bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoothed estimation of unknown inputs and states in dynamic systems with application to oceanic flow field reconstruction
Authors: Fang Huazhen , de Callafon Raymond A. , Franks Peter J. S.
Published: December 2014

Forward‐backward smoothing based unknown input and state estimation for dynamic systems is studied in this paper, motivated by reconstruction of an oceanographic flow field using a swarm of buoyancy‐controlled drifters. The development is conducted in a Bayesian framework. A Bayesian paradigm is constructed first to offer a probabilistic view of the unknown quantities given the measurements. Then a maximum a posteriori is established to build a means for simultaneous input and state smoothing, which can be solved by the classical Gauss–Newton method in the nonlinear case. Application to reconstruction of a complex three‐dimensional flow field is presented and investigated via simulation studies. Copyright © 2014 John Wiley & Sons, Ltd.
A Timely Synthetic Tailoring of Biaxially Extended Thienylenevinylene‐Like Polymers for Systematic Investigation on Field‐Effect Transistors
Authors: Yoo Dohyuk , Nketia‐Yawson Benjamin , Kang Seok‐Ju , Ahn Hyungju , Shin Tae Joo , Noh Yong‐Young , Yang Changduk
Published: December 2014

Considering there is growing interest in the superior charge transport in the (E)‐2‐(2‐(thiophen‐2‐yl)‐vinyl)thiophene (TVT)‐based polymer family, an essential step forward is to provide a deep and comprehensive understanding of the structure–property relationships with their polymer analogs. Herein, a carefully chosen set of DPP‐TVT‐n polymers are reported here, involving TVT and diketopyrrolopyrrole (DPP) units that are constructed in combination with varying thiophene content in the repeat units, where n is the number of thiophene spacer units. Their OFET characteristics demonstrate ambipolar behavior; in particular, with DPP‐TVT‐0 a nearly balanced hole and electron transport are observed. Interestingly, the majority of the charge‐transport properties changed from ambipolar to p‐type dominant, together with the enhanced hole mobilities, as the electron‐donating thiophene spacers are introduced. Although both the lamellar d‐spacings and π‐stacking distances of DPP‐TVT‐n decreased with as the number of thiophene spacers increased, DPP‐TVT‐1 clearly shows the highest hole mobility (up to 2.96 cm2 V−1 s−1) owing to the unique structural conformations derived from its smaller paracrystalline distortion parameter and narrower plane distribution relative to the others. These in‐depth studies should uncover the underlying structure–property relationships in a relevant class of TVT‐like semiconductors, shedding light on the future design of top‐performing semiconducting polymers.
The Lithium/Air Battery: Still an Emerging System or a Practical Reality?
Authors: Grande Lorenzo , Paillard Elie , Hassoun Jusef , Park Jin‐Bum , Lee Yung‐Jung , Sun Yang‐Kook , Passerini Stefano , Scrosati Bruno
Published: December 2014

Lithium/air is a fascinating energy storage system. The effective exploitation of air as a battery electrode has been the long‐time dream of the battery community. Air is, in principle, a no‐cost material characterized by a very high specific capacity value. In the particular case of the lithium/air system, energy levels approaching that of gasoline have been postulated. It is then not surprising that, in the course of the last decade, great attention has been devoted to this battery by various top academic and industrial laboratories worldwide. This intense investigation, however, has soon highlighted a series of issues that prevent a rapid development of the Li/air electrochemical system. Although several breakthroughs have been achieved recently, the question on whether this battery will have an effective economic and societal impact remains. In this review, a critical evaluation of the progress achieved so far is made, together with an attempt to propose future R&D trends. A forecast on whether Li/air may have a role in the next years' battery technology is also postulated.
Lewis Acid‐Catalyzed Generation of CC and CN Bonds on π‐Deficient Heterocyclic Substrates
Authors: Staderini Matteo , Bolognesi Maria Laura , Menéndez J. Carlos
Published: December 2014

Focused microwave irradiation of a series of halogenated nitrogen heterocycles and different kinds of nucleophiles in the presence of a catalytic amount of indium trichloride leads to the efficient and completely regioselective generation of aromatic CC and CN bonds. The method is simple, rapid, general and inexpensive, and can be performed without the use of dried solvents. Most of the synthetized compounds are new and in many cases the work‐up required only filtration. Furthermore, this is the first example of the use of a Lewis acid as a catalyst for heteroarylation, vinylation and amination reactions on π‐deficient heterocyclic substrates.

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Novel DNA Catalysts Based on G‐Quadruplex for Organic Synthesis
Authors: Wang Li‐Xia , Xiang Jun‐Feng , Tang Ya‐Lin
Published: December 2014

Double‐stranded DNA (dsDNA) as a catalytic species has been applied in various key asymmetric reactions. Compared with dsDNA, G‐quadruplex DNAs (G4DNAs) have unique conformational structures and versatile complexation properties, and act expectedly as hosts to recognize planar aromatic molecules through π–π stacking. Based on the specific recognition for small molecules, G4DNA‐based catalysts have been used to assist the catalytic function, and have been applied in asymmetric organic reactions.

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Material properties and operating configurations of membrane reactors for propane dehydrogenation
Authors: Choi Seung‐Won , Jones Christopher W. , Nair Sankar , Sholl David S. , Moore Jason S. , Liu Yujun , Dixit Ravindra S. , Pendergast John G.
Published: December 2014

A modeling‐based approach is presented to understand physically realistic and technologically interesting material properties and operating configurations of packed‐bed membrane reactors (PBMRs) for propane dehydrogenation (PDH). PBMRs composed of microporous or mesoporous membranes combined with a PDH catalyst are considered. The influence of reaction and membrane transport parameters, as well as operating parameters such as sweep flow and catalyst placement, are investigated to determine desired “operating windows” for isothermal and nonisothermal operation. Higher Damköhler (Da) and lower Péclet (Pe) numbers are generally helpful, but are much more beneficial with highly H2‐selective membranes rather than higher‐flux, lower‐selectivity membranes. H2‐selective membranes show a plateau region of conversion that can be overcome by a large sweep flow or countercurrent operation. The latter shows a complex trade‐off between kinetics and permeation, and is effective only in a limited window. H2‐selective PBMRs will greatly benefit from the fabrication of thin (∼1 µm or less) membranes. © 2014 American Institute of Chemical Engineers AIChE J, 61: 922–935, 2015
Association of the blood eosinophil count with hematological malignancies and mortality
Authors: Andersen Christen L. , Siersma Volkert D. , Hasselbalch Hans C. , Vestergaard Hanne , Mesa Ruben , Felding Peter , Olivarius Niels D.F. , Bjerrum Ole W.
Published: December 2014

Blood eosinophilia (≥0.5 × 109/l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut‐offs for referral to specialist hematology care. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000–2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable logistic regression to calculate odds ratios (ORs) for the 4‐year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16 × 109/l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above the median eosinophil count. At the 99th percentile, corresponding to an eosinophil count of 0.75 × 109/l, risks of hematological malignancies were increased more than twofold with OR (95% C.I.) of 2.39 (1.91–2.99). Interestingly, risks reached a plateau around an eosinophil count of 1.0 × 109/l. Risks also increased when the eosinophil count approached zero. Here, counts associated relatively more with acute myeloid leukemia and myelodysplastic syndromes whereas counts above 0.16 × 109/l associated more with myeloproliferative neoplasms. Eosinophil counts associate with hematological malignancies and mortality even below the definition of eosinophilia. The observed plateau of risks around 1.0 × 109/l is important for physicians encountering patients with eosinophilia since even mild‐to‐moderate eosinophilia according to traditional definitions confers maximally increased risks of subsequent/subclinical hematological malignancy. Am. J. Hematol. 90:225–229, 2015. © 2014 Wiley Periodicals, Inc.
Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation
Authors: Karaer Kadri , Lissewski Christina , Zenker Martin
Published: December 2014

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals. © 2014 Wiley Periodicals, Inc.
Microdeletion of 19p13.3 in a girl with Peutz–Jeghers syndrome, intellectual disability, hypotonia, and distinctive features
Authors: Kuroda Yukiko , Saito Toshiyuki , Nagai Jun‐Ichi , Ida Kazumi , Naruto Takuya , Masuno Mitsuo , Kurosawa Kenji
Published: December 2014

Peutz–Jeghers syndrome (PJS) is a rare autosomal dominant disease characterized by gastrointestinal polyposis and mucocutaneous pigmentation. Germline point mutations in the serine/threonine kinase 11 (STK11) have been identified in about 70% of patients with PJS. Only a few large genomic deletions have been identified. We report on a girl with PJS and multiple congenital anomalies. She had intellectual disability, umbilical hernia, bilateral inguinal hernias, scoliosis, and distinct facial appearance including prominent mandible, smooth philtrum, and malformed ears. She developed lip pigmentation at the age of 12 years but had no gastrointestinal polyps. Array comparative genomic hybridization revealed an approximately 610 kb deletion at 19p13.3, encompassing STK11. Together with previous reports, the identification of common clinical features suggests that microdeletion at 19p13.3 encompassing STK11 constitutes a distinctive phenotype. © 2014 Wiley Periodicals, Inc.
A new patient with LACHT syndrome (Mardini–Nyhan association)
Authors: Atik Tahir , Torun Huseyin Ozan , Cogulu Ozgur , Ozkinay Ferda
Published: December 2014

LACHT syndrome, Lung Agenesis, Congenital Heart defects, and Thumb anomalies, (Mardini–Nyhan Association OMIM #601612) is a rare condition characterized by unilateral or bilateral lung agenesis, complex cardiac defects, especially anomalous pulmonary venous return, and thumb anomalies. Based on previous cases, its inheritance pattern seems to be autosomal recessive. In 1985, the syndrome was firstly described by Mardini and Nyhan in four patients from unrelated families. Until now, a total of eight patients have been reported in the literature. Molecular cause of the disease is still unknown. Here, we report on a patient with LACHT syndrome diagnosed by clinical findings. In this study, we present a 4.5‐month‐old female infant with right lung agenesis and inguinal hernia, in which ovaries are revealed on ultrasonography. The infant was born to consanguineous parents following a 38th week of gestation, with a birth weight of 2,800 g. Overall development was consistent with age; she had thumb abnormalities. Echocardiography showed peripheral pulmonary stenosis. The girl was diagnosed as LACHT syndrome based on the findings of unilateral lung agenesis, thumb anomalies, and peripheral pulmonary stenosis. LACHT syndrome should be considered in the differential diagnosis of patients with unilateral or bilateral lung agenesis. Here, we report on the 9th case in the literature. The consanguinity of the parents supports autosomal inheritance as the genetic basis of LACHT syndrome. © 2014 Wiley Periodicals, Inc.
Synthesis of Allokainic Acid: A Review
Authors: Bhat Chinmay , Kumar Amit
Published: December 2014

This Focus Review discusses the synthesis of an important member of the kainoid family; allokainic acid. The members of the kainoid family have attracted worldwide attention since their first isolation in 1953 due to their vast and potential medicinal applications, especially in neuroscience. The review focuses on the synthesis of allokainic acid using different synthetic methods from its first synthesis to the most recent one, covering 1953‐2014.
The safety of self‐administered allergen immunotherapy during the buildup and maintenance phases
Authors: Schaffer Frederick M. , Naples Andrew R. , Ebeling Myla , Hulsey Thomas C. , Garner Larry M.
Published: December 2014

Background

Self‐administered allergen immunotherapy is considered controversial. We believe the implementation of a self‐administration protocol characterized by patient preselection and a slow buildup phase is safe.

Methods

We analyzed 23,614 patient records and associated immunotherapy injections for systemic reactions (SR) during a 1‐year period (2011 to 2012). SRs were graded in accordance with the World Allergy Organization (WAO) criteria.

Results

Thirty‐seven SRs were reported for 23,614 patients who self‐administered 2,021,600 injections yielding an annual SR rate of 0.16% (per patient) or 0.002% (per injection). Only 9 of 4643 pediatric (0.19%) and 28 of 18,971 adult patients (0.15%) experienced 1 or more SRs. No deaths (grade V SR) occurred. From 2009 through early 2014, over 90,000 patients received more than 10 million injections in accordance with the United Allergy Services (UAS) protocol without fatalities.

Conclusion

We believe this safety profile is due to a preselection of patients to exclude those with a high risk for adverse reactions and a slow immunotherapy buildup phase. In contrast, previous studies documented office‐based SRs ranging from approximately 3% to greater than 14%. Thus, the UAS home‐immunotherapy SR rate is significantly lower than office‐based immunotherapy SR rates (p < 0.0001). The enhanced safety of this protocol results in a decreased frequency and severity of SRs. This safety report, derived from analyses of one of the largest patient cohorts studied, corroborates and expands the observations of previous studies of self‐administered subcutaneous immunotherapy in a low‐risk patient population by assessing self‐administered allergen immunotherapy during the buildup and maintenance phases.
No evidence for human papillomavirus infection in focal cortical dysplasiaIIb
Authors: Coras Roland , Korn Klaus , Bien Christian G. , Kalbhenn Thilo , Rössler Karl , Kobow Katja , Giedl Johannes , Fleckenstein Bernhard , Blumcke Ingmar
Published: December 2014

Objective

The etiology of focal cortical dysplasia type IIb (FCDIIb) remains enigmatic in patients suffering from drug‐resistant epilepsy, and an aberrant activation of the mammalian target of rapamycin complex 1 signaling pathway (mTORC1) was detected in this developmental brain malformation. Recently, the human papillomavirus (HPV) oncoprotein E6 has been identified as a potent activator of mTORC1, and HPV16 E6 has been described to persist in balloon cells obtained from surgical FCDIIb specimens. Although this observation was replicated by an independent second report, it contradicts current knowledge of HPV biology. HPV infects the squamous or mucocutaneous epithelium; hematogenic spread into other tissues has not been observed. In addition, brain carcinogenesis has never been reported in FCDIIb patients. Herein, we have tried to confirm 2 previous reports of HPV16 E6 infection using an independent series of 14 surgical specimens with histopathologically confirmed FCDIIb.

Methods

Snap‐frozen FCDIIb specimens were tested for HPV DNA using the primer set for amplification of the complete E6 reading frame of HPV16 and 3 other sets of primers (2 consensus primer sets detecting multiple HPV genotypes, and another primer set specifically used for HPV16). Furthermore, formalin‐fixed and paraffin‐embedded histopathological preparations were immunohistochemically analyzed using previously described antibodies directed against the HPV E6 oncoprotein.

Results

All 14 FCDIIb specimens were negative for HPV DNA with all 4 primer sets. Antibodies directed against the HPV E6 epitope showed weak labeling of cytoplasm in balloon cells, as previously described in FCDIIb, but also in other cell populations.

Interpretation

Our data did not confirm previously reported evidence for HPV16 detection in FCDIIb. Ann Neurol 2015;77:312–319
Marriage of Scintillator and Semiconductor for Synchronous Radiotherapy and Deep Photodynamic Therapy with Diminished Oxygen Dependence
Authors: Zhang Chen , Zhao Kuaile , Bu Wenbo , Ni Dalong , Liu Yanyan , Feng Jingwei , Shi Jianlin
Published: December 2014

Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing‐radiation‐induced PDT agent, achieving synchronous radiotherapy and depth‐insensitive PDT with diminished oxygen dependence. In the core–shell CeIII‐doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the CeIII‐doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron–hole (e−–h+) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy.
Beeinflussung der Aufnahme und lysosomalen Azidifizierung durch die Steifigkeit kolloidaler Partikel in vitro
Authors: Hartmann Raimo , Weidenbach Marcel , Neubauer Martin , Fery Andreas , Parak Wolfgang J.
Published: December 2014

Das Aufnahmeverhalten von Zellen wird maßgeblich durch die physikalisch‐chemischen Eigenschaften kolloidaler Partikel bestimmt. Um die Auswirkungen mechanischer Steifigkeit auf den Endozytosevorgang zu untersuchen, wurde ausschließlich dieser Parameter variiert, während weitere Eigenschaften wie Größe, Form und Ladung konstant gehalten wurden. Durch die Analyse einzelner Partikel‐Trajektorien während des Aufnahmevorgangs ließen sich bei gleichzeitiger Aufzeichnung des lokalen pH‐Werts um jedes einzelne Partikel Rückschlüsse über den jeweiligen Endozytoseverlauf ziehen. Insgesamt ergeben sich genügend Anhaltspunkte dafür, dass weichere Partikel schneller in lysosomale Strukturen transportiert werden als steifere.
Highly Enantioselective Intermolecular Cross Rauhut–Currier Reaction Catalyzed by a Multifunctional Lewis Base Catalyst
Authors: Dong Xuelin , Liang Ling , Li Erqing , Huang You
Published: December 2014

The highly enantioselective intermolecular cross Rauhut–Currier reaction of different active olefins catalyzed by a multifunctional chiral Lewis base was reported. The RC products were obtained in excellent yields (up to 98 %), high chemo‐ and enantioselectivity (up to 96 % ee). The reaction could be performed on a gram scale using 1 mol % of the multifunctional phosphine catalyst.
High‐Resolution N6‐Methyladenosine (m6A) Map Using Photo‐Crosslinking‐Assisted m6A Sequencing
Authors: Chen Kai , Lu Zhike , Wang Xiao , Fu Ye , Luo Guan‐Zheng , Liu Nian , Han Dali , Dominissini Dan , Dai Qing , Pan Tao , He Chuan
Published: December 2014

N6‐methyladenosine (m6A) is an abundant internal modification in eukaryotic mRNA and plays regulatory roles in mRNA metabolism. However, methods to precisely locate the m6A modification remain limited. We present here a photo‐crosslinking‐assisted m6A sequencing strategy (PA‐m6A‐seq) to more accurately define sites with m6A modification. Using this strategy, we obtained a high‐resolution map of m6A in a human transcriptome. The map resembles the general distribution pattern observed previously, and reveals new m6A sites at base resolution. Our results provide insight into the relationship between the methylation regions and the binding sites of RNA‐binding proteins.
Terpenoid Biosynthesis Off the Beaten Track: Unconventional Cyclases and Their Impact on Biomimetic Synthesis
Authors: Baunach Martin , Franke Jakob , Hertweck Christian
Published: December 2014

Terpene and terpenoid cyclizations are counted among the most complex chemical reactions occurring in nature and contribute crucially to the tremendous structural diversity of this largest family of natural products. Many studies were conducted at the chemical, genetic, and biochemical levels to gain mechanistic insights into these intriguing reactions that are catalyzed by terpene and terpenoid cyclases. A myriad of these enzymes have been characterized. Classical textbook knowledge divides terpene/terpenoid cyclases into two major classes according to their structure and reaction mechanism. However, recent discoveries of novel types of terpenoid cyclases illustrate that nature’s enzymatic repertoire is far more diverse than initially thought. This Review outlines novel terpenoid cyclases that are out of the ordinary.
Stabilization of the Cysteine‐Rich Conotoxin MrIA by Using a 1,2,3‐Triazole as a Disulfide Bond Mimetic
Authors: Gori Alessandro , Wang Ching‐I A. , Harvey Peta J. , Rosengren K. Johan , Bhola Rebecca F. , Gelmi Maria L. , Longhi Renato , Christie Macdonald J. , Lewis Richard J. , Alewood Paul F. , Brust Andreas
Published: December 2014

The design of disulfide bond mimetics is an important strategy for optimising cysteine‐rich peptides in drug development. Mimetics of the drug lead conotoxin MrIA, in which one disulfide bond is selectively replaced of by a 1,4‐disubstituted‐1,2,3‐triazole bridge, are described. Sequential copper‐catalyzed azide–alkyne cycloaddition (CuAAC; click reaction) followed by disulfide formation resulted in the regioselective syntheses of triazole–disulfide hybrid MrIA analogues. Mimetics with a triazole replacing the Cys4–Cys13 disulfide bond retained tertiary structure and full in vitro and in vivo activity as norepinephrine reuptake inhibitors. Importantly, these mimetics are resistant to reduction in the presence of glutathione, thus resulting in improved plasma stability and increased suitability for drug development.
New polynomial strain energy function; application to rubbery circular cylinders under finite extension and torsion
Authors: Bahreman Marzieh , Darijani Hossein
Published: December 2014

In this article, a strain energy density function is proposed in terms of the principal invariants of the left Cauchy‐Green strain tensor for Rubber‐like materials. This model due to its mathematical structure lies in the category of polynomial hyperelastic models. To compare the performance of the proposed model with the Rivlin set, some test data of rubber‐like materials with pure homogeneous deformations are used. It is shown that the proposed model has better agreement with the test data compared to the selected model. As an application of the proposed model, it is used to obtain a closed form solution for analysis of rubbery solid circular cylinders with S‐shaped and semi J‐shaped mechanical behavior under the torsion superimposed on the axial extension. Moreover, the results predicted from the proposed model are compared to classic models to investigate the results accuracy for simplification done. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41718.
Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy
Authors: Togami Kohei , Kanehira Yukimune , Tada Hitoshi
Published: December 2014

Pirfenidone is the first and only clinically used anti‐fibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). It was reported previously that pirfenidone metabolites (5‐hydroxypirfenidone and 5‐carboxypirfenidone) also have anti‐fibrotic effects. The present study evaluated the distribution of pirfenidone and its metabolites in the lung, liver and kidney tissues in rats. The time course for the different concentrations of pirfenidone, 5‐hydroxypirfenidone and 5‐carboxypirfenidone in the lung tissue following oral administration (30 mg/kg) to rats was lower than that in plasma, and the area under the drug concentration–time curve (AUC) ratios of lung/plasma for pirfenidone, 5‐hydroxypirfenidone and 5‐carboxypirfenidone were 0.52, 0.40 and 0.61, respectively. In in vitro transport experiments, the basolateral‐to‐apical transport of pirfenidone and its metabolites through the model of lung epithelial cell (Calu‐3) monolayers was not significantly different from their apical‐to‐basolateral transport. In binding experiments, the binding rate of these drugs to the lung tissue was lower than that to the plasma protein. These findings suggest that the low distribution of pirfenidone and its metabolites in the lungs was based on their low affinities with lung tissue and not the transport characteristics of lung epithelial cells. On the other hand, the AUC ratios of liver/plasma for pirfenidone and 5‐carboxypirfenidone were 2.3 and 6.5 and the AUC ratios of kidney/plasma were 1.5 and 20, respectively. The binding rates to the liver and kidney tissues were higher than those to the plasma protein. These results suggest that high concentrations of these drugs were found in the liver and kidney tissues. Copyright © 2014 John Wiley & Sons, Ltd.
Computational modeling and experimental validation of odor detection behaviors of classically conditioned parasitic wasp, Microplitis croceipes
Authors: Zhou Zhongkun , Kulasiri Don , Samarasinghe Sandhya , Rains Glen , Olson Dawn M.
Published: December 2014

A prototype chemical sensor named Wasp hound® that utilizes five classically conditioned parasitoid wasps, Microplitis croceipes (Cresson) (Hymenoptera: Braconidae), to detect volatile odors was successfully implemented in a previous study. To improve the odor‐detecting ability of Wasp Hound®, searching behaviors of an individual wasp in a confined area are studied and modeled through stochastic differential equations in this paper. The wasps are conditioned to 20 mg of coffee when associated with food and subsequently, tested to 5, 10, 20, and 40 mg of coffee. A stochastic model is developed and validated based on three positive behavioral responses (walking, rotation around odor source, and self‐rotation) from conditioned wasps at four different test dosages. The model is capable to reproducing the behaviors of conditioned wasps, and can be used to improve the ability of Wasp Hound® to assess changes in odor concentration. The model simulation results show the behaviors of conditioned wasps are significantly different when tested at different coffee dosages. We conjecture that the searching behaviors of conditioned wasps are based on the temporal and spatial neuron activity of olfactory receptor neurons and glomeruli, which are strongly correlated to the training dosages. The overall results demonstrate the utility of mathematical models for interpreting experimental observations, gaining novel insights into the dynamic behavior of classically conditioned wasps, as well as broadening the practical uses of Wasp Hound. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:596–606, 2015
A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center
Authors: Vu Khanh , Luong Nhiem V. , Hubbard Julie , Zalpour Ali , Faderl Stefan , Thomas Deborah A. , Yang Daisy , Kantarjian Hagop , Kroll Michael H.
Published: December 2014

The purpose was to determine the incidence and prevalence of venous thromboembolism (VTE) in acute leukemia patients from our institution. We conducted a retrospective study on newly diagnosed acute leukemia patients who presented at our institution from November 1999 to May 2005. Descriptive statistics and cross‐tabulation were used to describe patient characteristics. Measures of morbidity were used to address VTE risk. Chi‐square testing, Fisher's exact testing, Mann–Whitney analyses, or median testing were used to determine between‐group differences. Data analyses were conducted using Stata version 11 (Stata Corp., College Station, TX). Two hundred and ninety‐nine patients with acute lymphoblastic leukemia (ALL) and 996 patients with acute myeloid leukemia (AML) were included. After excluding patients diagnosed with VTE prior to or at the time of leukemia diagnosis, during the mean time follow‐up period of 2.5 years (range: 0.0025–10.3 years), the overall incidence rate of VTE was 3.7 per 100 person‐years: 4.2 per 100 person‐years for ALL and 3.4 per 100 person‐years for AML. Among all patients, the majority (80.6%) developed VTE within 12 months after diagnosis and during thrombocytopenia. The most common VTE was central venous catheter (CVC)‐associated upper‐extremity deep venous thrombosis. Pulmonary embolism occurred in 15% of ALL patients and 8% of AML patients. VTE recurred in 20.7% of ALL patients and 18.6% of AML patients. VTE occurs frequently in patients with acute leukemia. Studies are needed to identify risk factors for the development and recurrence of VTE among patients with acute leukemia and to establish more effective methods for preventing and treating VTEs in leukemia patients who have thrombocytopenia and/or CVC.
Chloranthones A – D: Minor and Unprecedented Dinor‐Eudesmenes from Chloranthus elatior
Authors: Liu Shu‐Ting , Xiong Juan , Tang Yu , Wang Wen‐Xuan , Bui Van‐Binh , Ma Guang‐Lei , Huang Ya , Zhao Yun , Yang Guo‐Xun , Hu Jin‐Feng
Published: December 2014

Four novel naturally occurring diastereoisomers of dinor‐eudesmenes, named chloranthones A–D (1–4, resp.), were isolated as minor components from the EtOH extract of the aerial parts of Chloranthus elatior. The unprecedented framework was established using extensive 2D‐NMR techniques. Their absolute configurations were deduced from the observed Cotton effects in their circular dichroism (CD) spectra. A plausible biosynthetic pathway to the dinor‐eudesmenes is proposed.
Sesquiterpenoids from Chloranthus henryi and Their Anti‐neuroinflammatory Activities
Authors: Wang Li‐Jun , Xiong Juan , Liu Shu‐Ting , Liu Xin‐Hua , Hu Jin‐Feng
Published: December 2014

Five new and seven known mono‐sesquiterpenoids (1–5 and 6–12, resp.) together with five known lindenane‐type disesquiterpenoids, 13–17, were isolated from the whole plant of Chloranthus henryi. Based on spectroscopic methods, the new structures were established to be (5S,6R,8S,10R)‐6‐hydroxyeudesma‐4(15),7(11)‐diene‐12,8‐olide (1), 6α‐hydroxyeudesma‐4(15),7(11),8(9)‐triene‐12,8‐olide (2), 8,12‐epoxy‐1β‐hydroxyeudesma‐4(15),7,11‐trien‐6‐one (3), 12‐oxochloraniolide A (4), and (4α)‐8‐hydroxy‐12‐norcardina‐6,8,10‐trien‐11‐one (5), respectively. Among the isolates, compound 2, zederone epoxide (8), spicachlorantin G (13), chloramultilide A (14), shizukaol B (15), and spicachlorantin B (17) showed significant anti‐neuroinflammatory effects by inhibiting nitric‐oxide (NO) production in lipopolysaccharide (LPS)‐stimulated murine BV‐2 microglial cells with relatively low cytotoxicity.
Two New Butenolides Produced by an Actinomycete Streptomyces sp.
Authors: Wang Tang , Jiang Yi , Ma Kai‐Xia , Li Yi‐Qing , Huang Rong , Xie Xiao‐Song , Wu Shao‐Hua
Published: December 2014

Two new butenolides, (4S)‐4,10‐dihydroxydodec‐2‐en‐1,4‐olide (1) and (4S)‐4,8,10‐trihydroxy‐10‐methyldodec‐2‐en‐1,4‐olide (2), together with three known compounds, MKN‐003B (3), MKN‐003C (4), and cyclo(Ala‐Leu) (5), were isolated from the culture broth of a bacterium of the genus Streptomyces derived from soil environment. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The inhibitory activities of the butenolides against eight pathogenic fungi were evaluated. All of the butenolides showed moderate‐or‐weak antifungal activities in a broth microdilution assay.
Cytotoxic Mannopyranosides of Indole Alkaloids from Zanthoxylum nitidum
Authors: Hu Jiang , Shi Xiaodong , Mao Xia , Chen Jiangang , Li Hui
Published: December 2014

Three new mannopyranosides of indole alkaloids, methyl 7‐(β‐D‐mannopyranosyloxy)‐1H‐indole‐2‐carboxylate (1), methyl 7‐[(3‐O‐acetyl‐β‐D‐mannopyranosyl)oxy]‐1H‐indole‐2‐carboxylate (2), and 2‐methyl‐1H‐indol‐7‐yl β‐D‐mannopyranoside (3), were isolated from an EtOH extract of the roots of Zanthoxylum nitidum. Their structures were identified as new compounds on the basis of the spectroscopic analyses. Bioactivity evaluation revealed that these alkaloids possess significant cytotoxicities against all the tested tumor cell lines with IC50 values of less than 30 μM.
Non‐coding RNAs: biological functions and applications
Authors: Santosh Baby , Varshney Akhil , Yadava Pramod Kumar
Published: December 2014

Analyses of the international human genome sequencing results in 2004 converged to a consensual number of ~20 000 protein‐coding genes, spanning over <2% of the total genomic sequence. Therefore, the developmental and physiological complexity of human beings remains unaccounted if viewed only in terms of the number of protein‐coding genes; the epigenetic influences involving chromatin remodelling and RNA interference and alternative precursor messenger RNA splicing of functional protein‐coding transcripts as well as post‐translational modifications of proteins increase the diversity and the functionality of the proteome and likely explain the increased complexity. In addition, there has been an explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, >90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non‐coding RNA. This review highlights the fundamental concepts of biological roles of non‐coding RNA and their importance in regulation of cellular physiology under disease conditions like cancer. Copyright © 2014 John Wiley & Sons, Ltd.
Automated Identification of Depsipeptide Natural Products by an Informatic Search Algorithm
Authors: Skinnider Michael A. , Johnston Chad W. , Zvanych Rostyslav , Magarvey Nathan A.
Published: December 2014

Nonribosomal depsipeptides are a class of potent microbial natural products, which include several clinically approved pharmaceutical agents. Genome sequencing has revealed a large number of uninvestigated natural‐product biosynthetic gene clusters. However, while novel informatic search methods to access these gene clusters have been developed to identify peptide natural products, depsipeptide detection has proven challenging. Herein, we present an improved version of our informatic search algorithm for natural products (iSNAP), which facilitates the detection of known and genetically predicted depsipeptides in complex microbial culture extracts. We validated this technology by identifying several depsipeptides from novel producers, and located a large number of novel depsipeptide gene clusters for future study. This approach highlights the value of chemoinformatic search methods for the discovery of genetically encoded metabolites by targeting specific areas of chemical space.
Base Modification Strategies to Modulate Immune Stimulation by an siRNA
Authors: Valenzuela Rachel Anne P. , Suter Scott R. , Ball‐Jones Alexi A. , Ibarra‐Soza José M. , Zheng Yuxuan , Beal Peter A.
Published: December 2014

Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi‐based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2′‐OMe or 2′‐F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence‐dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll‐like receptor 8 (TLR8) bound to small‐molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson–Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson–Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson–Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5′‐end were more effective at blocking cytokine production than those placed at the 3′‐end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance.
Expression and phosphorylation of eukaryotic translation initiation factor 4‐gamma (eIF4G) in denervated atrophic and hypertrophic mouse skeletal muscle
Authors: Fjällström Ann‐Kristin , Norrby Marlene , Tågerud Sven
Published: December 2014

The eukaryotic translation initiation factor 4‐gamma (eIF4G) is important for the initiation of protein synthesis and phosphorylation on S1108 regulates this function of eIF4G. Thus, increased phosphorylation has been reported in conditions associated with increased protein synthesis such as meal feeding and insulin/IGF‐1 treatment whereas decreased phosphorylation occurs following starvation, dexamethasone treatment, in sepsis and in atrophic denervated hind‐limb muscle. The aim of the present study was to test the hypothesis that S1108 phosphorylation of eIF4G is differentially affected in denervated atrophic hind‐limb muscles and denervated hypertrophic hemidiaphragm muscle. Protein expression and phosphorylation in innervated and 6‐days denervated atrophic hind‐limb muscles (pooled gastrocnemius and soleus) and hypertrophic hemidiaphragms were studied semi‐quantitatively using Western blots. Total expression of eIF4G did not change in denervated hind‐limb muscles but increased about 77% in denervated hemidiaphragm. S1108 phosphorylated eIF4G decreased about 64% in denervated hind‐limb muscles but increased about 1.3‐fold in denervated hemidiaphragm. The ratio of S1108 phosphorylated eIF4G to total eIF4G decreased about 60% in denervated hind‐limb muscles but no statistically significant change was observed in denervated hemidiaphragm. The differential effect of denervation on eIF4G expression and S1108 phosphorylation in hemidiaphragm (hypertrophic) and hind‐limb muscle (atrophic) may represent a regulatory mechanism that helps clarify the differential response of these muscles following denervation.
Inhibition of iron uptake by ferristatin II is exerted through internalization of DMT1 at the plasma membrane
Authors: Yanatori Izumi , Yasui Yumiko , Noguchi Yumiko , Kishi Fumio
Published: December 2014

Ferristatin II, discovered as an iron transport inhibitor, promotes the internalization and degradation of transferrin receptor 1 (TfR1). DMT1, which mediates iron transport across cell membranes, is located at the plasma membrane of enterocytes and imports dietary iron into the cytosol. TfR1 is not directly engaged in the intestinal absorption of free iron, and iron uptake by DMT1 is attenuated by ferristatin II treatment. In this study, we found another function for ferristatin II in iron uptake. Ferristatin II did not cause degradation of DMT1 but did induce DMT1 internalization from the plasma membrane. Dynasore, a small molecule inhibitor of dynamin, did not inhibit this internalization by ferristatin II, which might occur via a clathrin‐independent pathway.
The role of eNOS in the migration and proliferation of bone‐marrow derived endothelial progenitor cells and in vitro angiogenesis
Authors: Lu Aizhen , Wang Libo , Qian Liling
Published: December 2014

The role of endothelial nitric oxide synthase (eNOS) in the activities of endothelial progenitor cells (EPCs) including migration, proliferation, and tube formation in vitro was investigated. EPCs were obtained from rat bone mononuclear cells by culturing for 7–10 days in EGM‐2MV and identified by their capacity for FITC‐UEA‐1 binding and acetylated low‐density lipoprotein (Dil‐ac‐LDL) intake using fluorescence microscopy. Migration, proliferation and tube formation activities were assessed in the presence or absence of Nω‐nitro‐L‐argininemethylester (L‐NAME), an eNOS inhibitor. mRNA and protein expression of CXCR4, CXCR7, VEGFR2, and eNOS were detected by real‐time PCR and western blotting in the presence or absence of L‐NAME. Nitric oxide production was detected by nitrate reductase in the presence or absence of L‐NAME. Typical spindle‐shaped cells appeared on the 7th–10th day and confluence reached about 80%. The percentage of FITC‐UEA‐1 and Dil‐ac‐LDL double‐stained cells was about 85%. Cell migration, proliferation, and tube formation were significantly weakened after eNOS was inhibited (P < 0.05), and the expressions of CXCR4 and eNOS were significantly reduced (P < 0.05, respectively), but there was little change in CXCR7 and VEGFR2. NO production was dramatically decreased after eNOS was inhibited (P < 0.05). In summary, L‐NAME significantly reduced the expression of eNOS and NO production by EPCs and inhibited migration, proliferation and tube formation by these cells, suggesting that eNOS affects EPC activities; CXCR4 may be implicated in the action of eNOS.
IL‐21 induction of CD4+ T cell differentiation into Th17 cells contributes to bleomycin‐induced fibrosis in mice
Authors: Lei Ling , Zhong Xiao‐Ning , He Zhi‐Yi , Zhao Cheng , Sun Xue‐Jiao
Published: December 2014

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Th17 cells and interleukin‐17 (also called IL‐17A) have been found to be increased in peripheral blood and skin in patients with SSc. IL‐21 is a potent inducer of Th17 differentiation that is produced by activated T cells, and whose relationship with Th17 cells in SSc is unclear. Here, using a bleomycin (BLM)‐induced mouse model of skin fibrosis, we detected the frequency of CD4+/IL‐17+ (Th17) cells, CD4+/IL‐21+ T cells and IL‐21+ Th17 cells in peripheral blood, skin and lungs, as well as the serum content of IL‐17A and IL‐21. In addition, we assessed the differentiation of CD4+ T cells cultured from these mice into Th17 cells in response to treatment with IL‐21. Compared with the control mice, Th17 cell counts and IL‐17A levels were significantly increased and correlated with inflammatory and fibrotic indices in the skin and lungs of the BLM‐induced fibrosis mice. Moreover, serum levels of CD4+/IL‐21+ T cells, IL‐21+ Th17 cells, and IL‐21 were significantly increased in these mice, and correlated positively with serum levels of Th17 cells. In vitro experiments showed that IL‐21 treated CD4+ T cells derived from BLM‐induced mice differentiated into Th17 cells. Our results indicate that Th17 cells and IL‐17A contributes to inflammatory and fibrotic processes in the skin and lungs in a BLM‐induced mouse model of SSc. Moreover, the expansion of the Th17 cell population may be subsequent to IL‐21 promotion of the differentiation of CD4+ T cells in these mice.
Reprogramming of endometrial adult stromal cells in the presence of a ROCK inhibitor, thiazovivin, could obtain more efficient iPSCs
Authors: Mohseni Rashin , Shoae‐Hassani Alireza , Verdi Javad
Published: December 2014

Today, there is a need for a platform to efficiently generate and maintain a feeder free culture of pluripotent stem cells by small molecules or pharmacological agents. Induced pluripotent stem cell (iPSC) is considered a promising resource for restorative cell therapy in clinical areas. While fully reprogrammed iPSCs are similar to embryonic stem cells, iPSCs could be derived from the patient's own cells (autologous), which avoids the immune rejection activities. Recent advances have demonstrated that iPSCs could be generated from human fibroblasts using only four transcription factors: OCT4, SOX2, CMYC, and KLF4. However, the limitations of reprogramming technologies include low efficiency, slow kinetics, transgene integration and residual expression. Surprisingly, adult stem cells from human endometrium (endometrial stem cells; EnSCs) express OCT4 and KLF4 pluripotency factors. On the other hand, small molecule inhibitors of specific signaling pathways such as thiazovivin have been used in various aspects of iPSC generation and maintenance. Thiazovivin is a selective small molecule that directly targets Rho‐associated kinase (ROCK) and increases expression of pluripotency factors. The process using thiazovivin could be easier, faster and more cost effective than transgene integration into somatic cells. So reprogramming of OCT4 and KLF4 expressing EnSCs by a ROCK inhibitor, thiazovivin, could result in producing more efficient iPSCs compared with fibroblasts or conventional somatic cells without integration any transgene and retroviral vector.
Nickel‐Supported on La2Sn2O7 and La2Zr2O7 Pyrochlores for Methane Steam Reforming: Insight into the Difference between Tin and Zirconium in the B Site of the Compound
Authors: Ma Youhe , Wang Xiang , You Xiaojuan , Liu Jianjun , Tian Jinshu , Xu Xianglan , Peng Honggen , Liu Wenming , Li Changqing , Zhou Wufeng , Yuan Ping , Chen Xiaohong
Published: December 2014

La2Sn2O7 and La2Zr2O7, two pyrochlore compounds with different B‐site cations, were prepared and used as supports for Ni in methane steam reforming. Compared with Ni/γ‐Al2O3, both Ni/La2Zr2O7 and Ni/La2Sn2O7 show very stable reaction performance. Whereas Ni/La2Zr2O7 also displays reasonably high activity for the reaction, the activity of Ni/La2Sn2O7 is extremely low. It was found that severe coking occurred with Ni/γ‐Al2O3, but no coke formation was observed on the two pyrochlore catalysts. On the reduced and spent Ni/La2Sn2O7 catalyst, the Ni3Sn2 and Ni3Sn alloys were detected; these alloys suppressed coke formation but also decreased the activity of the catalyst. In comparison, a large amount of La2O2CO3 was formed on the used Ni/La2Zr2O7 catalyst; these species reacted with the carbon deposits formed on the Ni particles and continuously restored the Ni sites. Thus, coking was effectively suppressed and the initial high activity of the catalyst was maintained. Thus, Ni/La2Zr2O7 is a superior catalyst having the potential for industrial use.