bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboxypeptidase D is the only enzyme responsible for antibody C‐terminal lysine cleavage in Chinese hamster ovary (CHO) cells
Authors: Hu Zhilan , Zhang Henry , Haley Benjamin , Macchi Frank , Yang Feng , Misaghi Shahram , Elich Joseph , Yang Renee , Tang Yun , Joly John C. , Snedecor Bradley R. , Shen Amy 
Published: March 2016

ABSTRACTHeterogeneity of C‐terminal lysine levels often observed in therapeutic monoclonal antibodies is believed to result from the proteolysis by endogenous carboxypeptidase(s) during cell culture production. Identifying the responsible carboxypeptidase(s) for C‐terminal lysine cleavage in CHO cells would provide valuable insights for antibody production cell culture processes development and optimization. In this study, five carboxypeptidases, CpD, CpM, CpN, CpB, and CpE, were studied for message RNA (mRNA) expression by qRT‐PCR analysis in two most commonly used blank hosts (DUXB‐11 derived DHFR‐deficient DP12 host and DHFR‐positive CHOK1 host), used for therapeutic antibody production, as well an antibody‐expressing cell line derived from each host. Our results showed that CpD had the highest mRNA expression. When CpD mRNA levels were reduced by RNAi (RNA interference) technology, C‐terminal lysine levels increased, whereas there was no obvious change in C‐terminal lysine levels when a different carboxypeptidase mRNA level was knocked down suggesting that carboxypeptidase D is the main contributor for C‐terminal lysine processing. Most importantly, when CpD expression was knocked out by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, C‐terminal lysine cleavage was completely abolished in CpD knockout cells based on mass spectrometry analysis, demonstrating that CpD is the only endogenous carboxypeptidase that cleaves antibody heavy chain C‐terminal lysine in CHO cells. Hence, our work showed for the first time that the cleavage of antibody heavy chain C‐terminal lysine is solely mediated by the carboxypeptidase D in CHO cells and our finding provides one solution to eliminating C‐terminal lysine heterogeneity for therapeutic antibody production by knocking out CpD gene expression. Biotechnol. Bioeng. 2016;113: 2100–2106. © 2016 Wiley Periodicals, Inc.
Hypoxia‐responsive miR‐124 and miR‐144 reduce hypoxia‐induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1
Authors: Gu Hao , Liu Mingzhu , Ding Changmao , Wang Xin , Wang Rui , Wu Xinyu , Fan Ruitai 
Published: March 2016

AbstractCancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia‐responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR‐124 and miR‐144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3′UTR of PIM1. Functional study showed that miR‐124 or miR‐144 overexpression can inhibit hypoxia‐induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR‐124 and miR‐144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer.
Progress in Silicon Nanowire‐Based Field‐Effect Transistor Biosensors for Label‐Free Detection of DNA
Authors: Lu Na , Gao Anran , Zhou Hong , Wang Yi , Yang Xun , Wang Yuelin , Li Tie 
Published: March 2016

AbstractSilicon nanowire (SiNW), as one‐dimensional semiconducting nanomaterial, has been incorporated into the filed‐effect transistor (FET) devices to increase the efficacy and signal‐to‐noise in DNA sensing applications. Due to the advantages of high sensitivity, excellent selectivity, label‐free detection, direct electrical readout, and miniaturization, SiNW FET‐based DNA sensors have been regarded as an important tool in applications of molecular diagnostics, DNA sequencing, gene expressions, and drug discovery. Here, we review the recent progress in SiNW‐FET sensors for label‐free electrical DNA detection. We first introduce the working principle of SiNW‐FET DNA sensors, SiNW fabrication technologies, bio‐functionalization on nanowire surface, and enhancement of device sensitivity. Then we sum up the applications of SiNW sensors in detection of DNA hybridization, infectious viruses, microRNA, genetic change (DNA mutation, DNA methylation, and DNA repair), and protein‐DNA interactions. We address several crucial points of sensing performance including sensitivity, selectivity, and limit of detection. Finally, the perspectives, challenges, and some solutions of the field are also discussed.
Trifluoroethylation of Alkynes: Synthesis of Allylic‐CF3 Compounds by Visible‐Light Photocatalysis
Authors: Roh Geum‐bee , Iqbal Naeem , Cho Eun Jin 
Published: March 2016

AbstractTwo types of allylic trifluoromethylated compounds were synthesized by reacting alkynes with CF3CH2I using visible‐light photocatalysis. Subtle differences in the catalytic system controlled the selectivity of iodotrifluoroethylation and hydrotrifluoroethylation. The iodotrifluoroethylated products were obtained in the presence of [Ru(bpy)3]Cl2 and TMEDA in CH3CN under visible‐light irradiation, whereas hydrotrifluoroethylated products were synthesized using fac‐[Ir(ppy)3] and a mixture of DBU and K2CO3 in DMF. The iodotrifluoroethylation reaction worked particularly well, even at gram‐scale, and the synthetic utility of iodotrifluoroethylated products was proved by their coupling reactions, providing complex CF3‐containing products.
Experimental Study of the Carbon Deposition from CH4 onto the Ni/YSZ Anode of SOFCs
Authors: Fan P. , Zhang X. , Hua D. , Li G. 
Published: March 2016

AbstractA challenge in the operation of solid oxide fuel cells (SOFCs) with hydrocarbon fuels is the carbon deposition on the nickel/yttria‐stabilized zirconia (Ni/YSZ) anode. The Grabke‐type kinetic model has been proposed for the carbon formation based upon the assumption of elementary steps, which consist of a rate‐limiting dissociative chemisorption step and a stepwise dehydrogenation of the chemisorbed methyl group. This work experimentally studied the carbon formation on a SOFC Ni/YSZ anode exposed to CH4+H2 gas mixtures. Experiments were conducted with various gas compositions of CH4/H2 and temperatures in the range from 873 K to 1,123 K. The experimental results were used to determine a kinetic model that was applied to the SOFC operating environments. Based on the experimental data, the formula for the carbon formation rate that is dependent on the operating temperature and the gas compositions of CH4/H2 was established.
eQuIPS: eQTL Analysis Using Informed Partitioning of SNPs – A Fully Bayesian Approach
Authors: Boggis E. M. , Milo M. , Walters K. 
Published: March 2016

ABSTRACTWe develop a Bayesian multi‐SNP Markov chain Monte Carlo approach that allows published functional significance scores to objectively inform single nucleotide polymorphism (SNP) prior effect sizes in expression quantitative trait locus (eQTL) studies. We developed the Normal Gamma prior to allow the inclusion of functional information. We partition SNPs into predefined functional groups and select prior distributions that fit the group‐specific observed functional significance scores. We test our method on two simulated datasets and previously analysed human eQTL data containing validated causal SNPs. In our simulations the modified Normal Gamma always performs at least as well, and generally outperforms, the other methods considered. When analysing the human eQTL data, we placed all SNPs into their actual functional group. The ranks of the four validated causal SNPs analysed using the modified Normal Gamma increase dramatically compared to those of the other methods considered. Using our new method, three of the four validated SNPs are ranked in the top 1% of SNPs and the other is in the top 2%. For the standard Normal Gamma, the best of the other methods, the four validated SNPs had ranks in the top 1%, 4%, 20% and 59%. Crucially these substantive improvements in the ranks make it highly likely that most, if not all, of these validated SNPs would have been flagged for follow‐up using our new method, whereas at least two of them would certainly not have been using the current approaches.
Bone Material Properties in Osteogenesis Imperfecta
Authors: Bishop Nick 
Published: March 2016

ABSTRACT

Osteogenesis imperfecta entrains changes at every level in bone tissue, from the disorganization of the collagen molecules and mineral platelets within and between collagen fibrils to the macroarchitecture of the whole skeleton. Investigations using an array of sophisticated instruments at multiple scale levels have now determined many aspects of the effect of the disease on the material properties of bone tissue. The brittle nature of bone in osteogenesis imperfecta reflects both increased bone mineralization density—the quantity of mineral in relation to the quantity of matrix within a specific bone volume—and altered matrix-matrix and matrix mineral interactions. Contributions to fracture resistance at multiple scale lengths are discussed, comparing normal and brittle bone. Integrating the available information provides both a better understanding of the effect of current approaches to treatment—largely improved architecture and possibly some macroscale toughening—and indicates potential opportunities for alternative strategies that can influence fracture resistance at longer-length scales. © 2016 American Society for Bone and Mineral Research.
Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS)
Authors: Cauley Jane A , Cawthon Peggy M , Peters Katherine E , Cummings Steven R , Ensrud Kristine E , Bauer Douglas C , Taylor Brent C , Shikany James M , Hoffman Andrew R , Lane Nancy E , Kado Deborah M , Stefanick Marcia L , Orwoll Eric S ,   for the Osteoporotic Fractures in Men (MrOS) Study Research Group
Published: March 2016

ABSTRACT

Almost 30% of hip fractures occur in men; the mortality, morbidity, and loss of independence after hip fractures are greater in men than in women. To comprehensively evaluate risk factors for hip fracture in older men, we performed a prospective study of 5994 men, primarily white, age 65+ years recruited at six US clinical centers. During a mean of 8.6 years of 97% complete follow-up, 178 men experienced incident hip fractures. Information on risk factors including femoral neck bone mineral density (FNBMD) was obtained at the baseline visit. Cox proportional hazards models were used to calculate the hazard ratio (HR) with 95% confidence intervals; Fine and Gray models adjusted for competing mortality risk. Older age (≥75 years), low FNBMD, currently smoking, greater height and height loss since age 25 years, history of fracture, use of tricyclic antidepressants, history of myocardial infarction or angina, hyperthyroidism or Parkinson's disease, lower protein intake, and lower executive function were all associated with an increased hip fracture risk. Further adjustment for competing mortality attenuated HR for smoking, hyperthyroidism, and Parkinson's disease. The incidence rate of hip fracture per 1000 person-years (PY) was greatest in men with FNBMD T-scores &lt;–2.5 (white women reference database) who also had 4+ risk factors, 33.4. Men age ≥80 years with 3+ major comorbidities experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age &lt;70 years with zero comorbidities. Older men with low FNBMD, multiple risk factors, and multimorbidity have a high risk of hip fracture. Many of these assessments can easily be incorporated into routine clinical practice and may lead to improved risk stratification. © 2016 American Society for Bone and Mineral Research.
Microcin determinants are associated with B2 phylogroup of human fecal Escherichia coli isolates
Authors: Micenková Lenka , Bosák Juraj , Štaudová Barbora , Kohoutová Darina , Čejková Darina , Woznicová Vladana , Vrba Martin , Ševčíková Alena , Bureš Jan , Šmajs David 
Published: March 2016

AbstractEscherichia coli strains are classified into four main phylogenetic groups (A, B1, B2, and D) and strains of these phylogroups differ in a number of characteristics. This study tested whether human fecal E. coli isolates belonging to different phylogroups differ in prevalence of bacteriocinogenic isolates and prevalence of individual bacteriocinogenic determinants. A set of 1283 fecal E. coli isolates from patients with different diseases was tested for the presence of DNA regions allowing classification into E. coli phylogroups and for the ability to produce bacteriocins (23 colicins and 7 microcins). Of the isolates tested, the most common was phylogroup B2 (38.3%) followed by phylogroups A (28.3%), D (26.3%) and B1 (7.2%). Altogether, 695 bacteriocin producers were identified representing 54.2% of all tested isolates. The highest prevalence of bacteriocin producers was found in group B2 (60.3%) and the lowest in group B1 (44.6%). Determinants encoding colicins E1, Ia, and microcin mV were most common in phylogroup A, determinants encoding microcins mM and mH47 were most common in phylogroup B2, and determinant encoding mB17 was most common in phylogroup D. The highest prevalence of bacteriocinogeny was found in phylogroup B2, suggesting that bacteriocinogeny and especially the synthesis of microcins was associated with virulent and resident E. coli strains.
The reversed paradigm of chimerism induction: Donor conditioning with recipient‐derived bone marrow cells as a novel approach for tolerance induction in vascularized composite allotransplantation
Authors: Siemionow Maria , Rampazzo Antonio , Gharb Bahar Bassiri , Cwykiel Joanna , Klimczak Aleksandra , Madajka Maria , Nasir Serdar , Bozkurt Mehmet 
Published: March 2016

PurposeTo test a new approach of donor conditioning with recipient bone marrow cells (BMC) to induce tolerance in vascularized composite allograft (VCA) transplantation.MethodsLewis rats' (recipients) BMC were stained with PKH‐26. The ACI rats (donors) were conditioned with 80 × 106 Lewis BMC, 24 or 72 hours before VCA (groin flap) transplantation. Forty‐eight VCA were performed between ACI donors and Lewis recipients. In groups I and II, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received 7‐day anti‐αβ‐TCR/cyclosporine‐A post‐transplantation. In groups III and IV, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received no systemic immunosuppression. In group V, recipients received 7‐day anti‐αβ‐TCR/cyclosporine‐A post‐transplantation. In group VI, recipients received no systemic immunosuppression. Assessment included evaluation of transplant viability and induction of donor‐specific chimerism via flow cytometry, immunofluorescence, and PCR.ResultsGroups III, IV, and VI rejected allografts, at an average of 14 ± 5.2, 10 ± 2.7, and 8 ± 0.7 days. In groups I, II, and V, the mean survival was 80 ± 18.2 (p = 0.0002), 64 ± 27.4 (p = 0.001), and 30 ± 4.7 (p = 0.02) days. In groups I and II, donor‐specific chimerism in the blood decreased from 8.8 ± 3.4% and 8.6 ± 3.4% on day 7 to 3.7 ± 1.32% (p = 0.02) and 4.7 ± 2.7% when the flaps manifested grade 3 rejection. The presence of PKH‐26+ Lewis BMC was confirmed in the donor's blood, bone marrow, lymphoid organs, and liver (preconditioned at 24 and 72 hours).ConclusionsDonor preconditioning is a novel approach modifying recipient's responsiveness to donor allograft and prolonging the allograft survival under short‐term immunosuppression. © 2015 Wiley Periodicals, Inc. Microsurgery 36:676–683, 2016.
The developmental expression of the CDK inhibitor p57kip2 (Cdkn1c) in the early mouse placenta
Authors: Saunders Ann Catherine Eugenia , McGonnigal Bethany , Uzun Alper , Padbury James 
Published: March 2016

SUMMARYp57kip2 (encoded by the Cdkn1c gene) is a member of the cip/kip family of cyclin‐dependent kinase inhibitors that mediates cell cycle arrest in G1, allowing cells to differentiate. In the placenta, p57kip2 is involved in endoreduplication, formation of trophoblast giant cells, trophoblast invasion, and expansion of placental cell layers. Here, we quantitatively and qualitatively define the cell‐ and region‐specific expression of mouse placental p57kip2 using laser‐capture microdissection, in situ hybridization, and immunohistochemistry. Cdkn1c RNA was quantified by real‐time quantitative PCR. Co‐expression of Pl1 was used to identify trophoblast giant cells while Tbpba was used to identify spongiotrophoblast cells. Timed sacrifices were also carried out at embryonic days E7.5, E8.5, E9.5, and E12.5 to profile the expression in embryos and their placentas. At E8.5, intense expression of Cdkn1c was seen in invasive TGCs and the ectoplacental cone. Cdkn1c expression was more diffuse and more abundant in the labyrinth that in the junctional zone at both E9.5 and E12.5. Immunohistochemistry revealed robust p57kip2 staining in trophoblast giant cells and in the ectoplacental cone at E8.5. p57kip2 protein was seen in giant cells and throughout the labyrinth, although its abundance was reduced in the junctional zone at E9.5, and became more diffuse by E12.5. The early and intense expression in trophoblast giant cells is consistent with a role for p57kip2 in the invasive phenotype of these cells. Mol. Reprod. Dev. 83: 405–412, 2016. © 2016 Wiley Periodicals, Inc.
General descriptions of follower forces derived via a geometrically exact inverse contact algorithm
Authors: Konyukhov Alexander 
Published: March 2016

SummaryThe main feature of the geometrically exact theory of contact is that all objects, which are necessary for computation, weak form and residual, linearized weak form, and tangent matrices are given in a covariant closed form in the local coordinate system corresponding to the geometry of contact pairs. This allows easily to construct computational algorithms for the normal and tangential follower forces as an inverse contact algorithm. In this case, following the definition of the follower forces as given and not changing in the local coordinate system, we have to modify all objects for the contact taking into account the definition of follower forces instead of constitutive relationships for the contact interfaces. The main feature is that the tangent matrices for both normal and tangential part being split into the rotational and the curvature parts are symmetric for any order of approximation. The following numerical examples are selected in the current article to illustrate the effectiveness of implementation: (1) the modeling of a pure bending with a moment applied either as a pair of single forces or a distributed follower forces (pressure) in both 2D and 3D cases; (2) modeling of inflation of a plate as application of the distributed follower normal forces (pressure); and (3) modeling of twisting of a beam with the rectangular cross‐section as application of the tangential follower forces algorithm. Copyright © 2016 John Wiley & Sons, Ltd.
Public and Private Production in a Mixed Delivery System: Regulation, Competition and Costs
Authors: Bel Germà , Rosell Jordi 
Published: March 2016

AbstractAcademics and policymakers are increasingly shifting the debate concerning the best form of public service provision beyond the traditional dilemma between pure public and pure private delivery modes, because, among other reasons, there is a growing body of evidence that casts doubt on the existence of systematic cost savings from privatization, while any competition seems to be eroded over time. In this paper, we compare the relative merits of public and private delivery within a mixed delivery system. We study the role played by ownership, transaction costs, and competition on local public service delivery within the same jurisdiction. Using a stochastic cost frontier, we analyze the public‐private urban bus system in the Barcelona Metropolitan Area. We find that private firms have higher delivery costs than those incurred by the public firm, especially when transaction costs are taken into account. Furthermore, tenders tend to decrease delivery costs.
Short‐term effectiveness of a web‐based tailored intervention for cancer survivors on quality of life, anxiety, depression, and fatigue: randomized controlled trial
Authors: Willems Roy A. , Bolman Catherine A. W. , Mesters Ilse , Kanera Iris M. , Beaulen Audrey A. J. M. , Lechner Lilian 
Published: March 2016

AbstractBackgroundThe aim of this study was to evaluate the short‐term effectiveness of the web‐based computer‐tailored intervention Kanker Nazorg Wijzer (Cancer Aftercare Guide). The intervention aims to support cancer survivors with managing psychosocial and lifestyle‐related issues. In this study, the impact on quality of life, anxiety, depression, and fatigue were evaluated.MethodsCancer survivors were recruited through 21 Dutch hospitals (November 2013–June 2014). Outcome measures included quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30), anxiety and depression (Hospital Anxiety and Depression Scale), and fatigue (Checklist Individual Strength). In a randomized controlled trial with an intervention group (n = 231) and a waiting list control group (n = 231), the short‐term effectiveness was evaluated through multilevel linear regression analyses, controlling for selective dropout, baseline differences, and several demographic and disease‐related characteristics.ResultsIn total, 188 participants of the intervention group and 221 of the control group completed the 6‐month measurement (dropout = 11.5%). The intervention was effective in reducing depression (B = −0.63, p = 0.007, f2 = 0.019, d = 0.21) and fatigue (B = −4.36, p = 0.020, f2 = 0.013, d = 0.21). In addition, effects were found for emotional (B = 3.47, p = 0.022, f2 = 0.013, d = 0.15) and social functioning (B = 3.95, p = 0.011, f2 = 0.017, d = 0.15), although this evidence was less strong. There were indications that the effects of fatigue and social functioning were influenced by module use.ConclusionsWhile effect sizes were small, they can be considered as clinically relevant. With the Cancer Aftercare Guide being an effective, low‐intensive, and easy accessible intervention, it could serve as a first step in stepped care for needs assessment and initial support for psychosocial problems that are present after cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Robotic surgery rapidly and successfully implemented in a high volume laparoscopic center on living kidney donation
Authors: Janki S. , Klop K. W. J. , Hagen S. M. , Terkivatan T. , Betjes M. G. H. , Tran T. C. K. , Ijzermans J. N. M. 
Published: March 2016

AbstractBackgroundIt is important to minimize risks associated with live donor nephrectomy. In this study we evaluated the results of left‐sided robot‐assisted donor nephrectomies in comparison with standard techniques.MethodsData on perioperative results, kidney function, and recipient and graft survival were collected. All left‐sided laparoscopic and hand‐assisted procedures were selected as control groups.ResultsFifty‐nine robot‐assisted procedures were performed by two surgeons. Operative time was significantly longer in the robot‐assisted group compared with both control groups. However, it decreased significantly during procedures 40–59 compared with procedures 20–39 (P = 0.014) to median 172.5 (114.0–242.0) min. One conversion to the open approach occurred in the robot group due to a bleeding of the renal artery stump. No difference was found between all techniques at 3 months post‐donation.ConclusionLeft‐sided robot‐assisted donor nephrectomy is feasible with over time a significant decrease in operative time with good outcomes for donor and recipient. Copyright © 2016 John Wiley & Sons, Ltd.