bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automating the maintenance of nonfunctional system properties using demonstration‐based model transformation
Authors: Sun Yu , Gray Jeff , Delamare Romain , Baudry Benoit , White Jules 
Published: July 2013

ABSTRACTDomain‐Specific Modeling Languages (DSMLs) are playing an increasingly significant role in software development. By raising the level of abstraction using notations that are representative of a specific domain, DSMLs allow the core essence of a problem to be separated from irrelevant accidental complexities, which are typically found at the implementation level in source code. In addition to modeling the functional aspects of a system, a number of nonfunctional properties (e.g., quality of service constraints and timing requirements) also need to be integrated into models in order to reach a complete specification of a system. This is particularly true for domains that have distributed real time and embedded needs. Given a base model with functional components, maintaining the nonfunctional properties that crosscut the base model has become an essential modeling task when using DSMLs.The task of maintaining nonfunctional properties in DSMLs is traditionally supported by manual model editing or by using model transformation languages. However, these approaches are challenging to use for those unfamiliar with the specific details of a modeling transformation language and the underlying metamodel of the domain, which presents a7 steep learning curve for many users. This paper presents a demonstration‐based approach to automate the maintenance of nonfunctional properties in DSMLs. Instead of writing model transformation rules explicitly, users demonstrate how to apply the nonfunctional properties by directly editing the concrete model instances and simulating a single case of the maintenance process. By recording a user's operations, an inference engine analyzes the user's intention and generates generic model transformation patterns automatically, which can be refined by users and then reused to automate the same evolution and maintenance task in other models. Using this approach, users are able to automate the maintenance tasks without learning a complex model transformation language. In addition, because the demonstration is performed on model instances, users are isolated from the underlying abstract metamodel definitions. Our demonstration‐based approach has been applied to several scenarios, such as auto scaling and model layout. The specific contribution in this paper is the application of the demonstration‐based approach to capture crosscutting concerns representative of aspects at the modeling level. Several examples are presented across multiple modeling languages to demonstrate the benefits of our approach. Copyright © 2013 John Wiley & Sons, Ltd.
No evidence for neo-oogenesis may link to ovarian senescence in adult monkey
Authors: Yuan Jihong , Zhang Dongdong , Wang Lei , Liu Mengyuan , Mao Jian , Yin Yu , Ye Xiaoying , Liu Na , Han Jihong , Gao Yingdai , Cheng Tao , Keefe David L. , Liu Lin 
Published: July 2013

Abstract
Female germline or oogonial stem cells transiently residing in fetal ovaries are analogous to the spermatogonial stem cells or germline stem cells (GSCs) in adult testes where GSCs and meiosis continuously renew. Oocytes can be generated in vitro from embryonic stem cells and induced pluripotent stem cells, but the existence of GSCs and neo-oogenesis in adult mammalian ovaries is less clear. Preliminary findings of GSCs and neo-oogenesis in mice and humans have not been consistently reproducible. Monkeys provide the most relevant model of human ovarian biology. We searched for GSCs and neo-meiosis in ovaries of adult monkeys at various ages, and compared them with GSCs from adult monkey testis, which are characterized by cytoplasmic staining for the germ cell marker DAZL and nuclear expression of the proliferative markers PCNA and KI67, and pluripotency-associated genes LIN28 and SOX2, and lack of nuclear LAMIN A, a marker for cell differentiation. Early meiocytes undergo homologous pairing at prophase I distinguished by synaptonemal complex lateral filaments with telomere perinuclear distribution. By exhaustive searching using comprehensive experimental approaches, we show that proliferative GSCs and neo-meiocytes by these specific criteria were undetectable in adult mouse and monkey ovaries. However, we found proliferative nongermline somatic stem cells that do not express LAMIN A and germ cell markers in the adult ovaries, notably in the cortex and granulosa cells of growing follicles. These data support the paradigm that adult ovaries do not undergo germ cell renewal, which may contribute significantly to ovarian senescence that occurs with age.
Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice
Authors: Coulson-Thomas Vivien Jane , Caterson Bruce , Kao Winston W.-Y. 
Published: July 2013

AbstractMucopolysaccharidosis (MPS) are a family of related disorders caused by a mutation in one of the lysosomal exoglycosidases which leads to the accumulation of glycosaminoglycans (GAGs). MPS VII, caused by a mutation in β-glucuronidase, manifests hepatomegaly, skeletal dysplasia, short stature, corneal clouding, and developmental delay. Current treatment regimens for MPS are not effective for treating corneal clouding and impaired mental development. We hypothesized that human umbilical mesenchymal stem cells (UMSCs) transplanted into the corneal stroma could participate in the catabolism of GAGs providing a means of cell therapy for MPS. For such treatment, human UMSCs were intrastromally transplanted into corneas of MPS VII mice. UMSC transplantation restored the dendritic and hexagonal morphology of host keratocytes and endothelial cells, respectively, and in vivo confocal microscopy (HRT-II) revealed reduced corneal haze. Immunohistochemistry using antibodies against heparan sulfate and chondroitin sulfate chains as well as lysosomal-associated membrane protein 2 revealed a decrease in GAG content and both lysosomal number and size in the treated corneas. Labeling UMSC intracellular compartments prior to transplantation revealed the distribution of UMSC vesicles throughout the corneal stroma and endothelium. An in vitro coculture assay between skin fibroblasts isolated from MPS VII mice and UMSC demonstrated that neutral vesicles released by the UMSC are taken up by the fibroblasts and proceed to fuse with the acidic lysosomes. Therefore, transplanted UMSCs participate both in extracellular GAG turnover and enable host keratocytes to catabolize accumulated GAG products, suggesting that UMSC could be a novel alternative for treating corneal defects associated with MPS and other congenital metabolic disorders.
Lgr4 is a key regulator of prostate development and prostate stem cell differentiation
Authors: Luo Weijia , Rodriguez Melissa , Valdez Joseph M. , Zhu Xinglei , Tan Kunrong , Li Dali , Siwko Stefan , Xin Li , Liu Mingyao 
Published: July 2013

Abstract
echanisms modulating prostate cell fate determination remain unexplored. The leucine-rich repeat containing G-protein-coupled receptors (Lgr) have been identified as important stem cell markers in various tissues. Here, we investigated the roles of Lgr4/Gpr48 in prostate stem cells (PSCs) and development. Lgr4 was ubiquitously expressed during early prostate development prior to lineage specification, with adult expression restricted to a few basal cells (principally Lin−Sca1+CD49f+). Lgr4−/− mice had compromised branching morphogenesis and delayed epithelial differentiation, leading to decreased prostate size and impaired luminal cell function. In vitro prostate sphere culture revealed that Lgr4−/− Lin−/Sca1+/CD49f+ cells failed to generate p63low cells, indicating a differentiation deficiency. Furthermore, Lgr4 ablation arrested PSC differentiation of in vivo kidney capsule prostate grafts, suggesting that Lgr4 modulates PSC properties independent of hormonal and mesenchymal effects. Analysis of neonatal prostates and prostate spheres revealed a decrease in Wnt, Sonic Hedgehog, and Notch1 expression in Lgr4−/− cells. Lgr4 loss blocked differentiation of prostate sphere p63hi cells to p63low. Treatment with exogenous Sonic Hedgehog partially restored the differentiation of p63hi cells in Lgr4−/− spheres. Taken together, our data revealed the roles of Lgr4 in early prostate development and in stem cell differentiation through regulation of the Wnt, Notch, and Sonic Hedgehog signaling pathways.
Developmental and oncogenic radiation effects on neural stem cells and their differentiating progeny in mouse cerebellum
Authors: Tanori Mirella , Pasquali Emanuela , Leonardi Simona , Casciati Arianna , Giardullo Paola , Stefano Ilaria , Mancuso Mariateresa , Saran Anna , Pazzaglia Simonetta 
Published: July 2013

Abstract
Neural stem cells are highly susceptible to radiogenic DNA damage, however, little is known about their mechanisms of DNA damage response (DDR) and the long-term consequences of genotoxic exposure. Patched1 heterozygous mice (Ptc1+/−) provide a powerful model of medulloblastoma (MB), a frequent pediatric tumor of the cerebellum. Irradiation of newborn Ptc1+/− mice dramatically increases the frequency and shortens the latency of MB. In this model, we investigated the mechanisms through which multipotent neural progenitors (NSCs) and fate-restricted progenitor cells (PCs) of the cerebellum respond to DNA damage induced by radiation, and the long-term developmental and oncogenic consequences. These responses were assessed in mice exposed to low (0.25 Gy) or high (3 Gy) radiation doses at embryonic day 13.5 (E13.5), when NSCs giving rise to the cerebellum are specified but the external granule layer (EGL) has not yet formed, or at E16.5, during the expansion of granule PCs to form the EGL. We found crucial differences in DDR and apoptosis between NSCs and fate-restricted PCs, including lack of p21 expression in NSCs. NSCs also appear to be resistant to oncogenesis from low-dose radiation exposure but more vulnerable at higher doses. In addition, the pathway to DNA repair and the pattern of oncogenic alterations were strongly dependent on age at exposure, highlighting a differentiation-stage specificity of DNA repair pathways in NSCs and PCs. These findings shed light on the mechanisms used by NSCs and PCs to maintain genome integrity during neurogenesis and may have important implications for radiation risk assessment and for development of targeted therapies against brain tumors.
MEK/ERK signaling directly and indirectly contributes to the cyclical self-renewal of spermatogonial stem cells
Authors: Hasegawa Kazuteru , Namekawa Satoshi H. , Saga Yumiko 
Published: July 2013

Abstract
Coordination of stem cell fate is regulated by extrinsic niche signals and stem cell intrinsic factors. In mammalian testes, spermatogonial stem cells maintain constant production of abundant spermatozoa by alternating between self-renewal and differentiation at regular intervals according to a periodical program known as the seminiferous epithelial cycle. Although retinoic acid (RA) signaling has been suggested to direct the cyclical differentiation of spermatogonial stem cells, it remains largely unclear how their cycle-dependent self-renewal/proliferation is regulated. Here, we show that MEK/ERK signaling contributes to the cyclical activity of spermatogonial stem cells. We found that ERK1/2 is periodically activated in Sertoli cells during the stem cell self-renewal/proliferation phase, and that MEK/ERK signaling is required for the stage-related expression of the critical niche factor GDNF. In addition, ERK1/2 is activated in GFRα1-positive spermatogonial stem cells under the control of GDNF and prevent them from being differentiated. These results suggest that MEK/ERK signaling directly and indirectly maintains spermatogonial stem cells by mediating a signal that promotes their periodical self-renewal/proliferation. Conversely, RA signaling directly and indirectly induces differentiation of spermatogonial stem cells. We propose that temporally regulated activations of RA signaling and a signal regulating MEK/ERK antagonistically coordinates the cycle-related activity of spermatogonial stem cells.
Additional value of prenatal genomic array testing in fetuses with isolated structural ultrasound abnormalities and a normal karyotype: a systematic review of the literature
Authors: de wit M. C. , Srebniak M. I. , Govaerts L. C. P. , Van Opstal D. , Galjaard R. J. H. , Go A. T. J. I. 
Published: July 2013

ABSTRACTOBJECTIVETo establish the prevalence of submicroscopic genetic copy number variants (CNVs) in fetuses with a structural ultrasound anomaly (restricted to one anatomical system) and a normal karyotype. The aim was to determine the diagnostic and prognostic value of genomic array testing in these pregnancies.MethodsEmbase and PubMed databases were systematically searched for all relevant articles on prevalence of pathogenic submicroscopic CNVs in fetuses with ultrasound anomalies. Reported cases were sorted into groups according to anatomical site of the detected ultrasound anomaly. The prevalence of causative submicroscopic CNVs was calculated for each group.ResultsCombined data of the reviewed studies (n = 18) indicated that fetuses with an ultrasound anomaly restricted to one anatomical system (n = 2220) had a 3.1–7.9% chance of carrying a causative submicroscopic CNV, depending on the anatomical system affected. This chance increased to 9.1% for fetuses with multiple ultrasound anomalies (n = 1139).ConclusionThis review indicates that 3.1–7.9% of fetuses with a structural ultrasound anomaly restricted to one anatomical system and a normal karyotype will show a submicroscopic CNV, which explains its phenotype and provides information for fetal prognosis. Therefore, we conclude that microarray has considerable diagnostic and prognostic value in these pregnancies. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
Stress intensity factor for an infinite plane containing three collinear cracks under compression
Authors: Zheng T. , Zhu Z. , Wang B. , Zeng L. 
Published: July 2013

AbstractThe fracture behaviour of multi‐cracked materials has become a key issue in fracture mechanics and has received large attention recently. In this paper, an infinite plane containing three collinear cracks under biaxial compression has been investigated. Considering crack surface friction and using complex stress function theory, the exact analytical solution of stress intensity factors (SIFs) for an infinite plane containing three collinear cracks is obtained. The corresponding finite element code of Abaqus is employed to validate the theoretical results, and its results agree very well with the theoretical results. The effects of confining stresses, crack distances and the crack surface frictions on SIFs are analyzed through the theoretical results and the Abaqus code. A photoelastic experiment was conducted to validate the theoretical result about the effect of confining stresses.
Strong solutions to the Navier–Stokes–Fourier system with slip–inflow boundary conditions
Authors: Piasecki T. , Pokorný M. 
Published: July 2013

AbstractWe consider a system of partial differential equations describing the steady flow of a compressible heat conducting Newtonian fluid in a three‐dimensional channel with inflow and outflow part. We show the existence of a strong solution provided the data are close to a constant, but nontrivial flow with sufficiently large dissipation in the energy equation.
The demography of native and non‐native plant species in mountain systems: examples in the Greater Yellowstone Ecosystem
Authors: Pollnac Fredric W. , Maxwell Bruce D. , Taper Mark L. , Rew Lisa J. 
Published: July 2013

AbstractIn mountainous areas, native and non‐native plants will be exposed to climate change and increased disturbance in the future. Non‐native plants may be more successful than natives in disturbed areas and thus be able to respond quicker to shifting climatic zones. In 2009, monitoring plots were established for populations of a non‐native species (Linaria dalmatica) and a closely related native species (Castilleja miniata) on an elevation gradient in the Greater Yellowstone Ecosystem, USA. Population data were collected twice during the growing season for 3 years and used to calculate population vital rates for both species, and to construct population dynamics models forL. dalmatica.Linaria dalmaticavital rates were more associated with climatic/environmental factors than those ofC. miniata. Population dynamics models forL. dalmaticashowed no trend in population growth rate (λ) vs. elevation. The highestλcorresponded with the lowest vegetation and litter cover, and the highest bare ground cover. All populations withλ< 1 corresponded with the lowest measured winter minimum temperature. There was a negative association betweenλand number of weeks of adequate soil moisture, and a weak positive association betweenλand mean winter minimum temperature. Variance in vital rates andλofL. dalmaticasuggest broad adaptation within its current range, with the potential to spread further with or without future changes in climate. There is evidence thatλis negatively affected by persistent soil moisture which promotes the growth of other plant species, suggesting that it might expand further if other species were removed by disturbance.
Comparison of non-linear models to describe the lactation curves of milk yield and composition in Iranian Holsteins
Authors: HOSSEIN-ZADEH N. GHAVI 
Published: July 2013

SUMMARYIn order to describe the lactation curves of milk yield (MY) and composition, six non-linear mathematical equations (Wood, Dhanoa, Sikka, Nelder, Hayashi and Dijkstra) were used. Data were 5 535 995 test-day records for MY, fat (FC) and protein (PC) contents and somatic cell score (SCS) from the first three lactations of Iranian Holstein cows that were collected on 2547 dairy herds in the period from 2000 to 2011 by the Animal Breeding Center of Iran. Each model was fitted to monthly production records of dairy cows using the NLIN and MODEL procedures in SAS and the parameters were estimated. The models were tested for goodness of fit using root-mean-square error (RMSE), Durbin–Watson statistic (DW) and Akaike's information criterion (AIC). The Wood and Dhanoa models provided the best fit of the lactation curve for MY in the first and second parities due to the lower values of RMSE and AIC than other models; but the Dijkstra model showed the best fit of milk lactation curve for third-parity dairy cows, FC, PC and SCS in the first three parities because of the lowest values of RMSE and AIC. Also, In general, the Sikka model did not fit the production data as well as the other equations. The results showed that the Dijkstra equation was able to estimate the time to the peak and peak MY more accurately than the other equations. However, the Wood equation provided more accurate predictions of peak MY at second- and third parities than the other equations. For first lactation FC, the Dijkstra equation was able to estimate the minimum FC and for second- and third-parity FC, the Wood equation provided more accurate predictions of minimum FC. For first- and second-lactation PC, the Dijkstra equation was able to estimate the minimum PC but for third parity, the minimum value of PC was predicted more accurately by the Wood model. The Dhanoa and Dijkstra equations for first lactation SCS and the Dhanoa equation for second- and third- lactation SCS were able to estimate the minimum SCS more accurately than the other equations. Overall, evaluation of different equations used in the current study indicated the potential of the non-linear functions for fitting monthly productive records of Holstein cows.
Abundance and density estimates for common leopard Panthera pardus and clouded leopard Neofelis nebulosa in Manas National Park, Assam, India
Authors: Borah Jimmy , Sharma Tridip , Das Dhritiman , Rabha Nilmani , Kakati Niraj , Basumatary Ajit , Ahmed M. Firoz , Vattakaven Joseph 
Published: July 2013

AbstractEffective conservation of rare carnivores requires reliable estimates of population density for prioritizing investments and assessing the effectiveness of conservation interventions. We used camera traps and capture–recapture analysis to provide the first reliable abundance and density estimates for the common leopard Panthera pardus and clouded leopard Neofelis nebulosa in Manas National Park, India. In 57 days of camera trapping, with a total of 4,275 camera-trap days, we photo-captured 27 individually identified common leopards (11 males, 13 females and three unidentified), and 16 clouded leopards (four males, five females and seven unidentified). The abundance estimates using the Mh jackknife and Pledger model Mh were 47.0 and 35.6, respectively, for the common leopard, and 21.0 and 25.0, respectively, for the clouded leopard. Density estimates using maximum likelihood spatially-explicit capture–recapture were 3.4 ± SE 0.82 and 4.73 ± SE 1.43 per 100 km2 for the common and clouded leopards, respectively. Spatially-explicit capture–recapture provided more realistic density estimates compared with those obtained from conventional methods. Our data indicates that camera trapping using a capture–recapture framework is an effective tool for assessing population sizes of cryptic and elusive carnivores such as the common and clouded leopards. The study has established a baseline for the long-term monitoring programme for large carnivores in Manas National Park.
Protonation and pK changes in protein–ligand binding
Authors: Onufriev Alexey V. , Alexov Emil 
Published: July 2013

AbstractFormation of protein–ligand complexes causes various changes in both the receptor and the ligand. This review focuses on changes in pK and protonation states of ionizable groups that accompany protein–ligand binding. Physical origins of these effects are outlined, followed by a brief overview of the computational methods to predict them and the associated corrections to receptor–ligand binding affinities. Statistical prevalence, magnitude and spatial distribution of the pK and protonation state changes in protein–ligand binding are discussed in detail, based on both experimental and theoretical studies. While there is no doubt that these changes occur, they do not occur all the time; the estimated prevalence varies, both between individual complexes and by method. The changes occur not only in the immediate vicinity of the interface but also sometimes far away. When receptor–ligand binding is associated with protonation state change at particular pH, the binding becomes pH dependent: we review the interplay between sub-cellular characteristic pH and optimum pH of receptor–ligand binding. It is pointed out that there is a tendency for protonation state changes upon binding to be minimal at physiologically relevant pH for each complex (no net proton uptake/release), suggesting that native receptor–ligand interactions have evolved to reduce the energy cost associated with ionization changes. As a result, previously reported statistical prevalence of these changes – typically computed at the same pH for all complexes – may be higher than what may be expected at optimum pH specific to each complex. We also discuss whether proper account of protonation state changes appears to improve practical docking and scoring outcomes relevant to structure-based drug design. An overview of some of the existing challenges in the field is provided in conclusion.