bluuebunny/crossref_metadata_2025 huggingface dataset:
Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease
Authors: Mak Ki M. , Mei Rena
Published: February 2017

Basement membranes provide structural support to epithelium, endothelium, muscles, fat cells, Schwann cells, and axons. Basement membranes are multifunctional: they modulate cellular behavior, regulate organogenesis, promote tissue repair, form a barrier to filtration and tumor metastasis, bind growth factors, and mediate angiogenesis. All basement membranes contain type IV collagen (Col IV), laminin, nidogen, and perlecan. Col IV and laminin self‐assemble into two independent supramolecular networks that are linked to nidogen and perlecan to form a morphological discernable basement membrane/basal lamina. The triple helical region, 7S domain and NCI domain of Col IV, laminin and laminin fragment P1 have been evaluated as noninvasive fibrosis biomarkers of alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease. Elevated serum Col IV and laminin are related to degrees of fibrosis and severity of hepatitis, and may reflect hepatic basement membrane metabolism. But the serum assays have not been linked to disclosing the anatomical sites and lobular distribution of perisinusoidal basement membrane formation in the liver. Hepatic sinusoids normally lack a basement membrane, although Col IV is a normal matrix component of the space of Disse. In liver disease, laminin deposits in the space of Disse and codistributes with Col IV, forming a perisinusoidal basement membrane. Concomitantly, the sinusoidal endothelium loses its fenestrae and is transformed into vascular type endothelium. These changes lead to capillarization of hepatic sinusoids, a significant pathology that impairs hepatic function. Accordingly, codistribution of Col IV and laminin serves as histochemical marker of perisinusoidal basement membrane formation in liver disease. Anat Rec, 300:1371–1390, 2017. © 2017 Wiley Periodicals, Inc.
Active Disturbance Rejection in Affine Nonlinear Systems Based on Equivalent‐Input‐Disturbance Approach
Authors: Gao Fang , Wu Min , She Jinhua , Cao Weihua
Published: February 2017

This paper presents a disturbance rejection method for an affine nonlinear system. The control system is constructed based on the equivalent‐input‐disturbance (EID) approach. An affine nonlinear state observer is used to reconstruct the state of the affine nonlinear system and to estimate an EID. The well‐known differential mean value theorem enables us to describe the closed‐loop system in the state space as a linear‐parameter‐varying system. This makes it easy to derive sufficient conditions of global uniform ultimate boundedness in term of linear matrix inequalities (LMIs) by using a Lyapunov function and convexity theory. Controllers are designed based on the LMIs. A numerical example is used to illustrate the design of the control system. And a comparison between the EID‐based control and the sliding‐mode control demonstrates the effectiveness and advantages of the EID‐based control method.
Equilibrium response to carbon dioxide and aerosol forcing changes in a 1D air–sea interactive model
Authors: Wang Xiaocong , Feng Juan
Published: February 2017

A 1D air–sea interactive model that couples an atmospheric column model with a slab ocean model was introduced. The model simulated an exact balance between radiative cooling and convective heating in the free troposphere. Within the planet boundary layer, the turbulent mixing produces cooling in the upper part and warming in the lower part, which is compensated by radiative and convective heating together. The model was then used to explore the equilibrium response of sea surface temperature (SST) and precipitation to carbon dioxide (CO2) and aerosol forcing changes. Results show a warming or cooling signal owning to increased CO2 or aerosols can be well captured by the ocean, leading to an increasing or decreasing of the SST, and hence the precipitation. Cutting off the interactions between atmosphere and ocean however renders different results. By applying the relaxed weak temperature gradient (WTG) approximation, the local response to aerosol forcing perturbations was investigated, which was shown to be largely different from the global response in spite of the same forcing. To understand the nonlinear interactions among different forcings, the equilibrium responses to multiple combinations of CO2 and aerosol forcings are analyzed.
KIC011764567: An evolved Kepler‐star showing substantial flare activity
Authors: Kitze M. , Akopian A. A. , Hambaryan V. , Torres G. , Neuhäuser R.
Published: February 2017

We intensively studied the flare activity on the stellar object KIC011764567. The star was thought to be a solar type, with a temperature of Teff≈(5640±200) K, log(g) = (4.3 ± 0.3) dex, and a rotational period of Prot≈22 days. High‐resolution spectra turn the target to an evolved object with Teff=(5300±150) K, a metalicity of [m/H] =(−0.5±0.2), a surface gravity of log(g) = (3.3 ± 0.4) dex, and a projected rotational velocity of v sin i = (22 ± 1) km s−1. Within an observing time span of 4 years, we detected 150 flares in Kepler data in the energy range 1036–1037 erg. From a dynamical Lomb–Scargle periodogram, we have evidence for differential rotation as well as for stellar spot evolution and migration. On analyzing the occurrence times of the flares, we found hints for a periodic flare frequency cycle of 430–460 days, a significant increase with an increase in threshold of the flares' equivalent duration. One explanation is a very short activity cycle of the star with that period. Another possibility, also proposed by others in similar cases, is that the larger flares may be triggered by external phenomena, such as magnetic interaction with an unseen companion. Our high‐resolution spectra show that KIC011764567 is not a short‐period binary star.
“The legacy of thalidomide” ‐ A multidisciplinary meeting held at the University of York, United Kingdom, on September 30, 2016
Authors: Newbronner Elizabeth , Vargesson Neil , Atkin Karl
Published: February 2017

Background

Between 1957 and 1962 thalidomide was used as a nonaddictive, nonbarbiturate sedative that also was successful in relieving the symptoms of morning sickness in early pregnancy. Infamously, thousands of babies were subsequently born with severe birth defects. The drug is used again, today, to successfully treat leprosy, and tragically, there is a new generation of thalidomide damaged children in Brazil. While the outward damage in babies has been documented, the effects of the damage upon the survivors as they grow up, the lifestyle changes and adaptations required to be made, as well as studies into ageing in survivors, has received little attention and remains understudied.

Methods

A unique multidisciplinary meeting was organized at the University of York bringing together thalidomide survivors, clinicians, scientists, historians, and social scientists to discuss the past, the current and the future implications of thalidomide.

Results

There is still much to learn from thalidomide, from its complex history and ongoing impact on peoples' lives today, to understanding its mechanism/s to aid future drug safety, to help identify new drugs retaining clinical benefit without the risk of causing embryopathy.

Conclusion

For thalidomide survivors, the original impairments caused by the drug are compounded by the consequences of a lifetime of living with a rare disability, and early onset age‐related health problems. This has profound implications for their quality of life and need for health and social care services. It is vital that these issues are addressed in research, and in clinical practice if thalidomide survivors are to “age well”. Birth Defects Research 109:296–299, 2017. © 2017 Wiley Periodicals, Inc.
An evaluation of a caregiver training protocol on the generalization and maintenance of successful pediatric feeding interventions
Authors: Aclan Megan D. , Taylor Rachel S.
Published: February 2017

Previous researchers have documented the positive effects achieved by trained clinicians providing behavioral interventions for pediatric feeding disorders; however, few have evaluated the maintenance of those treatments when subsequently implemented by primary caregivers. Further, the majority of previous caregiver training research has relied on the use of multicomponent training packages making it difficult to determine which components are necessary for success. The purpose of the current investigation was to evaluate the effects of instructions and feedback on caregivers' implementation of feeding protocols in a home setting. Results of the current study suggest that feedback may be the most effective training component in training packages designed to teach caregivers to implement an effective feeding protocol. Potential concomitant changes in child behavior are also discussed.
Evaluation of an arm‐splint belt to reduce self‐injury
Authors: Morgan Andrew C. , Wilder David A. , Podlesnik Christopher A. , Kelley Michael E.
Published: February 2017

After a functional analysis yielded undifferentiated results, a subsequent assessment suggested self‐injury exhibited by a young boy with autism was sensitive to physical restraint. Canvas arm splints with metal stays were initially effective to reduce self‐injury. Although we successfully faded the number of stays in each sleeve to 3, self‐injury reemerged. We then used a withdrawal design to evaluate a behind‐the‐back belt connected to the arm splints. When the belt and splints were on, self‐injury did not occur. When the belt was removed, self‐injury increased, even though the splints remained intact. Finally, we faded the length of the belt to allow increased range of motion, and rates of self‐injury remained low.
Sol–gel synthesis and luminescence property of Sr4Al2O7:Re3+,R+ (Re = Eu and Dy; R = Li, Na and K) phosphors for white LEDs
Authors: Zhang Wentao , Yu Meng , Dai Siyi , Chen Xianfei , Long Jianping
Published: February 2017

Sr4Al2O7:Eu3+ and Sr4Al2O7:Dy3+ phosphors with alkali metal substitution were prepared using a sol–gel method. The effects of a charge compensator R on the structure and luminescence of Sr4Al2O7:Re3+,R+ (Re = Eu and Dy; R = Li, Na and K) phosphors were investigated in detail. Upon heating to 1400°C, the structure of the prepared samples was that of the standard phase of Sr4Al2O7. Under ultraviolet excitation, all Sr4Al2O7:Eu3+,R+ samples exhibited several narrow emission peaks ranging from 550 to 700 nm due to the 4f → 4f transition of Eu3+ ions. All Sr4Al2O7:Dy3+,R+ phosphors showed two emission peaks at 492 and 582 nm, due to the 4F9/2 → 6H15/2 and 4F9/2 → 6H13/2 transitions of Dy3+ ions, respectively. The luminescence intensity of Sr4Al2O7:Re3+,R+ (Re = Eu and Dy; R = Li, Na and K) phosphors improved markedly upon the addition of charge compensators, promoting their application in white light‐emitting diodes with a near‐ultraviolet chip.
Bone morphogenetic protein‐7 (BMP‐7) augments insulin sensitivity in mice with type II diabetes mellitus by potentiating PI3K/AKT pathway
Authors: Chattopadhyay Tandrika , Singh Rajiv Ranjan , Gupta Sarika , Surolia Avadhesha
Published: February 2017

A direct link between development of insulin resistance and the presence of chronic inflammation, in case of obesity exists, with cytokines playing an important role in glucose metabolism. Members of TGF‐β superfamily, including bone morphogenetic proteins (BMPs), have been shown to be involved in islet morphogenesis, establishment of β‐cell mass and adipose cell fate determination. Here, we demonstrate a novel and direct role of BMP‐4 and ‐7 in the regulation of glucose homeostasis and insulin resistance. An age‐dependent increase in serum BMP‐4 and decrease in serum BMP‐7 levels was observed in animal models of type II diabetes. In this study, BMP‐7 and ‐4 have been demonstrated to have antagonistic effects on insulin signaling and thereby on glucose homeostasis. BMP‐7 augmented glucose uptake in the insulin sensitive tissues such as the adipose and muscle by increasing Glut4 translocation to the plasma membrane through phosphorylation and activation of PDK1 and Akt, and phosphorylation and translocation of FoxO1 to the cytoplasm in liver/HepG2 cells. Restoration of BMP‐7 levels in serum of diabetic animals resulted in decreased blood glucose levels in contrast to age matched untreated control groups, opening up a new therapeutic avenue for diabetes. On the contrary, BMP‐4 inhibited insulin signaling through activation of PKC‐θ isoform, and resulted in insulin resistance through the attenuation of insulin signaling. BMP‐7 therefore is an attractive candidate for tackling a multifaceted disease such as diabetes, since it not only reduces body fat, but also strengthens insulin signaling, causing improved glucose uptake and ameliorating peripheral insulin resistance. © 2017 BioFactors, 43(2):195–209, 2017
Chronic transgenerational vitamin B12 deficiency of severe and moderate magnitudes modulates adiposity—probable underlying mechanisms
Authors: Ghosh Shampa , Sinha Jitendra Kumar , Muralikrishna Bojanapalli , Putcha Uday Kumar , Raghunath Manchala
Published: February 2017

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12‐restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12‐restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch‐up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400–414, 2017
Plasmid‐encoded biosynthetic genes alleviate metabolic disadvantages while increasing glucose conversion to shikimate in an engineered Escherichia coli strain
Authors: Rodriguez Alberto , Martínez Juan A. , Millard Pierre , Gosset Guillermo , Portais Jean‐Charles , Létisse Fabien , Bolivar Francisco
Published: February 2017

Metabolic engineering strategies applied over the last two decades to produce shikimate (SA) in Escherichia coli have resulted in a battery of strains bearing many expression systems. However, the effects that these systems have on the host physiology and how they impact the production of SA are still not well understood. In this work we utilized an engineered E. coli strain to determine the consequences of carrying a vector that promotes SA production from glucose with a high‐yield but that is also expected to impose a significant cellular burden. Kinetic comparisons in fermentors showed that instead of exerting a negative effect, the sole presence of the plasmid increased glucose consumption without diminishing the growth rate. By constitutively expressing a biosynthetic operon from this vector, the more active glycolytic metabolism was exploited to redirect intermediates toward the production of SA, which further increased the glucose consumption rate and avoided excess acetate production. Fluxomics and metabolomics experiments revealed a global remodeling of the carbon and energy metabolism in the production strain, where the increased SA production reduced the carbon available for oxidative and fermentative pathways. Moreover, the results showed that the production of SA relies on a specific setup of the pentose phosphate pathway, where both its oxidative and non‐oxidative branches are strongly activated to supply erythrose‐4‐phosphate and balance the NADPH requirements. This work improves our understanding of the metabolic reorganization observed in E. coli in response to the plasmid‐based expression of the SA biosynthetic pathway. Biotechnol. Bioeng. 2017;114: 1319–1330. © 2017 Wiley Periodicals, Inc.
A novel Bxb1 integrase RMCE system for high fidelity site‐specific integration of mAb expression cassette in CHO Cells
Authors: Inniss Mara C. , Bandara Kalpanie , Jusiak Barbara , Lu Timothy K. , Weiss Ron , Wroblewska Liliana , Zhang Lin
Published: February 2017

As CHO cell line development for biotherapeutic production becomes more sophisticated through the availability of the CHO genome sequence, the ability to accurately and reproducibly engineer the host cell genome has become increasingly important. Multiple well characterized systems for site‐specific integration will enable more complex cell line engineering to generate cell lines with desirable attributes. We built and characterized a novel recombinase mediated cassette exchange (RMCE) system using Bxb1 integrase and compared it to the commonly used Flp/FRT RMCE system. We first integrated a DNA construct flanked by either Bxb1 attachment sites or FRT sequences (referred to as a landing pad) into the Fer1L4 genomic locus of CHO‐S cells using CRISPR/Cas9 mediated homologous recombination. We characterized the resulting clones harboring either the Bxb1 or Flp/FRT landing pad using whole genome resequencing to compare their genomes with the parental host cell line. We determined that each landing pad was specifically integrated into the Fer1L4 locus in the selected clones and observed no major structural changes in the genome or variations in copy number as a result of CRISPR/Cas9 modification. We subsequently tested the ability of the Bxb1 and Flp/FRT landing pad clones to perform proper RMCE with donor vectors containing identical mAb expression cassettes flanked by either Bxb1 attachment sites or FRT sites. We demonstrated that both RMCE systems were able to generate stable pools in a similar time frame with comparable mAb expression. Through genetic characterization of up to 24 clones derived from either system, we determined that the BxB1 RMCE system yielded higher fidelity RMCE events than the Flp/FRT system as evidenced by a higher percentage of clones with expected integration of the mAb cassette into the landing pad in the respective cell lines. We conclude that Bxb1 RMCE is an excellent alternative to Flp/FRT RMCE and valuable addition to our toolbox enabling the engineering of more sophisticated cell lines for biotherapeutic production. Biotechnol. Bioeng. 2017;114: 1837–1846. © 2017 Wiley Periodicals, Inc.
Kinetic Study on Solvolysis of 2‐Methylfuran‐3‐carbonyl Chloride in Binary Solvent Mixtures
Authors: Choi Hojune , Yang Kiyull , Koh Han Joong , Koo In Sun
Published: February 2017

Rate constants for solvolysis of 2‐methylfuran‐3‐carbonyl chloride (1) in ethanol, methanol, and aqueous binary mixtures incorporating ethanol, methanol, acetone, 2,2,2‐trifluoroethanol, and 1,1,1,3,3,3‐hexafluoro‐2‐propanol are reported. The 34 solvents give an extended Grunwald–Winstein correlation with l = 0.26 ± 0.05, m = 0.71 ± 0.04, and correlation coefficient R2 = 0.963. Activation parameters calculated from the rate constants measured at three different temperatures in five different solvents are presented. In the deuterated methanol, a solvent kinetic isotope effect of 1.15 was observed at 0°C. The kinetic features observed indicate that the reaction proceeds through an SN1 mechanism with a little SN2 character. The reactivity–selectivity principle is also followed in alcohol‐water mixtures.
Selection of DNA Aptamers Against Botulinum Neurotoxin E for Development of Fluorescent Aptasensor
Authors: Ren Shuo , Shin Hye‐Soo , Gedi Vinayakumar , Dua Pooja , Lee Dong‐Ki , Kim Soyoun
Published: February 2017

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are the deadliest toxins known to mankind with a potential of possible bioterrorism agents. Due to the high‐potential harm of these toxins, a sensitive and real‐time monitoring capable detection systems are required for the early stage detection. In this study, a novel sol–gel‐based SELEX was used to isolate single‐stranded nucleic acids (ssDNA) aptamers against purified BoNT type E toxoid (BoNTE) using a chemically synthesized random N40 ssDNA library. The bound aptamer sequences after five rounds were analyzed using next‐generation sequencing and the resulted high‐frequency aptamers were characterized using biolayer interferometry. Among the tested, aptamer BT5.6 showed low nanomolar binding affinity (KD, 53.3 nM) toward BoNTE. As a proof of concept, the aptamer was utilized in a graphene oxide‐based detection platform. In summary, we screened and identified a ssDNA aptamer with high affinity toward BoNTE, which, we believe can be used for development of sensitive detection systems.
Development and validation of a high‐throughput online solid‐phase extraction–liquid chromatography–tandem mass spectrometry method for the detection of gonyautoxins 1&4 and gonyautoxins 2&3 in human urine
Authors: Coleman Rebecca , Lemire Sharon W. , Bragg William , Garrett Alaine , Ojeda‐Torres Geovannie , Wharton Rebekah , Hamelin Elizabeth , Thomas Jerry , Johnson Rudolph C.
Published: February 2017

Paralytic shellfish toxins (PSTs), including gonyautoxins and saxitoxins, are produced by multiple species of microalgae and dinoflagellates, and are bioaccumulated by shellfish and other animals. Human exposure to PSTs typically occurs through ingestion of recreationally harvested contaminated shellfish and results in nonspecific symptomology. Confirmation of exposure to PSTs has often relied on the measurement of saxitoxin, the most toxic congener; however, gonyautoxins (GTXs), the sulfated carbamate derivatives of saxitoxin, may be present in shellfish at higher concentrations. To improve identification of PST exposures, our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography method to identify GTX1–4 in human urine with tandem mass spectrometry. The reportable range varied for each analyte, with all falling within 0.899 and 250 ng/mL in urine with precision <15% and >85% accuracy as determined for all quality control samples. This new online method quantitates GTX1–4 following exposures to PSTs, supporting the work of public health authorities.
An easy to use open source authoring tool to create effective and reusable learning objects
Authors: Gordillo Aldo , Barra Enrique , Quemada Juan
Published: February 2017

Authoring tools play a crucial role in the development of learning content facilitating the creation of Learning Objects. However, not much work has been done in order to determine if educators actually can use these tools to create effective and reusable Learning Objects in an easy way. This paper address this issue by presenting and evaluating an open source authoring tool called ViSH Editor. Three factors were evaluated: the usability and user acceptance of the authoring tool, the quality and learning effectiveness of the created Learning Objects, and the reusability of these resources. Usability was evaluated through a lab test and the user acceptance with a survey among 180 users. Quality evaluation was conducted using LORI (Learning Object Review Instrument). The learning effectiveness was evaluated through learner surveys and test scores. Finally, reusability was evaluated by using the LORI instrument, by measuring metadata quality using a set of metrics, and by a quantitative analysis of reuse. Results show that ViSH Editor is an authoring tool capable of allowing educators to create effective and reusable Learning Objects in an easy way. © 2017 Wiley Periodicals, Inc. Comput Appl Eng Educ 25:188–199, 2017; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21789
Xanthomonas citri pv. citri Pathotypes: LPS Structure and Function as Microbe‐Associated Molecular Patterns
Authors: Di Lorenzo Flaviana , Silipo Alba , Andersen Gersby Lotte Bettina , Palmigiano Angelo , Lanzetta Rosa , Garozzo Domenico , Boyer Claudine , Pruvost Olivier , Newman Mari‐Anne , Molinaro Antonio
Published: February 2017

Xanthomonas citri pv. citri is the pathogen responsible for Asiatic citrus canker, one of the most serious citrus diseases worldwide. The lipopolysaccharide (LPS) molecule has been demonstrated to be involved in X. citri pv. citri virulence. Despite enormous progress in investigations of the molecular mechanisms for bacterial pathogenicity, determination of the detailed LPS structure–activity relationship is limited, as the current knowledge is mainly based on structural determination of one X. citri pv. citri strain. As X. citri pv. citri strains are distinguished into three main pathogenicity groups, we characterized the full structure of the LPS from two pathotypes that differ in their host‐range specificity. This revealed an intriguing difference in LPS O‐chain structure. We also tested the LPSs and isolated lipid A moieties for their ability to act as microbe‐associated molecular patterns in Arabidopsis thaliana. Both LPS/lipid As induced ROS accumulation, but no difference was observed between the two pathotypes.
A Novel Class of Natural FXR Modulators with a Unique Mode of Selective Co‐regulator Assembly
Authors: Zheng Weili , Lu Yi , Lin Shengchen , Wang Rui , Qiu Lin , Zhu Yanlin , Yao Benqiang , Guo Fusheng , Jin Shikai , Jin Lihua , Li Yong
Published: February 2017

The farnesoid X receptor (FXR) is an important target for drug discovery. Small molecules induce a conformational change in FXR that modulates its binding to co‐regulators, thus resulting in distinct FXR functional profiles. However, the mechanisms for selectively recruiting co‐regulators by FXR remain elusive, partly because of the lack of FXR‐selective modulators. We report the identification of two natural terpenoids, tschimgine and feroline, as novel FXR modulators. Remarkably, their crystal structures uncovered a secondary binding pocket important for ligand binding. Further, tschimgine or feroline induced dynamic conformational changes in the activation function 2 (AF‐2) surface, thus leading to differential co‐regulator recruiting profiles, modulated by both hydrophobic and selective hydrogen‐bond interactions unique to specific co‐regulators. Our findings thus provide a novel structure template for optimization for FXR‐selective modulators of clinical value.
Untargeted metabolomics analysis of adipogenic transformation in OP9‐DL1 cells using liquid chromatography‐mass spectrometry: Implications for thymic adipogenesis
Authors: Tan Jianxin , Wang Yajun , Wang Siliang , Zhang Nannan , Wu Simeng , Yuan Zhe , Zhu Xike
Published: February 2017

Adipocyte deposition is a key feature of age‐related thymic involution, but the underlying mechanisms responsible for thymic adiposity remain to be elucidated. In the present study, we utilized rosiglitazone, a potent peroxisome proliferator‐activated receptor γ agonist, to induce adipogenic differentiation of OP9‐DL1 cells, and detected the metabolomics alterations during adipogenic differentiation by using liquid chromatography‐mass spectrometry. The obtained metabolites were further processed by multivariate statistical analysis, including principal component analysis, partial least squares discriminant analysis, and orthogonal projection on latent‐structures discriminant analysis. As a result, we identified a total of 33 significantly differential metabolites between dimethyl sulphoxide‐ and rosiglitazone‐treated OP9‐DL1 cells, which were closely related to the dysregulation of phospholipid metabolism pathway, oxidative stress, and associated amino acid metabolism. Meanwhile, two pathways including glycerophospholipid metabolism and nitrogen metabolism were significantly perturbed (P < 0.05). Collectively, our results may provide some heuristic guidance for addressing the underlying mechanism of thymic adipogenesis, and future studies are warranted to unravel the functions of these altered metabolites in thymic adipogenesis.
Thrombotic valvular dysfunction with transcatheter mitral interventions for postsurgical failures
Authors: Eng Marvin H. , Greenbaum Adam , Wang Dee Dee , Wyman Janet , DNP  , Arjomand Heider , Yadav Pradeep , Nemeh Hassan , Paone Gaetano , Guerrero Mayra , O'Neill William
Published: February 2017

Background

Degenerated surgical mitral valve repairs or surgical prostheses are currently being treated with transcatheter mitral valve replacement (TMVR). We report the procedural and mid‐term assessment of thirteen cases.

Methods

From 12/2013 to 12/2015, 13 consecutive patients with degenerated mitral valve repair or valve replacement were treated. Patients were assessed for mitral valve academic valve consortium (MVARC) defined outcomes.

Results

Immediate procedural MVARC defined technical success was 92%. At 30 days MVARC device and procedure success were 61% and 84%, respectively. Mean follow‐up was 150 days [IQR 40–123 days]. There were 2 late major adverse outcomes, a noncardiac related death (628 days) and a stroke (382 days). The mean mitral gradient decreased from 9.5 ± 3.4 to 5.5 ± 2.6 mm Hg (P < 0.01). Three patients were found to have high gradients, two presented with heart failure while another patient was found to have reduced leaflet motion and abnormal thickening postprocedure. The two patients with heart failure were treated with enoxaparin, which caused subsequent resolution of increased valve gradients in one patient. The other patient could not tolerate prolonged treatment from anticoagulation due to gastrointestinal bleeding. Three of 13 patients were treated with dual‐antiplatelet therapy and were suspected to have valve thrombosis.

Conclusion

Thrombotic related dysfunction post‐TMVR occurred in 15% (2/13) of patients and one patient had abnormal leaflet thickening that may have been thrombus related. Dual‐antiplatelet therapy was used in all 3 cases suggesting the possible need for oral anticoagulation postmitral valve‐in‐valve therapy. © 2017 Wiley Periodicals, Inc.
Comparing the Relative Reactivities of Food and Vitamin Molecules Toward Electrochemically Generated Superoxide in Dimethylformamide
Authors: Lauw Sherman J. L. , Yeo Joyce Y. H. , Chiang Zhong , Webster Richard D.
Published: February 2017

Superoxide (O2.−), an anionic radical of the reactive oxygen species (ROS) family, is continuously produced in the body and can lead to the undesirable modification and damage of important biological molecules. In the present study, the relative reactivities of 18 food and vitamin molecules toward electrochemically generated O2.− were investigated in N,N‐dimethylformamide (DMF) solutions by using cyclic voltammetry (CV). The quenching of O2.− was measured by monitoring the decreases in the anodic currents of the reverse peaks after the one‐electron reduction of molecular oxygen (O2), while systematically increasing the concentration of the test substrates. The reactivity of each compound was then approximated and compared using effective concentration indexes, EC10 and EC50, which represent the amount of compound required to reduce the concentration of the electrochemically generated O2.− by 10 and 50%, respectively, under the present conditions. Where possible, the likely mechanisms that are involved in the scavenging of O2.− are also discussed.
Online diagnostics of time‐varying nonlinear chemical processes using moving window kernel principal component analysis and Fisher discriminant analysis
Authors: Galiaskarov M. R. , Kurkina V. V. , Rusinov L. A.
Published: February 2017

A combined method of diagnostics is proposed for a class of nonlinear multivariate processes where fast and slow faults are observed with essentially different rates of their development. Because fast faults occur against the background of the slow ones and have many common symptoms, the process turns out nonstationary. That is why it is proposed to use kernel principal component analysis with a moving window for monitoring purposes. The faults are identified with Fisher discriminant analysis started up when the fault is detected, and through some moments it is blocked to reduce blurring of classes. The efficiency of the method is demonstrated by the example of diagnostics of hydrocarbon pyrolysis process.
The effect of data matrix augmentation and constraints in extended multivariate curve resolution–alternating least squares
Authors: Olivieri Alejandro C. , Tauler Romà
Published: February 2017

The reliability of results obtained by multivariate curve resolution (MCR) methods is strongly dependent on the absence or presence of a small degree of rotational ambiguity associated to them. In this work, the effect of rotational ambiguities on the profiles resolved by MCR methods is examined in detail for cases of interest to analytical chemistry, where a number of calibration samples are usually prepared containing analyte standards, while test samples may contain additional uncalibrated constituents. These multiple chemical data sets having common constituents are simultaneously analyzed using matrix augmentation strategies. In these cases, conditions for better resolution and improved profiles are more easily achieved. To evaluate the extension of rotational ambiguities and to quantify their reduction after matrix augmentation, we applied the MCR‐BANDS procedure. Results obtained by the application of this procedure confirmed that the simultaneous analysis of multiple data sets decreased considerably the extension of rotational ambiguities compared with those obtained when only a single data set is analyzed. Simulated and experimental data sets of interest to second‐order analytical calibration are discussed.
Noncovalent Interactions and Internal Dynamics in Pyridine–Ammonia: A Combined Quantum‐Chemical and Microwave Spectroscopy Study
Authors: Spada Lorenzo , Tasinato Nicola , Vazart Fanny , Barone Vincenzo , Caminati Walther , Puzzarini Cristina
Published: February 2017

The 1:1 complex of ammonia with pyridine is characterized by using state‐of‐the‐art quantum‐chemical computations combined with pulsed‐jet Fourier‐transform microwave spectroscopy. The computed potential energy landscape indicates the formation of a stable σ‐type complex, which is confirmed experimentally: analysis of the rotational spectrum shows the presence of only one 1:1 pyridine–ammonia adduct. Each rotational transition is split into several components owing to the internal rotation of NH3 around its C3 axis and to the hyperfine structure of both 14N quadrupolar nuclei, thus providing unequivocal proof that the two molecules form a σ‐type complex involving both a N−H⋅⋅⋅N and a C−H⋅⋅⋅N hydrogen bond. The dissociation energy (BSSE‐ and ZPE‐corrected) is estimated to be 11.5 kJ mol−1. This work represents the first application of an accurate yet efficient computational scheme, designed for the investigation of small biomolecules, to a molecular cluster.
Are Evidence Standards Different for Genomic‐ vs. Clinical‐Based Precision Medicine? A Quantitative Analysis of Individualized Warfarin Therapy
Authors: Dhanda DS , Guzauskas GF , Carlson JJ , Basu A , Veenstra DL
Published: February 2017

Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics: value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic vs. amiodarone‐warfarin drug–drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research. Over the past decade, the EVPI for the pharmacogenomic strategy decreased from $1,550 to $140 vs. $1,220 to $280 per patient for the drug‐interaction strategy. Evidence levels thus appear to be higher for pharmacogenomic‐guided vs. drug‐interaction‐guided warfarin dosing. Clinical guidelines and reimbursement policies for warfarin PM could be informed by these findings.
Phenotypic Characterization of Trisomy 12 Monoclonal B‐Cell Lymphocytosis
Authors: Sorigue Marc , Maluquer Clara , Junca Jordi
Published: February 2017

Background

Trisomy 12 chronic lymphocytic leukemia (CLL) is phenotypically different from the rest of CLL cytogenetic subgroups. However, it is unknown whether this is also the case for trisomy 12 CLL‐phenotype monoclonal B‐cell lymphocytosis (MBL).

Methods

We analyzed the expression of several markers in a series of 89 cytogenetically characterized MBL (including 17 trisomy 12 cases). Additionally, we compared the expression of these markers between trisomy 12 MBL, trisomy 12 CLL and a series of cases with trisomy 12 but fulfilling only 3 of the 5 Moreau CLL diagnostic criteria.

Results

CD20, CD22 and CD79b were expressed more intensely in trisomy 12 MBL than in non‐trisomy 12 MBL and there was a trend towards a dimmer expression of CD43 in trisomy 12 MBL. There were no differences between trisomy 12 CLL and trisomy 12 MBL. Expression of CD20 was dimmer and that of CD43 brighter in trisomy 12 MBL than in cases with trisomy 12 and 3 Moreau criteria.

Conclusions

In this study, trisomy 12 and non‐trisomy 12 MBL were phenotypically different, but the differences are similar to those described between trisomy 12 and non‐trisomy 12 CLL, suggesting that they are a distinct subgroup within CLL, given that the differences can already be found at its precursor stage. © 2017 International Clinical Cytometry Society
Fine‐needle aspiration findings of Xp11 translocation renal cell carcinoma metastatic to a hilar lymph node
Authors: El Naili Reima , Nicolas Marlo , Gorena Amanda , Policarpio‐Nicolas Maria Luisa C.
Published: February 2017

Xp11 translocation renal cell carcinoma (RCC) is a specific type of renal cell carcinoma recently placed under the “MiT family translocation RCC” at the last 2013 ISUP Vancouver classification of renal neoplasia. This tumor contains variable proportions of clear cells and could easily mimic papillary RCC, clear cell type, and clear cell papillary RCC. Given the small number of published cytologic findings of this tumor, it could easily present as a diagnostic pitfall. We describe a case of a 23‐year‐old man with a history of prior nephrectomy who presented with multiple mediastinal lymphadenopathies on imaging surveillance follow‐up. Fine‐needle aspiration of the lymph node showed tumor cells with voluminous clear to eosinophilic cytoplasm, well‐defined cell borders and hyperchromatic nuclei arranged in papillary architecture. Review of the prior nephrectomy specimen showed papillary cores surrounded by cells with voluminous clear to finely granular eosinophilic cytoplasm and distinct cell borders. Immunohistochemical stains performed on the nephrectomy specimen showed tumor positivity for CD10, E‐cadherin, a‐methylacyl coenzyme A racemase, and TFE3 supporting the diagnosis of Xp11 translocation renal cell carcinoma. Although this tumor was initially described predominantly in children, it could also occur in adults, as seen in this case. Familiarity with the cytologic findings of this tumor, use of immunohistochemical stains, or cytogenetic test to determine the type of gene fusion will be extremely useful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:456–462. © 2017 Wiley Periodicals, Inc.
Granulocyte colony‐stimulating factor‐producing pancreatic anaplastic carcinoma in ascitic fluid at initial diagnosis: A case report
Authors: Kubota Nao , Naito Yoshiki , Kawahara Akihiko , Taira Tomoki , Yamaguchi Tomohiko , Yoshida Tomoko , Abe Hideyuki , Takase Yorihiko , Fukumitsu Chihiro , Murata Kazuya , Ishida Yusuke , Okabe Yoshinobu , Kimura Yoshizo , Tanigawa Masahiko , Mihara Yutaro , Nakayama Masamichi , Yamaguchi Rin , Akiba Jun , Yano Hirohisa
Published: February 2017

Granulocyte colony‐stimulating factor (G‐CSF)‐producing pancreatic tumors are extremely rare. These tumors have an aggressive clinical course and no established treatment. Here, we report an autopsy case of G‐CSF‐production in pancreatic anaplastic carcinoma (PAC). A 72‐year‐old woman presented with a large pancreatic head mass and multiple liver metastases. Laboratory data showed leukocytosis (leukocyte count 113.3 × 103/µL) and high serum G‐CSF levels (441 pg/mL; normal range: <39.0 pg/mL). The ascitic fluid was submitted to our pathology laboratory at initial diagnosis. Cytopathology showed that smears from the ascitic fluid were highly cellular and contained numerous malignant cells, mainly in loose groupings. Occasional pseudoglandular formations and giant cells were also present. The malignant cells were round, and no spindle‐shaped cells were visible. The nuclei were round to ovoid with coarsely granular chromatin and large prominent nucleoli. Upon immunocytochemistry, tumor cells were positive for G‐CSF and vimentin; there was no E‐cadherin expression. Histopathological examination of the tumor showed a mixed composition of adenocarcinomatous and sarcomatous regions. Upon immunohistochemistry, both components were positive for G‐CSF. Few CD34‐positive myeloblasts were observed in the bone marrow. Thus, we diagnosed this as a case of G‐CSF production in PAC with leukocytosis. To the best of our knowledge, this is the first report on G‐CSF expression immunocytochemically confirmed in PAC. Diagn. Cytopathol. 2017;45:463–467. © 2017 Wiley Periodicals, Inc.
An SSR‐based approach incorporating a novel algorithm for identification of rare maize genotypes facilitates criteria for landrace conservation in Mexico
Authors: Hayano‐Kanashiro Corina , Martínez de la Vega Octavio , Reyes‐Valdés M. Humberto , Pons‐Hernández José‐Luis , Hernández‐Godinez Fernando , Alfaro‐Laguna Emigdia , Herrera‐Ayala José Luis , Vega‐Sánchez Ma. Cristina , Carrera‐Valtierra José Alfredo , Simpson June
Published: February 2017

As maize was domesticated in Mexico around 9,000 years ago, local farmers have selected and maintained seed stocks with particular traits and adapted to local conditions. In the present day, many of these landraces are still cultivated; however, increased urbanization and migration from rural areas implies a risk that this invaluable maize germplasm may be lost. In order to implement an efficient mechanism of conservation in situ, the diversity of these landrace populations must be estimated. Development of a method to select the minimum number of samples that would include the maximum number of alleles and identify germplasm harboring rare combinations of particular alleles will also safeguard the efficient ex‐situ conservation of this germplasm. To reach this goal, a strategy based on SSR analysis and a novel algorithm to define a minimum collection and rare genotypes using landrace populations from Puebla State, Mexico, was developed as a “proof of concept” for methodology that could be extended to all maize landrace populations in Mexico and eventually to other native crops. The SSR‐based strategy using bulked DNA samples allows rapid processing of large numbers of samples and can be set up in most laboratories equipped for basic molecular biology. Therefore, continuous monitoring of landrace populations locally could easily be carried out. This methodology can now be applied to support incentives for small farmers for the in situ conservation of these traditional cultivars.
Environmental control of the microfaunal community structure in tropical bromeliads
Authors: Kratina Pavel , Petermann Jana S. , Marino Nicholas A. C. , MacDonald Andrew A. M. , Srivastava Diane S.
Published: February 2017

Ecological communities hosted within phytotelmata (plant compartments filled with water) provide an excellent opportunity to test ecological theory and to advance our understanding of how local and global environmental changes affect ecosystems. However, insights from bromeliad phytotelmata communities are currently limited by scarce accounts of microfauna assemblages, even though these assemblages are critical in transferring, recycling, and releasing nutrients in these model ecosystems. Here, we analyzed natural microfaunal communities in leaf compartments of 43 bromeliads to identify the key environmental filters underlying their community structures. We found that microfaunal community richness and abundance were negatively related to canopy openness and vertical height above the ground. These associations were primarily driven by the composition of amoebae and flagellate assemblages and indicate the importance of bottom‐up control of microfauna in bromeliads. Taxonomic richness of all functional groups followed a unimodal relationship with water temperature, peaking at 23–25°C and declining below and above this relatively narrow thermal range. This suggests that relatively small changes in water temperature under expected future climate warming may alter taxonomic richness and ecological structure of these communities. Our findings improve the understanding of this unstudied but crucial component of bromeliad ecosystems and reveal important environmental filters that likely contribute to overall bromeliad community structure and function.
Association between matrix metalloproteinase‐9 and worsening heart failure events in patients with chronic heart failure
Authors: Morishita Tetsuji , Uzui Hiroyasu , Mitsuke Yasuhiko , Amaya Naoki , Kaseno Kenichi , Ishida Kentaro , Fukuoka Yoshitomo , Ikeda Hiroyuki , Tama Naoki , Yamazaki Taketoshi , Lee Jong‐Dae , Tada Hiroshi
Published: February 2017

Aims

Matrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF.

Methods and results

Plasma levels of MMP‐9, TIMP‐1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow‐up (median 109 months). MMP‐9 and TIMP‐1 levels and the MMP‐9/TIMP‐1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP‐9 than those without HF events (P = 0.004). Kaplan–Meier analysis demonstrated a higher probability of HF events with high MMP‐9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP‐9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03–13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20–11.02; P = 0.023) among patients with high MMP‐9 values compared with patients with low BNP and low MMP‐9 values.

Conclusions

MMP‐9 and TIMP‐1 levels correlate with the severity of chronic HF. MMP‐9 is a strong predictor of HF events, suggesting that a disparity between MMP‐9 and TIMP‐1 levels and increased MMP‐9 levels may help predict HF events.