bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of human N‐ and T‐type calcium channels by an ortho‐phenoxyanilide derivative, MONIRO‐1
Authors: McArthur Jeffrey R , Motin Leonid , Gleeson Ellen C , Spiller Sandro , Lewis Richard J , Duggan Peter J , Tuck Kellie L , Adams David J 
Published: June 2017

Background and PurposeVoltage‐gated calcium channels are involved in nociception in the CNS and in the periphery. N‐type (Cav2.2) and T‐type (Cav3.1, Cav3.2 and Cav3.3) voltage‐gated calcium channels are particularly important in studying and treating pain and epilepsy.Experimental ApproachIn this study, whole‐cell patch clamp electrophysiology was used to assess the potency and mechanism of action of a novel ortho‐phenoxylanilide derivative, MONIRO‐1, against a panel of voltage‐gated calcium channels including Cav1.2, Cav1.3, Cav2.1, Cav2.2, Cav2.3, Cav3.1, Cav3.2 and Cav3.3.Key ResultsMONIRO‐1 was 5‐ to 20‐fold more potent at inhibiting human T‐type calcium channels, hCav3.1, hCav3.2 and hCav3.3 (IC50: 3.3 ± 0.3, 1.7 ± 0.1 and 7.2 ± 0.3 μM, respectively) than N‐type calcium channel, hCav2.2 (IC50: 34.0 ± 3.6 μM). It interacted with L‐type calcium channels Cav1.2 and Cav1.3 with significantly lower potency (IC50 > 100 μM) and did not inhibit hCav2.1 or hCav2.3 channels at concentrations as high as 100 μM. State‐ and use‐dependent inhibition of hCav2.2 channels was observed, whereas stronger inhibition occurred at high stimulation frequencies for hCav3.1 channels suggesting a different mode of action between these two channels.Conclusions and ImplicationsSelectivity, potency, reversibility and multi‐modal effects distinguish MONIRO‐1 from other low MW inhibitors acting on Cav channels involved in pain and/or epilepsy pathways. High‐frequency firing increased the affinity for MONIRO‐1 for both hCav2.2 and hCav3.1 channels. Such Cav channel modulators have potential clinical use in the treatment of epilepsies, neuropathic pain and other nociceptive pathophysiologies.Linked ArticlesThis article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
Easy Generation of Facial Animation Using Motion Graphs
Authors: Serra J. , Cetinaslan O. , Ravikumar S. , Orvalho V. , Cosker D. 
Published: June 2017

AbstractFacial animation is a time‐consuming and cumbersome task that requires years of experience and/or a complex and expensive set‐up. This becomes an issue, especially when animating the multitude of secondary characters required, e.g. in films or video‐games. We address this problem with a novel technique that relies on motion graphs to represent a landmarked database. Separate graphs are created for different facial regions, allowing a reduced memory footprint compared to the original data. The common poses are identified using a Euclidean‐based similarity metric and merged into the same node. This process traditionally requires a manually chosen threshold, however, we simplify it by optimizing for the desired graph compression. Motion synthesis occurs by traversing the graph using Dijkstra's algorithm, and coherent noise is introduced by swapping some path nodes with their neighbours. Expression labels, extracted from the database, provide the control mechanism for animation. We present a way of creating facial animation with reduced input that automatically controls timing and pose detail. Our technique easily fits within video‐game and crowd animation contexts, allowing the characters to be more expressive with less effort. Furthermore, it provides a starting point for content creators aiming to bring more life into their characters.
Histomorphometric and immunohistochemical assessment of RUNX2 and VEGF of Biogran™ and autogenous bone graft in human maxillary sinus bone augmentation: A prospective and randomized study
Authors: Pereira Rodrigo dos Santos , Menezes Juliana Dreyer , Bonardi João Paulo , Griza Geraldo Luiz , Okamoto Roberta , Hochuli‐Vieira Eduardo 
Published: June 2017

AbstractBackgroundFew studies have been conducted to assess new bone formation using Biogran, a bioactive glass, in maxillary sinus bone augmentation through a prospective and randomized evaluation. Moreover, there are no studies that evaluate cellular behavior by immunohistochemical assessment for osteoblastic and vascular activity during bone repair.PurposeThe aim of this study is to compare new bone formation and cellular behavior with Biogran alone, a 1:1 combination of Biogran and autogenous bone graft, and autogenous bone graft alone in human maxillary sinuses.Materials and methodsTen maxillary sinuses were grafted with Biogran (Group 1), 10 grafted with Biogran added to autogenous bone graft in a 1:1 ratio (Group 2), and 10 grafted with autogenous bone graft alone (Group 3). After 6 months of bone healing, samples were obtained concurrent to the dental implants' placement to be evaluated by histomorphometric and immunohistochemical assessment for RUNX2 and vascular endothelial growth factor (VEGF).ResultsThe amount of new bone formation in Group 1 was 42.0 ± 7.3% in the pristine bone region, 40.7 ± 14.0% in the intermediate region, and 45.6 ± 13.5% in apical region. In Group 2, for pristine bone, intermediate, and apical regions, new bone formation was 36.6 ± 12.9%, 33.2 ± 13.3%, and 45.8 ± 13.9%, respectively. Group 3 showed new bone formation of 37.3 ± 11.6%, 35.3 ± 14.7%, and 39.9 ± 15.8% in pristine bone, intermediate, and apical regions, respectively. The immunolabeling for RUNX2 showed low cellular activity in osteoblasts for all groups, and the VEGF assessment demonstrated moderate cellular activity in Groups 1 and 2; however, Group 3 presented with low activity in the pristine bone region, followed by moderate activity in the intermediate and apical region.ConclusionThis study demonstrates that Biogran and its combination with autogenous bone graft 1:1 are good bone substitutes due to their similarity to autogenous bone graft.
Dispersal to predator‐free space counterweighs fecundity costs in alate aphid morphs
Authors: RÍOS MARTÍNEZ ALDO F. , COSTAMAGNA ALEJANDRO C. 
Published: June 2017

1. Specialisation in dispersal by alate aphids often imposes constraints on other functions, particularly a reduction in fecundity due to wing development. Short‐distance flight from patches of high population density to uninfested plants may provide temporary predator‐free space, compensating for low fecundity. However, this theoretical prediction has not been explored experimentally.2. To test this hypothesis, a field cage experiment was conducted in whichAphis glycinespopulations initiated with controlled proportions of apterous and alate individuals were exposed to predation, while predator‐free space was accessible only through flight. It was predicted that an investment in alate individuals would benefit a population under predation, regardless of associated costs to fecundity.3. As expected, a strong trade‐off was observed between fecundity and wing development. However, populations initiated with a fixed proportion of alate and apterous individuals showed no reductions in final population size compared with populations initiated with apterous individuals exclusively. Moreover, the initial presence of alate individuals in the populations increased aphid prevalence (i.e. proportion of plants colonised). Similarly, both increased population size and prevalence were observed when predator‐free space was accessible through flight, as opposed to when it was inaccessible.4. These results show that despite high costs to fecundity, an investment in alate individuals is neither beneficial nor detrimental to population size when predator‐free space is accessible, but increases aphid prevalence. It is concluded that prevalence might provide an ecological advantage important enough to warrant the production of alate morphs under intense predation.
A Conceptual Framework for Evaluating Capital Equipment Purchases
Authors: Perry James H. 
Published: June 2017

Major capital equipment acquisitions present a series of unique challenges to a buyer. Factors that typically complicate the decision include technical operating differences in equipment, difficulties in defining specific operating requirements, and evaluation of the various cost factors that compose the life‐cycle cost for each equipment alternative.In this article, a conceptual model is developed to facilitate the evaluation of capital equipment alternatives in a consistent and structured fashion. The analysis involves both qualitative and quantitative data, including technical, logistical, and operating factors, as well as life‐cycle cost data. The article also presents a series of audit steps, or checkpoints, useful to a buyer in analyzing the underlying data—and it introduces an approach for dealing with the uncertainty in cost and benefit stream calculations which characterizes many major capital equipment acquisitions.
Purchasing: A Competitive Weapon
Authors: Reck Robert F. , Long Brian G. 
Published: June 2017

In a modern, well‐managed firm, the purchasing function can and should contribute to the firm's competitive goals. This article discusses how purchasing can evolve into the role of a strategic contributor through four progressive stages.Through a series of in‐depth interviews, the authors discovered that merely doing a good job of purchasing does not make the purchasing function a strategic contributor. However, those purchasing departments that have evolved to become strategic contributors to the firm's competitive goals have found the professional and financial rewards to be substantial.
Implementing Electronic Data Interchange
Authors: Monczka Robert M. , Carter Joseph R. 
Published: June 2017

Electronic data interchange (EDI) is the direct electronic transmission, computer to computer, of standard business forms between two organizations. In the purchasing environment, documents are transmitted “over the wire,” eliminating the need to generate hard copies and to distribute them manually. By utilizing EDI in purchasing, a buyer and a supplier are operating in a near ‘real‐time’ environment, which can reduce incoming material delays by shortening procurement lead times.This article is the second of two reports that present the results of a nuQor research project, funded by the Computer Information Systems and Technology Group of the National Assodation of Purchasing Management and Michigan State University, that focused on the implementation of electronic data interchange in a purchasing environment. The article presents a framework that can help managers find patterns and trends in the EDI system design and instaUation process in order to develop a useful model for EDI implementation in their firms.
Lead Time Management: Private and Public Sector Practices
Authors: Perry James H. 
Published: June 2017

Lead time management is an important element in any materials management system. The length and variance in procurement lead time directly impacts inventory investment, demand forecast accuracy, inventory turbulence, the risk of unneeded inventories, and system responsiveness. The critical significance of lead time management, however, typically is not adequately appreciated or considered in basic Department of Defense (DOD) procurement and inventory management processes. As a result, DOD inventories relative to demand have increased, and unusable inventories continue to grow.In comparison with the DOD, leading private sector firms recognize the importance of lead time management to profitability and long‐term market success. Typically they place a much a greater emphasis on time‐sensitive procurement and materials management systems; in recent years, the just‐in‐time concept has facilitated this effort. The inherent nature of these strategies mandates active lead time management.This article examines lead time management in both the DOD and private sector environments. Drawing on data collected from private sector firms, DOD vendors, and DOD inventory managers, empirical differences in lead time profiles are developed and analyzed—and specific procurement lead time differences are developed and used to illustrate the impact on inventory investment Finally, the article highlights DOD procurement and inventory management policies that negatively impact procurement lead times and recommends revisions to these policies.
The “Theory of Constraints” and the Make‐or‐Buy Decision
Authors: Gardiner Stanley C. , Blackstone John H. 
Published: June 2017

The standard cost approach and the “theory of constraints” (TOC) manufacturing philosophy are compared as bases for the make‐or‐buy decision. The authors argue that many current make‐or‐buy decisions are made improperly and that capacity‐sensitive decision procedures are needed. The standard cost method, a make‐or‐buy decision method based on the standard cost system, is illustrated and compared with the contribution per constraint minute (CPCM) and maximum permissible component price (MPCP) methods, which are based on the TOC philosophy.The CPCM method is used to compare alternatives when the prices of purchased parts are known. The MPCP method provides the buyer with an upper bound purchase price, which could be used when negotiating with a potential supplier.The standard cost method, when strictly applied, ignores the revenue component of the decision and does not consistently yield the most profitable decision. The CPCM and MPCP methods are offered as procedures that consistently choose the more profitable decision.
The highly pathogenic H5N1 influenza A virus down‐regulated several cellular MicroRNAs which target viral genome
Authors: Wang Rong , Zhang Ying‐Ying , Lu Jian‐Sheng , Xia Bing‐Hui , Yang Zhi‐Xin , Zhu Xu‐Dong , Zhou Xiao‐Wei , Huang Pei‐Tang 
Published: June 2017

AbstractHigher and prolonged viral replication is critical for the increased pathogenesis of the highly pathogenic avian influenza (HPAI) subtype of H5N1 influenza A virus (IAV) over the lowly pathogenic H1N1 IAV strain. Recent studies highlighted the considerable roles of cellular miRNAs in host defence against viral infection. In this report, using a 3′UTR reporter system, we identified several putative miRNA target sites buried in the H5N1 virus genome. We found two miRNAs, miR‐584‐5p and miR‐1249, that matched with the PB2 binding sequence. Moreover, we showed that these miRNAs dramatically down‐regulated PB2 expression, and inhibited replication of H5N1 and H1N1 IAVs in A549 cells. Intriguingly, these miRNAs expression was differently regulated in A549 cells infected with the H5N1 and H1N1 viruses. Furthermore, transfection of miR‐1249 inhibitor enhanced the PB2 expression and promoted the replication of H5N1 and H1N1 IAVs. These results suggest that H5N1 virus may have evolved a mechanism to escape host‐mediated inhibition of viral replication through down‐regulation of cellular miRNAs, which target its viral genome.
MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN
Authors: Chen Lingqiang , Li Qin , Wang Jing , Jin Song , Zheng Hongmei , Lin Jun , He Fang , Zhang Hong , Ma Sha , Mei Jian , Yu Juan 
Published: June 2017

AbstractThis study was aimed to explore the role of miR‐29b‐3p and PGRN in chondrocyte apoptosis and the initiation and progress of osteoarthritis (OA). Both miR‐29b‐3p and PGRN were up‐regulated in cartilage tissue from patients with OA. Transfection of miR‐29b‐3p mimic into rat primary chondrocytes and SW1353 chondrosarcoma cells significantly suppressed PGRN expression and release, induced apoptosis, inhibited proliferation and scratch wound closure. By contrast, transfection of miR‐29b‐3p inhibitor exhibited the opposite effects. Moreover, the expression and secretion of cartilaginous degeneration‐related molecules were also altered by miR‐29b‐3p. Luciferase reporter gene assay showed rat GRN mRNA is directly targeted and repressed by miR‐29b‐3p. The fact that recombinant PGRN or shPGRN‐mediated PGRN interference abolished miR‐29b‐3p mimic‐induced cell apoptosis and growth inhibition suggested miR‐29b‐3p affect the cellular functions of chondrocyte through regulating PGRN expression. In vivo, joint cavity injection of miR‐29b‐3p antagomir prior to surgical induction of OA significantly suppressed the upregulation of miR‐29b‐3p, whereas further promoted the increased expression of PGRN. Articular chondrocytes apoptosis and cartilage loss in the knee joint of surgically induced OA rats were also ameliorated by the injection of miR‐29b‐3p antagomir, demonstrated by TUNEL and safranin O‐fast green staining. This work showed miR‐29b‐3p facilitates chondrocyte apoptosis and OA by targeting PGRN, and miR‐29b‐3p or PGRN may be the potential target for OA treatments.
iPSC technology‐based regenerative therapy for diabetes
Authors: Kondo Yasushi , Toyoda Taro , Inagaki Nobuya , Osafune Kenji 
Published: June 2017

AbstractThe directed differentiation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of the pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β‐like cells in vitro that show glucose‐responsive insulin secretion ability. The therapeutic potentials of hESC/iPSC‐derived pancreatic cells have been evaluated using diabetic animal models, and transplantation methods including immunoprotective devices that prevent immune responses from hosts to the implanted pancreatic cells have been investigated towards the development of regenerative therapies against diabetes. These efforts led to the start of a clinical trial that involves the implantation of hESC‐derived pancreatic progenitors into type 1 diabetes patients. In addition, patient‐derived iPSCs have been generated from diabetes‐related disorders towards the creation of novel in vitro disease models and drug discovery, although few reports so far have analyzed the disease mechanisms. Considering recent advances in differentiation methods that generate pancreatic endocrine lineages, we will see the development of novel cell therapies and therapeutic drugs against diabetes based on iPSC technology‐based research in the next decade.
Psoriasis in Latin America and the Caribbean: a systematic review
Authors: Hernández‐Vásquez A. , Molinari L. , Larrea N. , Ciapponi A. 
Published: June 2017

AbstractPsoriasis is a chronic inflammatory disease that generally affects the skin, nails and joints. The burden of psoriatic disease in Latin America and the Caribbean (LAC) remains largely unknown. To estimate the burden of psoriasis in LAC. We conducted a systematic review following the MOOSE and PRISMA statements. We searched published studies in MEDLINE, EMBASE, LILACS and CENTRAL from 1st January 2000 to 5th August 2015. We included studies that reported incidence, prevalence, health resource use and health expenditures, treatment patterns, comparative effectiveness of different drugs, patients reported outcomes, adherence to treatment and patient preferences in LAC. Risk of bias was assessed evaluating selection of participants, control of cofounders, measurement of exposure and outcome and conflict of interest. Pairs of reviewers independently selected, extracted and assessed the bias risk of the studies. The systematic review was registered at PROSPERO (CRD42016038325). A total of 18 studies from 12 LAC countries were included. Most were observational studies, between which there was a large heterogeneity of outcomes. Population‐based studies were not found and most data came from hospital registries. One study reported an incidence of psoriatic arthritis in 6.26 cases per 100 000 person‐years. Another study found an incidence of psoriasis 1020 per 100 000 patient‐year attending at a dermatology clinic. The prevalence reported in the Argentinean health service was 74 cases per 100 000. Further, psoriasis has been shown to have a substantial negative impact on quality of life. A number of studies also indicated that non‐communicable disease burden increases with the presence and severity of psoriasis. With regard to treatment pattern, methotrexate was the dominant systemic therapy. In conclusion, there is an important lack of information from LAC concerning the burden of psoriasis. Further studies investigating the burden of psoriasis in representative LAC populations are needed.
Psoriasis comorbidity affects multiple sclerosis neurological progression: a retrospective case – control analysis
Authors: Miron G. , Gurevich M. , Baum S. , Achiron A. , Barzilai A. 
Published: June 2017

AbstractBackgroundMultiple sclerosis (MS) and psoriasis are inflammatory disorders, with epidemiological and biological associations. The impact of one disease on the course of the other has not been studied.ObjectiveTo characterize patients with psoriasis and MS, and to assess whether psoriasis comorbidity affected the progression of MS.MethodsA retrospective case–control study. Patients with psoriasis comorbidity were identified from 3456 patients included in the Sheba Hospital Multiple Sclerosis Center database. Clinical and demographical characteristics and MS progression‐related outcomes in patients whose follow‐up exceeded 5 years were analysed and compared to those of a matched control cohort of MS‐only (MSO) patients.ResultsForty‐five (1.3%) MS patients had psoriasis comorbidity. Psoriasis preceded MS in 35 (78%) cases. The psoriasis was defined as mild, moderate and severe in 24 (53%), twelve (27%) and nine (20%) cases respectively. MS progression‐related outcomes were evaluated in 35 patients that had follow‐up over 5 years. Patients with psoriasis onset preceding relapsing‐remitting MS (RRMS) had slower progression of disease compared to MSO patients, as manifested by a longer time to second relapse (P < 0.01) and a longer time to significant neurological disability scores (P < 0.03).ConclusionPsoriasis comorbidity preceding the onset of MS is associated with slower progression of disability.
Effect of etching on bonding of a self‐etch adhesive to dentine affected by amelogenesis imperfecta
Authors: Epasinghe Don Jeevanie , Yiu Cynthia Kar Yung 
Published: June 2017

AbstractAimDentine affected by amelogenesis imperfecta (AI) is histologically altered due to loss of hypoplastic enamel and becomes hypermineralized. In the present study, we examined the effect of additional acid etching on microtensile bond strength of a self‐etch adhesive to AI‐affected dentine.MethodsFlat coronal dentine obtained from extracted AI‐affected and non‐carious permanent molars were allocated to two groups: (a) Clearfil SE Bond (control); and (b) Clearfil SE Bond and additional etching with 34% phosphoric acid for 15 seconds. The bonded teeth were sectioned into .8‐mm2 beams for microtensile bond strength testing, and stressed to failure under tension. The bond strength data were analyzed using two‐way analysis of variance (dentine type and etching step) and Student‐Newman‐Keuls multiple comparison test (P<.05). Representative fractured beams from each group were examined under scanning electron microscopy.ResultsBoth factors, dentine substrate (P<.001) and etching step (P<.05), and their interactions (P<.001), were statistically significant. Additional etching had an adverse effect on the bond strength of Clearfil SE Bond to normal dentine (P<.005), and no significant improvement was found for AI‐affected dentine (P=.479).ConclusionAdditional acid etching does not improve the bond strength of a self‐etch adhesive to AI‐affected dentine.