bluuebunny/crossref_metadata_2025_split huggingface dataset:
An allosteric antibody to the leptin receptor reduces body weight and reverses the diabetic phenotype in the Lepob/Lepob mouse
Authors: Bhaskar Vinay , Goldfine Ira D. , Gerstner Resi , Michelson Kristen , Tran Catarina , Nonet Genevieve , Bohmann David , Pongo Elizabeth , Zhao Jingsong , Horwitz Arnold H. , Takeuchi Toshihiko , White Mark , Corbin John A. 
Published: June 2016

ObjectiveLeptin (LEP) deficiency results in major metabolic perturbations, including obesity, dyslipidemia, and diabetes. Although LEP deficiency can be treated with daily injections of a recombinant LEP, generation of an antibody activating the LEP receptor (LEPR) that has both an intrinsically long half‐life and low immunogenicity could be useful in the treatment of this condition.MethodsPhage display technology coupled with flow cytometry and cell‐based in vitro assays were employed to identify an allosteric agonist of the mouse LEPR. LEP‐deficient Lepob/Lepob mice were used to compare in vivo effects of LEP to antibody administration. To evaluate hypothalamic effects of treatment, changes in mRNA levels of neuropeptide Y and proopiomelanocortin were measured.ResultsXPA.80.037 is a monoclonal antibody that demonstrates allosteric agonism of the mouse LEPR. Treatment of Lepob/Lepob mice with XPA.80.037 markedly reduced hyperphagia and body weight, normalized blood glucose and plasma insulin levels, and corrected dyslipidemia. These metabolic alterations correlated with changes in mRNA levels of neuropeptide Y and proopiomelanocortin, suggesting that XPA.80.037 had hypothalamic effects.ConclusionsAgonist allosteric monoclonal antibodies to the LEPR can correct metabolic effects associated with LEP deficiency in vivo and thereby have the potential to treat conditions of LEP deficiency.
How Do Nonprofits Respond to Regulatory Thresholds: Evidence From New York's Audit Requirements
Authors: St. Clair Travis 
Published: June 2016

AbstractNonprofits in the United States must comply with various state and federal regulations to maintain their tax‐exempt status. Despite persistent calls to increase accountability in the nonprofit sector, there is little research examining the burden imposed by existing regulatory requirements, especially at the state level. This paper uses a bunching design to estimate the avoidance behavior exhibited by tax‐exempt charities in response to New York State's audit requirements. There is clear evidence of bunching in response to the requirement that nonprofits above certain revenue thresholds file financial statements reviewed by or audited by an independent certified public accountant. Measuring the extent of bunching around the revenue notches yields estimates of the average revenue that nonprofits either forego or fail to report in avoidance of the requirements. Results from dynamic estimation show that charities near the threshold for a review engagement report approximately $1,300 less revenue than otherwise predicted by a counterfactual; charities near the threshold for a full audit report approximately $1,400 less. The results have implications for the optimal design of state‐level financial regulations.
Predictors of health‐related quality of life over time among pediatric hematopoietic stem cell transplant recipients
Authors: Loiselle Kristin A. , Rausch Joseph R. , Bidwell Sarah , Drake Sarah , Davies Stella M. , Pai Ahna L. H. 
Published: June 2016

AbstractBackgroundAdvances in hematopoietic stem cell transplantation (HSCT) have contributed to increased survival for pediatric patients. However, there are inconsistent findings regarding the impact of HSCT on health‐related quality of life (HRQOL) outcomes for children. This study aimed to establish trajectories of HRQOL following HSCT and identify predictors of the HRQOL course.ProcedureNinety caregivers of a child who received HSCT (mean age = 6.42 years) for various oncologic, immunologic, and metabolic conditions completed questionnaires regarding family psychosocial functioning and child HRQOL at the time of discharge from HSCT and follow‐up HRQOL at four additional time points.ResultsThere was a significant change in overall HRQOL in 3 months postdischarge, with the greatest improvement in physical functioning. Caregiver stress and social support, and child psychosocial problems predicted changes in HRQOL over time.ConclusionsThese results point to potentially modifiable factors that are related to the course of HRQOL following HSCT, and interventions aimed at these factors should be implemented.
Outcome of young children with high‐grade glioma treated with irradiation‐avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials
Authors: Espinoza Juan C , Haley Kelley , Patel Neha , Dhall Girish , Gardner Sharon , Allen Jeffrey , Torkildson Joseph , Cornelius Albert , Rassekh Rod , Bedros Antranik , Etzl Morris , Garvin James , Pradhan Kamnesh , Corbett Robin , Sullivan Michael , McGowage Geoffrey , Stein Dagmar , Jasty Rama , Sands Stephen A. , Ji Lingyun , Sposto Richard , Finlay Jonathan L. 
Published: June 2016

AbstractPurposeTo report the final analysis of survival outcomes for children with newly diagnosed high‐grade glioma (HGG) treated on the “Head Start” (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old.Patients and MethodsBetween 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients. Patients with predominantly brainstem tumors were excluded. Patients were to be treated with single induction chemotherapy regimen C, comprising four cycles of vincristine, carboplatin, and temozolomide. Following induction, patients underwent marrow‐ablative chemotherapy and autologous hematopoietic cell rescue. Irradiation was used for patients with residual tumor after consolidation or >6 years old or at the time of tumor progression.ResultsThe 5‐year event‐free survival (EFS) and overall survival (OS) for all HGG patients were 25 ± 8% and 36 ± 9%, respectively. The EFS at 5 years for patients with AA and GBM were 24 ± 11% and 30 ± 16%, respectively (P = 0.65). The OS at 5 years for patients with AA and GBM was 34 ± 12% and 35 ± 16%, respectively (P = 0.83). Children <36 months old experienced improved 5‐year EFS and OS of 44 ± 17% and 63 ± 17%, compared with children 36–71 months old (31 ± 13% and 38 ± 14%) and children >72 months old (0% and 13 ± 12%).ConclusionsIrradiation‐avoiding treatment strategies should be evaluated further in young children with HGG given similar survival rates to older children receiving standard irradiation‐containing therapies.
Mechanical and thermomechanical properties of PLA/Man‐made cellulose green composites modified with functional chain extenders—A comprehensive study
Authors: Jaszkiewicz A. , Meljon A. , Bledzki A.K. 
Published: June 2016

The present study aims to investigate the influence of functional chain extenders on the mechanical and thermomechanical behavior of fully bio‐based polylactide composites reinforced with man‐made cellulose short fibers. Two additives with epoxy and maleic anhydride functionalities were used for this purpose. The biocomposite modifications resulted in a considerably altered fiber–matrix interface, which was clearly visible in SEM images, and which affected the tensile and flexural characteristics of the investigated materials. In particular, the chain extender functionalized with maleic anhydride groups influenced the fiber–matrix bonding, and contributed to pull‐outs when the biocomposite fractured. Moreover, a dynamic mechanical thermal analysis was performed, and the storage modulus E′, loss modulus E″, and loss factor (tan δ) were determined. Also, the heat deflection and Vicat softening temperatures were verified. The results of the comprehensive thermal analysis confirmed that the reinforcement of amorphous PLA has no physical effect on its thermal stability. POLYM. COMPOS., 39:1716–1723, 2018. © 2016 Society of Plastics Engineers
N‐Oligo(3‐hydroxybutyrate)‐functionalized polypyrroles: towards bio‐erodible conducting copolymers
Authors: Domagala Anna , Domagala Wojciech , Ledwon Przemyslaw , Musiol Marta , Janeczek Henryk , Stolarczyk Agnieszka , Kurcok Piotr , Adamus Grazyna , Lapkowski Mieczyslaw 
Published: June 2016

AbstractNew copolymer materials have been prepared by chemical grafting of oligomeric 3‐hydroxybutyric acid (OHB) onto polypyrrole (PPy) derivatives. The influence of grafting density and molecular weight of OHB brushes on the physicochemical properties of prepared copolymers was investigated. PPy substrates were prepared by FeCl3‐driven oxidative homopolymerization of N‐(2‐carboxyethyl)pyrrole or its copolymerization with pyrrole. The grafting method employed involved controlled anionic polymerization of β‐butyrolactone on pyrrole‐tethered potassium carboxylate active sites. Obtained PPy‐g‐OHB copolymers of varying grafting density and pendant polyester chain length were characterized and the observed structure–property relationships discussed. The impact of real time exposure to phosphate‐buffered saline environment was investigated and the residue products were characterized. Cross‐correlation of spectroscopic, thermal, electrical and elemental analysis data afforded comprehensive evaluation of the structure of prepared materials and their behaviour in hydrolytic medium. Erosion and degradation pathways have been identified, indicating ways to consciously tailor the physicochemical properties of these new biomimetic materials. © 2016 Society of Chemical Industry
Evaluation of two convection‐permitting ensemble systems in the HyMeX Special Observation Period (SOP1) framework
Authors: Nuissier O. , Marsigli C. , Vincendon B. , Hally A. , Bouttier F. , Montani A. , Paccagnella T. 
Published: June 2016

This study compares and evaluates two convection‐permitting ensemble systems based on Consortium for Small‐scale Modeling (COSMO) and Applications of Research to Operations at Mesoscale (AROME) models in the HyMeX framework. The performance of both AROME‐EPS and COSMO‐H2‐EPS (where EPS denotes Ensemble Prediction System) is assessed over the whole HyMeX special observation period SOP1. Afterwards, an analysis of the predictability of two heavy precipitation events observed during the intense observation period IOP16a of the first HyMeX special observation period SOP1 on 26 October 2012 is also undertaken. Ensemble discharge forecasts were carried out to reinforce the quantitative precipitation forecast evaluation.A probabilistic evaluation is conducted over a 53 day period of the HyMeX SOP1. AROME‐EPS has a more discriminating behaviour than COSMO‐H2‐EPS, especially when comparing both ensembles over a verification domain including a strong variability in precipitation events. AROME‐EPS still has slightly better reliability, but the statistical resolution is nearly the same for both convection‐permitting ensemble prediction systems (CPEPS).For the specific case of heavy precipitation occurring over the Var region (southeastern France), the fine‐scale surface precipitation prediction is strongly sensitive to the good behaviour of a surface low pressure simulated by the ensembles, focusing strong low‐level moisture towards Var. The convergence between strong moistened southerly low‐level inflow and northerly cold air blowing from the Po Valley is a key factor controlling the predictability of the heavy precipitation episode over the Liguria region (northwestern Italy). The two convection‐permitting ensembles, though different in their characteristics, exhibit a good amount of probabilistic skill in forecasting heavy precipitation at a relatively high spatial and temporal resolution. Therefore they can be regarded as promising tools for operational forecasts.
Synthesis and Characterization of Cadmium (II), Lead (II), and Indium (III) Ketoacidoximate Complexes and their Conversion to Metal Oxides
Authors: Khanderi Jayaprakash , Davaasuren Bambar , Rothenberger Alexander 
Published: June 2016

AbstractThe reaction of Cd(II), Pb(II), and In(III) salts with in situ generated pyruvic acid oxime (ketoacidoximate) of the type [O2C‐C(R)=NOH]‐, (R=CH3 or ‐CH2‐C6H5) results in five novel complexes [Cd{O2C‐C(CH2‐C6H5)=NOH}2(py)2]2 (py=C5H5N) 1, [Cd{O2C‐C(CH2‐C6H5)=NOH}2(im)2]2 (im=C3H4N2) 2, [Pb{O2C‐C(CH3)=NOH}2(py)]2 3, [Pb{O2C‐C(CH2‐C6H5)=NOH}2(dmso)]2 (dmso=dimethyl sulfoxide) 4 and (NH4)[In{O2C‐C(CH3)=NOH}4] 5. Single crystal X‐ray structure determination of 1–5 reveal mono‐nuclear In(III) and di‐nuclear, µ2‐oxo bridged Cd(II), Pb(II) complexes. 1–5 undergo thermal decomposition below 210ºC to the corresponding metal oxides.
An Oxido‐Bridged Diiron(II) Complex as Functional Model of Catechol Dioxygenase
Authors: Dey Dhananjay , De Abhranil , Yadav Hare Ram , Guin Partha Sarathi , Choudhury Angshuman Roy , Kole Niranjan , Biswas Bhaskar 
Published: June 2016

AbstractAn oxido‐bridged diiron(II)‐phenanthroline complex, [Fe2O(phen)2Cl2] (1) [phen =1,10‐phenanthroline] has been synthesized from an oxido‐bridged diiron(III) precursor in presence of sodium azide and structurally characterized by different spectroscopic tools including single crystal X‐ray diffraction study.From X‐ray crystal structure of 1, it is revealed that each of the Fe(II) centre is in distorted octahedral geometry with FeN4OCl core and the molecule crystallizes in Pnc2 space group. Bond valence sum (BVS) calculation confirms the existence of iron ions in +2 oxidation state in 1. The diiron(II) complex has been evaluated as model system for the catechol dioxygenase enzyme by using 3,5‐di‐tert‐butylcatechol (DTBC) as the substrate in acetonitrile medium, revealing that 1 efficiently mimics the catalytic cycle of catechol dioxygenase. Upon stoichiometric addition of DTBC pretreated with two equivalents of triethylamine (Et3N) to the diiron complex, two catecholate‐to‐iron(III) LMCT bands (515 nm and 734 nm) are observed. The in situgenerated catecholate adduct from 1in acetonitrile solution react with dioxygen to afford exclusively extradiol cleavage products along with a small amount of benzoquinone, which is also discerned from the appearance and decrease in intensity of the electronic spectral bands around (708 nm; 507 nm) nm. Nucleophilic attack by molecular oxygen on catecholate adduct in solution provides substantial evidence for the regioselective extradiol cleavage products.
A CuI‐Phosphonotriazolate Coordination Polymer Based on [CuI4Cl] Cluster for Fluorescent Sensing of O2
Authors: Wang Dianpeng , Zhang Weiquan , Sun Jinyu , Ling Yun , Chen Zhenxia , Zhou Yaming 
Published: June 2016

AbstractA novel cuprous coordination polymer built of [Cu4ICl] cluster and 4‐(1,2,4‐triazol‐4‐yl)phenylphosphonate acid (H2ptz) ligand has been hydrothermally synthesized, in which the CuI is in‐situ generated by the reduction reaction from CuII precursors. This compound shows a green fluorescent emission with a maximum peak at 510 nm under N2 flow in solid state, which can be turned off by 21 % O2 flow in minutes. Interestingly, it can be turned on again by switching to N2 flow. A possible mechanism has also been proposed.
Fibrinogen Induces RUNX2 Activity and Osteogenic Development from Human Pluripotent Stem Cells
Authors: Kidwai Fahad , Edwards Jessica , Zou Li , Kaufman Dan S. 
Published: June 2016

Abstract
Pluripotent stem cells, both human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC), provide an important resource to produce specialized cells such as osteogenic cells for therapeutic applications such as repair or replacement of injured, diseased or damaged bone. hESCs and iPSCs can also be used to better define basic cellular and genetic mechanisms that regulate the earliest stages of human bone development. However, current strategies to mediate osteogenic differentiation of hESC and iPSC are typically limited by the use of xenogeneic components such as fetal bovine serum (FBS) that make defining specific agents that mediate human osteogenesis difficult. Runt-related transcription factor 2 (RUNX2) is a key regulator required for osteogenic differentiation. Here, we used a RUNX2-YFP reporter system to characterize the novel ability of fibrinogen to mediate human osteogenic development from hESC and iPSC in defined (serum-free) conditions. These studies demonstrate that fibrinogen mediates significant osteo-induction potential. Specifically, fibrinogen binds to the surface integrin (α9β1) to mediate RUNX2 gene expression through the SMAD1/5/8 signaling pathway. Additional studies characterize the fibrinogen-induced hESC/iPSC-derived osteogenic cells to demonstrate these osteogenic cells retain the capacity to express typical mature osteoblastic markers. Together, these studies define a novel fibrinogen-α9β1-SMAD1/5/8-RUNX2 signaling axis can efficiently induce osteogenic differentiation from hESCs and iPSCs. Stem Cells 2016;34:2079–2089
Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference
Authors: Yao Wei , Lay Yu-An Evan , Kot Alexander , Liu Ruiwu , Zhang Hongliang , Chen Haiyan , Lam Kit , Lane Nancy E. 
Published: June 2016

AbstractMesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 μg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 x 105, IV) or ADSC + LLP2A-Ale.In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent.There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration.
CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-Cell Adhesion
Authors: Liu Jie , Qi Yanmei , Li Shaohua , Hsu Shu-Chan , Saadat Siavash , Hsu June , Rahimi Saum A. , Lee Leonard Y. , Yan Chenghui , Tian Xiaoxiang , Han Yanling 
Published: June 2016

Abstract
Understanding the regulation of cell-cell interactions during the formation of compact myocardial structures is important for achieving true cardiac regeneration through enhancing the integration of stem cell-derived cardiomyocytes into the recipient myocardium. In this study, we found that cellular repressor of E1A-stimulated genes 1 (CREG1) is highly expressed in both embryonic and adult hearts. Gain- and loss-of-function analyses demonstrated that CREG1 is required for differentiation of mouse embryonic stem (ES) cell into cardiomyocytes and the formation of cohesive myocardium-like structures in a cell-autonomous fashion. Furthermore, CREG1 directly interacts with Sec8 of the exocyst complex, which tethers vesicles to the plasma membrane. Site-directed mutagenesis and rescue of CREG1 knockout ES cells showed that CREG1 binding to Sec8 is required for cardiomyocyte differentiation and cohesion. Mechanistically, CREG1, Sec8, and N-cadherin colocalize at intercalated discs in vivo and are enriched at cell-cell junctions in cultured cardiomyocytes. CREG1 overexpression enhances the assembly of adherens and gap junctions. By contrast, its knockout inhibits the Sec8-N-cadherin interaction and induces their degradation. These results suggest that the CREG1 binding to Sec8 enhances the assembly of intercellular junctions and promotes cardiomyogenesis.
Transforming growth factor-β-Expressing Mesenchymal Stem Cells Induce Local Tolerance in a Rat Liver Transplantation Model of Acute Rejection
Authors: Tang Jincao , Yang Renjie , Lv Ling , Yao Aihua , Pu Liyong , Yin Aihong , Li Xiangcheng , Yu Yue , Nyberg Scott L. , Wang Xuehao 
Published: June 2016

Abstract
Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-β)-overexpressing mesenchymal stem cells (MSCs) in inducing a local immunosuppression in liver grafts after transplantation. MSCs were transduced with a lentiviral vector expressing the human TGF-β1 gene; TGF-β1-overexpressing MSCs (designated as TGF/MSCs) were then transfused into the liver grafts via the portal vein of a rat LT model of acute rejection. Rejection severity was assessed by clinical and histologic analysis. The immunity suppression effects and mechanism of TGF/MSCs were tested, focusing on their ability to induce generation of regulatory T cells (Tregs) in the liver grafts. Our findings demonstrate that transfusion of TGF/MSCs prevented rejection, reduced mortality, and improved survival of rats after LT. The therapeutic effects were associated with the immunosuppressive effects of MSCs and TGF-β1. Their reciprocal effects on Tregs induction and function resulted in more CD4 + Foxp3 + Helios- induced Tregs, fewer Th17 cells, and improved immunosuppressive effects in local liver grafts. Thus, TGF/MSCs can induce a local immunosuppressive effect in liver grafts after transplantation. The immunomodulatory activity of TGF-β1 modified MSCs may be a gateway to new therapeutic approaches to prevent organ rejection in clinical transplantation.
Generation of Induced Cardiospheres via Reprogramming of Skin Fibroblasts for Myocardial Regeneration
Authors: Xu Jian-Yong , Lee Yee-Ki , Ran Xinru , Liao Song-Yan , Yang Jiayin , Au Ka-Wing , Lai Wing-Hon , Esteban Miguel A. , Tse Hung-Fat 
Published: June 2016

AbstractRecent pre-clinical and clinical studies have suggested that endogenous cardiospheres (eCS) are potentially safe and effective for cardiac regeneration following myocardial infarction (MI). Nevertheless the preparation of autologous eCS requires invasive myocardial biopsy with limited yield. We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from mouse adult skin fibroblasts treated with Gsk3β inhibitor-(2′Z,3′E)- 6-Bromoindirubin-3′-oxime and Oncostatin M. They resembled eCS, but contained a higher percentage of cells expressing Mesp1, Isl1, and Nkx2.5. They were differentiated into functional cardiomyocytes in vitro with similar electrophysiological properties, calcium transient and contractile function to eCS and mouse embryonic stem cell-derived cardiomyocytes. Transplantation of iCS (1 × 106 cells) into mouse myocardium following MI had similar effects to transplantation of eCS but significantly better than saline or fibroblast in improving left ventricular ejection fraction, increasing anterior/septal ventricular wall thickness and capillary density in the infarcted region 4 weeks after transplantation. No tumor formation was observed. iCS generated from adult skin fibroblasts by somatic reprogramming and a cocktail of Gsk3β inhibitor-6-Bromoindirubin-3′-oxime and Oncostatin M may represent a novel source for cell therapy in MI.