Difluoro‐2‐oxindoles
Authors: Shi Shi‐Liang , Buchwald Stephen L.
Published: December 2014

The synthesis of 3,3‐difluoro‐2‐oxindoles through a robust and efficient palladium‐catalyzed CH difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate‐determining step for this process.
Towards Maintenance‐Free Biosensors for Hundreds of Bind/Release Cycles
Authors: Potyrailo Radislav A. , Murray Anthony J. , Nagraj Nandini , Pris Andrew D. , Ashe Jeffrey M. , Todorovic Milos
Published: December 2014

A single aptamer bioreceptor layer was formed using a common streptavidin–biotin immobilization strategy and employed for 100–365 bind/release cycles. Chemically induced aptamer unfolding and release of its bound target was accomplished using alkaline solutions with high salt concentrations or deionized (DI) water. The use of DI water scavenged from the ambient atmosphere represents a first step towards maintenance‐free biosensors that do not require the storage of liquid reagents. The aptamer binding affinity was determined by surface plasmon resonance and found to be almost constant over 100–365 bind/release cycles with a variation of less than 5 % relative standard deviation. This reversible operation of biosensors based on immobilized aptamers without storage of liquid reagents introduces a conceptually new perspective in biosensing. Such new biosensing capability will be important for distributed sensor networks, sensors in resource‐limited settings, and wearable sensor applications.
Negative Interplay of Retinoic Acid and TGF‐β Signaling Mediated by TG‐Interacting Factor to Modulate Mouse Embryonic Palate Mesenchymal–Cell Proliferation
Authors: Liu Xiaozhuan , Zhang Huanhuan , Gao Liyun , Yin Yanyan , Pan Xinjuan , Li Zhitao , Li Ning , Li Haozhe , Yu Zengli
Published: December 2014

Mesenchymal‐cell proliferation is the main process in shelf outgrowth. Both all‐trans‐retinoic acid (atRA) and transforming growth factor‐β3 (TGF‐β3) play an important role in mouse embryonic palate mesenchymal (MEPM) cell proliferation. In the present study, we investigated the crosstalk between RA and TGF‐β signaling in MEPM‐cell proliferation. We found that atRA inhibited MEPM‐cell proliferation by downregulating TGF‐β/Smad signaling and that TGF‐β3 treatment was able to antagonize RA signaling. Transforming growth–interacting factor (TGIF) is a transcriptional repressor that suppresses both TGF‐β‐ and retinoid‐driven gene transcription. Furthermore, we investigated the role of TGIF in the interaction between both TGF‐β and RA signaling in MEPM‐cell proliferation. The results showed that both atRA and TGF‐β3 significantly increased the expression level of TGIF, and TGIF mediated the negative interaction between TGF‐β and RA signaling pathways, which depended on TGIF binding to Smad2 or RARβ (RA receptor beta). Moreover, after deletion of TGIF, both the effects of atRA on TGF‐β‐dependent protein expression and the effects of TGF‐β on RA‐dependent protein expression were lost. So we conclude that there is a negative functional interplay of RA and TGF‐β signaling mediated by TGIF to modulate MEPM‐cell proliferation
Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues
Authors: Spade Daniel J. , McDonnell Elizabeth V. , Heger Nicholas E. , Sanders Jennifer A. , Saffarini Camelia M. , Gruppuso Philip A. , De Paepe Monique E. , Boekelheide Kim
Published: December 2014

Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human‐relevant mechanistic data on the many tissue‐level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development
Close Link between Protoporphyrin IX Accumulation and Developmental Toxicity Induced by N‐Phenylimide Herbicides in Rats
Authors: Kawamura Satoshi , Kato Terushige , Fantel Alan G.
Published: December 2014

BACKGROUND

S‐53482, 7‐fluoro‐6‐[(3,4,5,6‐tetrahydro)phthalimido]‐4‐(2‐propynyl)‐1,4‐benzoxazin‐3(2H)‐one (flumioxazin), is an N‐phenylimide herbicide and developmentally toxic to rats, but not to rabbits. The day of greatest sensitivity to S‐53482 is gestational day (GD) 12 in rats. There is a compound‐specific difference in developmental toxicity among structurally similar compounds including S‐23121 (N‐[4‐chloro‐2‐fluoro‐5‐[(1‐methyl‐2‐propynyl)oxy]phenyl]‐3,4,5,6‐tetrahydrophthalimide; teratogenic) and S‐23031 (pentyl 2‐chloro‐4‐fluoro‐5‐(3,4,5,6‐tetrahydrophthalimido)phenoxyacetate (flumiclorac pentyl); nonteratogenic). The herbicidal action is due to photodynamic action of accumulating protoporphyrin IX (PPIX), resulting from the inhibition of protoporphyrinogen oxidase (PPO), an enzyme in porphyrin biosynthesis. Species difference in PPIX accumulation in embryos corresponded to those of the developmental toxicity. Our objective in this study was to further investigate a link between PPIX accumulation resulting from PPO inhibition and developmental toxicity. This article is part of a series of studies to be published serially.

METHODS

To investigate compound‐specific differences, each compound was orally administered to rats on GD 12. To define peak period of PPIX accumulation, single oral treatments of S‐53482 were given to rats or rabbits at 19:30 on GD 10 through GD 15. PPIX was extracted from embryos 14 hr after treatment.

RESULTS

Remarkable PPIX accumulation was observed when treated with S‐53482 or S‐23121, but not with S‐23031. The greatest accumulation of PPIX was observed when treated with S‐53482 at 19:30 on GD 11 or GD 12. No PPIX accumulation was found on any GDs in rabbits.

CONCLUSIONS

The developmentally toxic compounds caused PPIX accumulation in embryos. The peak period of PPIX accumulation corresponded to that of developmental effects. This correlation suggests a close link between PPO inhibition and developmental abnormality
Human Serum Transferrin Fibrils: Nanomineralisation in Bacteria and Destruction of Red Blood Cells
Authors: Mukherjee Arindam , Barnett Mark A. , Venkatesh V. , Verma Sandeep , Sadler Peter J.
Published: December 2014

Fibrils formed by human serum transferrin [(1–3 μM) apo‐Tf, partially iron‐saturated (Fe0.6‐Tf) and holo‐Tf (Fe2‐Tf) forms], from dilute bicarbonate solutions, were deposited on formvar surfaces and studied by electron microscopy. We observed that possible bacterial contamination appears to give rise to long, pea‐pod‐like (PPL) structures for Fe2‐Tf, attributable to the formation of polyhydroxybutyrate (PHB) storage granules, under the nutrient‐limiting conditions used. These PPL structures contained periodic nanomineralisation sites susceptible to uranyl stain. Extended incubation of transferrin solutions (about four days) gave rise to extensive transferrin fibril structures. Optical microscopy and AFM studies showed that red blood cells (RBCs) readily adhere to these fibrils. Moreover, the fibrils appear to penetrate RBC membranes and to induce rapid cell destruction (within about 5 h). It is speculated that in situations in vivo where transferrin fibrils can form, such interactions might have adverse physiological consequences, and further studies could aid the understanding of related pathological events.
Elucidating the Catalytic Subunit Composition of Distinct Proteasome Subtypes: A Crosslinking Approach Employing Bifunctional Activity‐Based Probes
Authors: Cornish Carmony Kimberly , Sharma Lalit Kumar , Lee Do‐Min , Park Ji Eun , Lee Wooin , Kim Kyung‐Bo
Published: December 2014

In addition to two well‐recognized proteasome subtypes—constitutive proteasomes and immunoproteasomes—mounting evidence also suggests the existence of intermediate proteasome subtypes containing unconventional mixtures of catalytic subunits. Although they appear to play unique biological roles, the lack of practical methods for detecting distinct proteasome subtypes has limited functional investigations. Here, we report the development of activity‐based probes that crosslink two catalytic subunits within intact proteasome complexes. Identification of the crosslinked subunit pairs provides direct evidence of the catalytic subunit composition of proteasomes. Using these probes, we found that U266 multiple myeloma cells contain intermediate proteasomes comprising both β1i and β2, but not β1 and β2i, consistent with previous findings with other cell types. Our bifunctional probes can be utilized in functional investigations of distinct proteasome subtypes in various biological settings.
GLUE That Sticks to HIV: A Helix‐Grafted GLUE Protein That Selectively Binds the HIV gp41 N‐Terminal Helical Region
Authors: Walker Susanne N. , Tennyson Rachel L. , Chapman Alex M. , Kennan Alan J. , McNaughton Brian R.
Published: December 2014

Methods for the stabilization of well‐defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Here, we report the stable and functional display of an HIV gp41 C‐peptide helix mimic on a GRAM‐Like Ubiquitin‐binding in EAP45 (GLUE) protein. C‐peptide helix‐grafted GLUE selectively binds a mimic of the N‐terminal helical region of gp41, a well‐established HIV drug target, in a complex cellular environment. Additionally, the helix‐grafted GLUE is folded in solution, stable in human serum, and soluble in aqueous solutions, and thus overcomes challenges faced by a multitude of peptide drugs, including those derived from HIV gp41 C‐peptide.
Hydrogen‐Bonding‐Driven Enantioselective Resolution against the Kazlauskas Rule To Afford γ‐Amino Alcohols by Candida rugosa Lipase
Authors: Min Bora , Park Jeemin , Sim Yong‐Kyun , Jung Suhyun , Kim Seong‐Ho , Song Jae Kwang , Kim Bum Tae , Park Sang Youn , Yun Jaesook , Park Seongsoon , Lee Hyuk
Published: December 2014

Most lipases resolve secondary alcohols in accordance with the “Kazlauskas rule” to give the R enantiomers. In a similar manner to other lipases, Candida rugosa lipase (CRL) exhibits R enantioselectivity towards heptan‐2‐ol, although the enantiomeric ratio (E) is low (E=1.6). However, unexpected enantioselectivity (i.e., S enantioselectivity, E=58) of CRL towards 4‐(tert‐butoxycarbonylamino)butan‐2‐ol, which has a similar chain length to heptan‐2‐ol, has been observed. To develop a deeper understanding of the molecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of these computational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S enantiomer.
One‐pot Conversion of Cycloalkanes to Lactones
Authors: Pennec Alizé , Hollmann Frank , Smit Martha S. , Opperman Diederik J.
Published: December 2014

The one‐pot conversion of cycloalkanes to their corresponding lactones was achieved through the use of a synthetic pathway consisting of a cytochrome P450 monooxygenase (CYP450) for initial oxyfunctionalization of the cycloalkane, an alcohol dehydrogenase for ketone production and a Baeyer–Villiger monooxygenase for lactone formation. Through variation of the cofactor dependence of the biocatalysts and the cofactor regeneration system, final product concentrations of nearly 3 g L−1 enantholactone (2‐oxocanone) from cycloheptane was reached within 12 h with a total turnover number (TTN) of 4185 with respect to the CYP450.
Synthesis of Palladium Colloidal Nanocrystal Clusters and Their Enhanced Electrocatalytic Properties
Authors: Ding Ruixue , Wu Xinyan , Han Guangting , Wang Qinchao , Lu Hailong , Li Hongliang , Fu Aiping , Guo Peizhi
Published: December 2014

Colloidal nanocrystal clusters (CNCs) and nanoparticles of palladium (Pd) were synthesized controllably by using an amino‐acid‐assisted hydrothermal method in the presence of polyvinylpyrrolidone. Experimental results showed that crystalline Pd nanoparticles were synthesized by adding alanine into the synthetic solutions, whereas sub‐micrometer Pd CNCs composed of small nanocrystals were obtained from phenylalanine systems. Electrochemical measurements showed that Pd CNCs displayed a much better electrocatalytic performance than nanoparticles, because CNCs were formed by the in situ self‐assembly of primary nanocrystals. The structure of Pd CNCs can also be maintained after electrocatalytic cycle testing. Both Pd‐based electrocatalysts showed the highest electrocatalytic activity towards the electrooxidation of ethanol among the used alcohols. The formation mechanisms and electrocatalytic properties of the Pd nanoparticles and CNCs are discussed and analyzed based on the experimental data.
Redox‐ and Protonation‐Induced Fluorescence Switch in a New Triphenylamine with Six Stable Active or Non‐Active Forms
Authors: Quinton Cassandre , Alain‐Rizzo Valérie , Dumas‐Verdes Cécile , Miomandre Fabien , Clavier Gilles , Audebert Pierre
Published: December 2014

The synthesis, photophysical and electrochemical properties as well as theoretical calculation studies of a newly designed triphenylamine derivative are described. This original compound displays one neutral form, three oxidized forms, and two protonated forms with distinct photophysical characteristics. The interplay of the emission with the protonation or the redox state (electrofluorochromism) has been explored and an on–off–on–off fluorescence switching was observed in the case of oxidation and an on–on–off fluorescence switching in the case of protonation.
Phosphinoyl and Thiophosphinoylcarbodithioates: Synthesis, Molecular Structure, and Application as New Efficient Mediators for RAFT Polymerization
Authors: Mazières Stéphane , Kulai Ihor , Geagea Roland , Ladeira Sonia , Destarac Mathias
Published: December 2014

New phosphinoyl and thiophosphinoylcarbodithioates were synthesized in a one‐pot reaction from the corresponding phosphinochalcogenides. Compounds of this new generation of thiocarbonylthio derivatives have been fully characterized by IR as well as 1H, 31P, and 13C NMR spectroscopy and by mass spectrometry. Their solid‐state structures reveal that they are isostructural but crystallize in different space groups. These new compounds are highly efficient reversible chain‐transfer agents for the reversible addition‐fragmentation chain transfer (RAFT) polymerization of styrene (St) and n‐butyl acrylate (nBA), with controlled number‐average molecular weights (Mn) and narrow dispersity values (Ð<1.3). The controlled character of the polymerization was further exemplified by MALDI‐TOF mass spectrometry and the synthesis of PSt‐P(nBA) diblock copolymers.
Single‐Crystal‐to‐Single‐Crystal Transformation and Solvochromic Luminescence of a Dinuclear Gold(I)–(Aza‐[18]crown‐6)dithiocarbamate Compound
Authors: Tzeng Biing‐Chiau , Chao An
Published: December 2014

The treatment of [AuCl(SMe2)] with an equimolar amount of NaO5NCS2 (O5NCS2=(aza‐[18]crown‐6)dithiocarbamate) in CH3CN gave [Au2(O5NCS2)2]⋅2 CH3CN (2⋅2 CH3CN), and its crystal structure displays a dinuclear gold(I)‐azacrown ether ring and an intermolecular gold(I)⋅⋅⋅gold(I) contact of 2.8355(3) Å in crystal lattices. It is noted that two other single crystals of 2⋅tert‐butylbenzene⋅H2O and 2⋅0.5 m‐xylene can be successfully obtained from a single‐crystal‐to‐single‐crystal (SCSC) transformation process by immersing single crystals of 2⋅2 CH3CN in the respective solvents, and both also show intermolecular gold(I)⋅⋅⋅gold(I) contacts of 2.9420(5) and 2.890(2)–2.902(2) Å, respectively. Significantly, the emissions of all three 2⋅solvates are well correlated with their respective intermolecular gold(I)⋅⋅⋅gold(I) contacts, where such contacts increase with 2⋅2 CH3CN (2.8355(3) Å)<2⋅0.5 m‐xylene (2.890(2)–2.902(2) Å)<2⋅tert‐butylbenzene⋅H2O (2.9420(5) Å), and their emission energies increase with 2⋅2 CH3CN (602 nm)<2⋅0.5 m‐xylene (583 nm)<2⋅tert‐butylbenzene⋅H2O (546 nm) as well. In this regard, we further examine the solvochromic luminescence for some other aromatics, and finally their emissions are within 546–602 nm. Obviously, the above results are mostly ascribed to the occurrence of intermolecular gold(I)⋅⋅⋅gold(I) contacts in 2⋅solvates, which are induced by the presence of various solvates in the solid state, as a key role to be responsible for their solvochromic luminescence.
Ln3Q9 as a Molecular Framework for Ion‐Size‐Driven Assembly of Heterolanthanide (Nd, Er, Yb) Multiple Near‐Infrared Emitters
Authors: Artizzu Flavia , Quochi Francesco , Marchiò Luciano , Correia Raquel Fonseca , Saba Michele , Serpe Angela , Mura Andrea , Mercuri Maria Laura , Bongiovanni Giovanni , Deplano Paola
Published: December 2014

A unique example of discrete molecular entity NdyErxYb3−(x+y)Q9 (1) (Q=quinolinolato) containing three different lanthanides simultaneously emitting in three different spectral regions in the NIR, ranging from 900 to 1600 nm, has been synthesized and fully chararacterized. A simple molecular strategy based on tuning metal composition in the Ln3Q9 framework, which contains inequivalent central and terminal coordination sites, has allowed a satisfactory ion‐size‐driven control of molecular speciation close to 90 %. In 1 the central position of the larger Nd ion is well distinguished from the terminal ones of the smaller Yb3+ and Er3+, which are almost “vicariants” as found in the heterobimetallic ErxYb3−xQ9 (2). The Ln3Q9 molecular architecture, which allows communication between the ions, has proved to afford multiple NIR emission in 1 and 2, and is promising to develop a variety of multifunctional materials through the variation of the Ln composition.
Synthesis of Bridged Benzazocines and Benzoxocines by a Titanium‐Catalyzed Double‐Reductive Umpolung Strategy
Authors: Bichovski Plamen , Haas Thomas M. , Kratzert Daniel , Streuff Jan
Published: December 2014

A sequence of two titanium(III)‐catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo‐ and benzoxozine building blocks. The first step is a reductive cross‐coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn‐selectivity for the quinolone functionalization while the anti‐diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn‐chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X‐ray analyses and 2D NMR spectroscopic experiments.