bluuebunny/crossref_metadata_2025 huggingface dataset:
The Basis for Evolution of DNA-Binding Specificity of the Aft1 Transcription Factor in Yeasts
Authors: Gonçalves Isabelle R , Conde e Silva Natalia , Garay Cesar La Torre , Lesuisse Emmanuel , Camadro Jean Michel , Blaiseau Pierre Louis
Published: October 2013

The Saccharomyces cerevisiae  Aft1 and Kluyveromyces lactis KlAft are orthologous yeast transcription activators that regulate the expression of the same group of iron-uptake genes but bind to the different DNA sites: TGCACCC for Aft1 and PuCACCC for KlAft. To establish whether the DNA-binding mechanisms of Aft1 and KlAft have diverged during the evolution of the Aft-type transcription factor, we examined the function of a nonconserved region in their DNA-binding domains. A large part of this region is composed of a sequence predicted to be disordered in structure and potentially phosphorylated. We show with deletion mutant analyses that this sequence is essential for the binding of Aft1 to its DNA site and for the iron uptake and growth of S. cerevisiae under iron-limited conditions. We constructed hybrid proteins by exchanging the nonconserved regions of Aft1 and KlAft. We show that the Aft1 region is necessary and sufficient for KlAft to bind efficiently to the Aft1 DNA site in S. cerevisiae and to complement the iron-dependent phenotype of the aft1Δaft2Δ mutant. This demonstrates that the changes in the nonconserved region of the Aft-type DNA-binding domain have led to changes in the DNA-binding specificity and have major consequences for the regulation of iron homeostasis. The combination of bioinformatic and experimental analyses indicates that the sequence TGCACCC is the most probable ancestral Aft-type element. Our findings suggest that the changes in the nonconserved region of the DNA-binding domain are responsible for the evolution of the TGCACCC sequence toward PuCACCC in the K. lactis species.
A Novel Role for Cet1p mRNA 5′-Triphosphatase in Promoter Proximal Accumulation of RNA Polymerase II in Saccharomyces cerevisiase
Authors: Lahudkar Shweta , Durairaj Geetha , Uprety Bhawana , Bhaumik Sukesh R
Published: October 2013

Yeast mRNA 5′-triphosphatase, Cet1p, recognizes phosphorylated-RNA polymerase II as a component of capping machinery via Ceg1p for cotranscriptional formation of mRNA cap structure that recruits cap-binding complex (CBC) and protects mRNA from exonucleases. Here, we show that the accumulation of RNA polymerase II at the promoter proximal site of ADH1 is significantly enhanced in the absence of Cet1p. Similar results are also found at other genes. Cet1p is recruited to the 5′ end of the coding sequence, and its absence impairs mRNA capping, and hence CBC recruitment. However, such an impaired recruitment of CBC does not enhance promoter proximal accumulation of RNA polymerase II. Thus, Cet1p specifically lowers the accumulation of RNA polymerase II at the promoter proximal site independently of mRNA cap structure or CBC. Further, we show that Cet1p’s N-terminal domain, which is not involved in mRNA capping, decreases promoter proximal accumulation of RNA polymerase II. An accumulation of RNA polymerase II at the promoter proximal site in the absence of Cet1p’s N-terminal domain is correlated with reduced transcription. Collectively, our results demonstrate a novel role of Cet1p in regulation of promoter proximal accumulation of RNA polymerase II independently of mRNA capping activity, and hence transcription in vivo.
Current Approaches of Bone Morphogenetic Proteins in Dentistry
Authors: Díaz-Sánchez Rosa-María , Yáñez-Vico Rosa-María , Fernández-Olavarría Ana , Mosquera-Pérez Regina , Iglesias-Linares Alejandro , Torres-Lagares Daniel
Published: October 2013

Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration.
Qualidade do bacalhau salgado seco comercializado em temperatura ambiente e refrigerado
Authors: Baltazar Camila , Sanches Sandra Abelardo , Telles Evelise Oliveira , Merusse José Luiz Bernardino , Balian Simone de Carvalho
Published: October 2013

O comércio varejista brasileiro expõe o bacalhau salgado seco, inteiro ou em porções, sem refrigeração. Esta condição, tradicionalmente aceita pelos consumidores, contraria as especificações do fabricante de manter o produto sob refrigeração, o que frequentemente gera conflitos entre as autoridades sanitárias e o comércio. Perante este fato, o presente estudo avaliou parâmetros microbiológicos e físico-químicos de 56 amostras de bacalhau obtidas no município de São Paulo-SP, armazenadas sob refrigeração (0 ° C a 5 ° C) e em temperatura ambiente (20 ° C a 25 ° C), com zero, sete e 14 dias de armazenamento. As amostras foram agrupadas em quatro categorias: (A) amostras refrigeradas não manipuladas e (B), (C) e (D) manipuladas, respectivamente, com zero, sete e 14 dias de armazenamento em temperatura ambiente. A temperatura ambiente variou de 20,5 ° C a 23,5 ° C e a umidade relativa do ar, de 52,5 a 67 %. Foram pesquisados: Staphylococcus coagulase positiva, Clostridium sulfito redutores, coliformes totais e termotolerantes, Salmonella spp., bolores, leveduras e bactérias halofílicas. As análises físico-químicas realizadas foram: umidade, pH, atividade de água (Aa) e resíduo mineral fixo. Não houve diferenças nos resultados microbiológicos obtidos entre as quatro categorias e estes se apresentaram dentro dos limites estabelecidos pela legislação brasileira. Com relação às análises físico-químicas, também não houve diferença estatística entre as quatro categorias. Os valores médios obtidos, por categoria, foram: A: 54,9 % de umidade; Aa = 0,748; pH = 6,0; B: 54,0 % de umidade; Aa = 0,749; pH = 6,0; C: 49,1 % de umidade; Aa = 0,749; pH = 6,0, e para a categoria D: 50,7 % de umidade; Aa = 0,748; pH = 6,0 e 21,6 % de resíduo mineral fixo. Todos os valores de umidade encontrados estavam acima do padrão (35 %); os valores de pH obtidos estavam de acordo com o padrão (6 a 7) e os valores de resíduo mineral fixo atenderam à legislação vigente (mín. 12 %). Com relação à Aa, os valores sugerem que esta é uma importante barreira para o desenvolvimento microbiano e, embora não haja padrão para este parâmetro, julga-se necessário determinar um valor referência como limite máximo. Conclui-se que, nas condições do presente estudo, o comércio do bacalhau salgado seco mantido sob refrigeração ou em temperatura ambiente por 14 dias oferece as mesmas condições de segurança sanitária para o consumidor.
Demography of a reintroduced population: moving toward management models for an endangered species, the Whooping Crane
Authors: Servanty Sabrina , Converse Sarah J. , Bailey Larissa L.
Published: October 2013

The reintroduction of threatened and endangered species is now a common method for reestablishing populations. Typically, a fundamental objective of reintroduction is to establish a self‐sustaining population. Estimation of demographic parameters in reintroduced populations is critical, as these estimates serve multiple purposes. First, they support evaluation of progress toward the fundamental objective via construction of population viability analyses (PVAs) to predict metrics such as probability of persistence. Second, PVAs can be expanded to support evaluation of management actions, via management modeling. Third, the estimates themselves can support evaluation of the demographic performance of the reintroduced population (e.g., via comparison with wild populations). For each of these purposes, thorough treatment of uncertainties in the estimates is critical. Recently developed statistical methods (namely, hierarchical Bayesian implementations of state‐space models) allow for effective integration of different types of uncertainty in estimation. We undertook a demographic estimation effort for a reintroduced population of endangered Whooping Cranes with the purpose of ultimately developing a Bayesian PVA for determining progress toward establishing a self‐sustaining population, and for evaluating potential management actions via a Bayesian PVA‐based management model. We evaluated individual and temporal variation in demographic parameters based upon a multi‐state, mark‐recapture model. We found that survival was relatively high across time and varied little by sex. There was some indication that survival varied by release method. Survival was similar to that observed in the wild population. Although overall reproduction in this reintroduced population is poor, birds formed social pairs when relatively young, and once a bird was in a social pair, it had a nearly 50% chance of nesting the following breeding season. Also, once a bird had nested, it had a high probability of nesting again. These results are encouraging, considering that survival and reproduction have been major challenges in past reintroductions of this species. The demographic estimates developed will support construction of a management model designed to facilitate exploration of management actions of interest, and will provide critical guidance in future planning for this reintroduction. An approach similar to what we describe could be usefully applied to many reintroduced populations.
Risk of posttransplant lymphoproliferative disorder associated with use of belatacept
Authors: Martin Spencer T. , Powell Jaclyn T. , Patel Monank , Tsapepas Demetra
Published: October 2013

Purpose

Published evidence on a rare but serious malignancy associated with use of the first biological agent approved for long-term maintenance immunosuppression in renal transplant recipients is reviewed.

Belatacept (Nulojix, Bristol-Myers Squibb) is approved by the Food and Drug Administration for use in combination therapy to prevent renal graft rejection in patients who are Epstein-Barr virus seropositive. Belatacept appears to offer some advantages over calcineurin inhibitor-based regimens (e.g., no need for therapeutic drug monitoring), but its use poses a risk of posttransplant lymphoproliferative disorder (PTLD), a rapidly progressing and often lethal malignancy. The efficacy and safety of more-intensive and less-intensive belatacept regimens were established in two Phase III clinical trials, which found that rates of patient and graft survival were comparable to those in cyclosporine users; belatacept was shown to be superior in preserving renal function. The occurrence of PTLD, particularly PTLD involving the central nervous system, in 0–4% of belatacept-treated patients in clinical trials prompted postmarketing initiatives: (1) implementation of a risk evaluation and mitigation strategy (REMS) program to help ensure the safe and proper use of belatacept, (2) longitudinal studies to better define the risks and outcomes of belatacept therapy, and (3) a manufacturer-created patient registry to track belatacept use and encourage voluntary reporting of associated adverse events.

Conclusion

Appropriate patient selection and adherence to REMS requirements, including patient counseling and facilitation of registry enrollment, are essential in mitigating the increased risk of PTLD associated with belatacept therapy.
Effect of Wildfires on Physicochemical Changes of Watershed Dissolved Organic Matter
Authors: Revchuk Alex D. , Suffet I. H. (Mel)
Published: October 2013

Physicochemical characterization of dissolved organic carbon (DOC) provides essential data to describe watershed characteristics after drastic changes caused by wildfires. Post‐fire watershed behavior is important for water source selection, management, and drinking water treatment optimization. Using ash and other burned vegetation fragments, a leaching procedure was implemented to describe physicochemical changes to watershed DOC caused by wildfires. Samples were collected after the 2007 and 2009 wildfires near Santa Barbara, California. Substantial differences in size distribution (measured by ultrafiltration), polarity (measured by polarity rapid assessment method), and the origin of leached DOC (measured by fluorescence) were observed between burned and unburned sites. Recently burned ash had 10 times the DOC leaching potential, and was dominated by large size fragments, compared to weathered 2‐year‐old ash. Charged DOC fractions were found to positively correlate with DOC size, whereas hydrophobic and hydrophilic DOC fractions were not. Proteins were only observed in recently burned ash and were indicative of recent post‐fire biological activity.
Removal of Copper Ions From Water Using Epichlorohydrin Cross‐Linked β‐Cyclodextrin Polymer: Characterization, Isotherms and Kinetics
Authors: Sikder M. Tajuddin , Islam Md Shariful , Kikuchi Tohru , Suzuki Junichi , Saito Takeshi , Kurasaki Masaaki
Published: October 2013

β‐cyclodextrin (β‐CD) cross‐linked with epichlorohydrin to form water insoluble β‐cyclodextrin polymer (β‐CDP) has been shown to be an effective sorbent for sorption of organic particles, but the sorption of copper (Cu2+) in aqueous solutions by β‐CDP has not been conducted. The objective of this study was to explore the sorption mechanism of β‐CDP for copper. The effects of different experimental conditions such as pH, ionic strength, contact time, and temperature were inspected using a batch method. In addition, binding scheme was estimated by using Fourier transform infrared (FTIR) spectroscopy, X‐ray photoelectron spectroscopy (XPS), a scanning electron microscope (SEM), and Brunauer‐Emmett‐Teller (BET) analysis. The adsorption of Cu2+ was observed to be higher at pH 6.0. The kinetic study revealed that the adsorption is fitted well by the pseudo‐second‐order kinetic model. The maximum binding of Cu2+ was estimated to be 111.11 mg/g through the Langmuir isotherm model — much higher than the existing sorption technologies. Hence, the adsorption‐desorption trends of epichlorohydrin cross‐linked with β‐CD, along with its good recyclability, establish an alternative, effective, and novel remediation technology for the removal of Cu2+ from aqueous solutions.
Fuzzy filters of BE-algebras
Authors: Dymek Grzegorz , Walendziak Andrzej
Published: October 2013

Characterizations of fuzzy filters in a BE-algebra are established. Conditions for a fuzzy set to be a fuzzy filter are given. For a fuzzy set µ the least fuzzy filter containing µ is constructed. The homomorphic properties of fuzzy filters of a BE-algebra are provided. Finally, characterizations of Noetherian BE-algebras and Artinian BE-algebras via fuzzy filters are obtained.
Clean unital ℓ-groups
Authors: Hager Anthony , Kimber Chawne , McGovern Warren
Published: October 2013

A ring with identity is said to be clean if every element can be written as a sum of a unit and an idempotent. The study of clean rings has been at the forefront of ring theory over the past decade. The theory of partially-ordered groups has a nice and long history and since there are several ways of relating a ring to a (unital) partially-ordered group it became apparent that there ought to be a notion of a clean partially-ordered group. In this article we define a clean unital lattice-ordered group; we state and prove a theorem which characterizes clean unital ℓ-groups. We mention the relationship of clean unital ℓ-groups to algebraic K-theory. In the last section of the article we generalize the notion of clean to the non-unital context and investigate this concept within the framework of W-objects, that is, archimedean ℓ-groups with distinguished weak order unit.
The arc length variational formula on the exponential manifold
Authors: Zhang Fengyun , Sun Huafei , Jiu Lin , Peng Linyu
Published: October 2013

In this paper, we mainly consider the first and second arc length variational problems on the exponential statistical manifold, and give the variational formulae.
Celebrating International Year of Forests 2011
Authors: Editor The
Published: October 2013

DOI: http://dx.doi.org/10.3126/banko.v21i1.9057 Banko Janakari, Vol. 21, No. 1 2011; 1-2
Status of blue sheep and Himalayan tahr in Dhorpatan Hunting Reserve, Nepal
Authors: Karki JB , Thapa BB
Published: October 2013

A survey of blue sheep (Pseudois nayaur) was conducted in six blocks of Dhorpatan Hunting Reserve (DHR), Nepal. A total of 852 blue sheep were recorded in 73 different groups. The average group size was found to be 11.7 individuals. The average population density of blue sheep in the reserve was found to be 1.28 animals per km2. There were 263 rams, 307 ewes, 89 yearlings and 39 lambs. Among the rams, 126 were classified as trophy rams, 92 as medium rams and 45 as young rams. The ratio of trophy rams to other rams was found to be higher than those found in the earlier studies. The mean sex ratio was 86 males per 100 females and the yearling to ewes ratio was 29 per 100 ewes. The survey of Himalayan tahr (Hemitragus jemlahicus) in Sundaha block recorded 53 individuals with 30 males, 14 females, eight yearlings, and one lamb. The results indicated that the existing quota of blue sheep hunting can be safely continued. In case of higher demands, two more quotas can be added to Barse, Dogadi and Sundaha blocks for the next five years (2008-2012). Himalayan tahrs can be hunted in all the blocks. Sundaha block can sustain four while the rest of the blocks can sustain two Himalayan tahrs per year. DOI: http://dx.doi.org/10.3126/banko.v21i1.9060 Banko Janakari, Vol. 21, No. 1 2011; 25-30
Assessment of climate change and its impact on cashcrops in Lwang Ghalel of Kaski district
Authors: Khadka CB , Balla MK , Tiwari KR
Published: October 2013

This paper focuses on climate change, its impact on cash crop production, perception of local people and their adaptation measures against the impacts of climate change in Lwang Ghalel Village Development Commitee (VDC) of Kaski district. Cash-crops such as tea, Amriso (broom grass) and cardamom were the main products in the study area. Primary data were collected through household survey with semi-structured questionnaires, interview with key informants, and formal and informal discussion. Thirty years meteorological data (rainfall and temperature) were collected from Narayani Basin Office, Pokhara to study the rainfall and temperature pattern. The rainfall pattern seemed to be increased at the rate of 2.74 mm per year while the mean annual maximum and minimum temperature also seemed to be increased by 0.064°C and 0.01°C per year, respectively. Tea was affected more due to climate change than other cash-crops. Amriso was the best adapted species against climate change due to its extended root system. DOI: http://dx.doi.org/10.3126/banko.v21i1.9061 Banko Janakari, Vol. 21, No. 1 2011; 31-34
A comparison of supraglacial lake observations derived from MODIS imagery at the western margin of the Greenland ice sheet
Authors: Leeson Amber A. , Shepherd Andrew , Sundal Aud V. , Malin Johansson A. , Selmes Nick , Briggs Kate , Hogg Anna E. , Fettweis Xavier
Published: October 2013

Supraglacial lakes (SGLs) affect the dynamics of the Greenland ice sheet by storing runoff and draining episodically. We investigate the evolution of SGLs as reported in three datasets, each based on automated classification of satellite imagery. Although the datasets span the period 2001–10, there are differences in temporal sampling, and only the years 2005–07 are common. By subsampling the most populous dataset, we recommend a sampling frequency of one image per 6.5 days in order to minimize uncertainty associated with poor temporal sampling. When compared with manual classification of satellite imagery, all three datasets are found to omit a sizeable (29, 48 and 41 %) fraction of lakes and are estimated to document the average size of SGLs to within 0.78, 0.48 and 0.95 km2. We combine the datasets using a hierarchical scheme, producing a single, optimized, dataset. This combined record reports up to 67% more lakes than a single dataset. During 2005–07, the rate of SGL growth tends to follow the rate at which runoff increases in each year. In 2007, lakes drain earlier than in 2005 and 2006 and remain absent despite continued runoff. This suggests that lakes continue to act as open surface–bed conduits following drainage.
Formic Acid Oxidation over Hierarchical Porous Carbon Containing PtPd Catalysts
Authors: Baena-Moncada Angélica , Morales Gustavo , Barbero Cesar , Planes Gabriel , Florez-Montaño Jonathan , Pastor Elena
Published: October 2013

The use of high surface monolithic carbon as support for catalysts offers important advantage, such as elimination of the ohmic drop originated in the interparticle contact and improved mass transport by ad-hoc pore design. Moreover, the approach discussed here has the advantage that it allows the synthesis of materials having a multimodal porous size distribution, with each pore size contributing to the desired properties. On the other hand, the monolithic nature of the porous support also imposes new challenges for metal loading. In this work, the use of Hierarchical Porous Carbon (HPC) as support for PtPd nanoparticles was explored. Three hierarchical porous carbon samples (denoted as HPC-300, HPC-400 and HPC-500) with main pore size around 300, 400 and 500 nm respectively, are used as porous support. PtPd nanoparticles were loaded by impregnation and subsequent chemical reduction with NaBH4. The resulting material was characterized by EDX, XRD and conventional electrochemical techniques. The catalytic activity toward formic acid and methanol electrooxidation was evaluated by electrochemical methods, and the results compared with commercial carbon supported PtPd. The Hierarchical Porous Carbon support discussed here seems to be promising for use in DFAFC anodes.
Applying Evidence-Based Medicine in Telehealth: An Interactive Pattern Recognition Approximation
Authors: Fernández-Llatas Carlos , Meneu Teresa , Traver Vicente , Benedi José-Miguel
Published: October 2013

Born in the early nineteen nineties, evidence-based medicine (EBM) is a paradigm intended to promote the integration of biomedical evidence into the physicians daily practice. This paradigm requires the continuous study of diseases to provide the best scientific knowledge for supporting physicians in their diagnosis and treatments in a close way. Within this paradigm, usually, health experts create and publish clinical guidelines, which provide holistic guidance for the care for a certain disease. The creation of these clinical guidelines requires hard iterative processes in which each iteration supposes scientific progress in the knowledge of the disease. To perform this guidance through telehealth, the use of formal clinical guidelines will allow the building of care processes that can be interpreted and executed directly by computers. In addition, the formalization of clinical guidelines allows for the possibility to build automatic methods, using pattern recognition techniques, to estimate the proper models, as well as the mathematical models for optimizing the iterative cycle for the continuous improvement of the guidelines. However, to ensure the efficiency of the system, it is necessary to build a probabilistic model of the problem. In this paper, an interactive pattern recognition approach to support professionals in evidence-based medicine is formalized.
Benefits of Selected Physical Exercise Programs in Detention: A Randomized Controlled Study
Authors: Battaglia Claudia , Di Cagno Alessandra , Fiorilli Giovanni , Giombini Arrigo , Fagnani Federica , Borrione Paolo , Marchetti Marco , Pigozzi Fabio
Published: October 2013

The aim of the study was to determine which kind of physical activity could be useful to inmate populations to improve their health status and fitness levels. A repeated measure design was used to evaluate the effects of two different training protocols on subjects in a state of detention, tested pre- and post-experimental protocol.Seventy-five male subjects were enrolled in the studyand randomly allocated to three groups: the cardiovascular plus resistance training protocol group (CRT) (n = 25; mean age 30.9 ± 8.9 years),the high-intensity strength training protocol group (HIST) (n = 25; mean age 33.9 ± 6.8 years), and a control group (C) (n = 25; mean age 32.9 ± 8.9 years) receiving no treatment. All subjects underwent a clinical assessmentandfitness tests. MANOVA revealed significant multivariate effects on group (p < 0.01) and group-training interaction (p < 0.05). CRT protocol resulted the most effective protocol to reach the best outcome in fitness tests. Both CRT and HIST protocols produced significant gains in the functional capacity (cardio-respiratory capacity and cardiovascular disease risk decrease) of incarcerated males. The significant gains obtained in functional capacity reflect the great potential of supervised exercise interventions for improving the health status of incarcerated people.
The Effect of Different Intensities of Treadmill Exercise on Cognitive Function Deficit Following a Severe Controlled Cortical Impact in Rats
Authors: Shen Xiafeng , Li Aiping , Zhang Yuling , Dong XiaoMin , Shan Tian , Wu Yi , Jia Jie , Hu Yongshan
Published: October 2013

Exercise has been proposed for the treatment of traumatic brain injury (TBI). However, the proper intensity of exercise in the early phase following a severe TBI is largely unknown. To compare two different treadmill exercise intensities on the cognitive function following a severe TBI in its early phase, rats experienced a controlled cortical impact (CCI) and were forced to treadmill exercise for 14 days. The results revealed that the rats in the low intensity exercise group had a shorter latency to locate a platform and a significantly better improvement in spatial memory in the Morris water maze (MWM) compared to the control group (p < 0.05). The high intensity exercise group showed a longer latency and a mild improvement in spatial memory compared to the control group rats in the MWM; however, this difference was not statistically significant (p > 0.05). The brain-derived neurotrophic factor (BDNF) and p-CREB protein levels in the contralateral hippocampus were increased significantly in the low intensity exercise group. Our results suggest that 2 weeks of low intensity of treadmill exercise is beneficial for improving cognitive function and increasing hippocampal BDNF expression after a severe TBI in its early phase.
Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors
Authors: Su Bo-Han , Huang Yi-Syuan , Chang Chia-Yun , Tu Yi-Shu , Tseng Yufeng
Published: October 2013

There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar®) and nilotinib (Tasigna®), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.
Enabling Autologous Human Liver Regeneration with Differentiated Adipocyte Stem Cells
Authors: Xu Dan , Nishimura Toshihiko , Zheng Ming , Wu Manhong , Su Hua , Sato Noboru , Lee Gordon , Michie Sara , Glenn Jeffrey , Peltz Gary
Published: October 2013

We developed a novel method for differentiating adipocyte-derived stem cells (ASCs) into hepatocyte-like cells (iHeps). ASCs are cultured as spherical cellular aggregates and are then induced by culture in chemically defined media for a short time period to differentiate into spherical culture iHeps (SCi-Heps). SCi-Heps have many of the in vitro functional properties of mature hepatocytes, and they can stably reconstitute functioning human liver in vivo in a murine model system. Implantation studies demonstrate that SCi-Heps have a very low malignant potential. All human liver regenerative procedures, including ultrasound-guided direct liver implantation, are scalable and appropriate for human clinical use. These methods can be used to achieve the major promise of regenerative medicine. It may now be possible to regenerate human liver using autologous stem cells obtained from a readily accessible tissue.
Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome
Authors: Zorzi Daria , Phan Tammy , Sequi Marco , Lin Yong , Freeman Daniel H. , Cicalese Luca , Rastellini Cristiana
Published: October 2013

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 μm; medium 150–300 μm; small, <150 μm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.
Permissive Schwann Cell Graft/Spinal Cord Interfaces for Axon Regeneration
Authors: Williams Ryan R. , Henao Martha , Pearse Damien D. , Bunge Mary Bartlett
Published: October 2013

The transplantation of autologous Schwann cells (SCs) to repair the injured spinal cord is currently being evaluated in a clinical trial. In support, this study determined properties of spinal cord/SC bridge interfaces that enabled regenerated brainstem axons to cross them, possibly leading to improvement in rat hindlimb movement. Fluid bridges of SCs and Matrigel were placed in complete spinal cord transections. Compared to pregelled bridges of SCs and Matrigel, they improved regeneration of brainstem axons across the rostral interface. The regenerating brainstem axons formed synaptophysin+ bouton-like terminals and contacted MAP2A+ dendrites at the caudal interface. Brainstem axon regeneration was directly associated with glial fibrillary acidic protein (GFAP+) astrocyte processes that elongated into the SC bridge. Electron microscopy revealed that axons, SCs, and astrocytes were enclosed together within tunnels bounded by a continuous basal lamina. Neuroglycan (NG2) expression was associated with these tunnels. One week after injury, the GFAP+ processes coexpressed nestin and brain lipid-binding protein, and the tips of GFAP+/NG2+ processes extended into the bridges together with the regenerating brainstem axons. Both brainstem axon regeneration and number of GFAP+ processes in the bridges correlated with improvement in hindlimb locomotion. Following SCI, astrocytes may enter a reactive state that prohibits axon regeneration. Elongation of astrocyte processes into SC bridges, however, and formation of NG2+ tunnels enable brainstem axon regeneration and improvement in function. It is important for spinal cord repair to define conditions that favor elongation of astrocytes into lesions/transplants.
Mouse Dental Pulp Stem Cells Support Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells in Vitro
Authors: Nakatsuka Ryusuke , Matsuoka Yoshikazu , Uemura Yasushi , Sumide Keisuke , Iwaki Ryuji , Takahashi Masaya , Fujioka Tatsuya , Sasaki Yutaka , Sonoda Yoshiaki
Published: October 2013

It is well documented that specialized mesenchymal stem/stromal cells (MSCs) constitute the hematopoietic stem cell (HSC) niche in the bone marrow (BM), and these MSCs support/maintain the HSCs in an undifferentiated state. A number of studies have demonstrated that BM-derived MSCs (BM-MSCs) can support HSCs in vitro. However, it remains unclear whether nonhematopoietic tissue-derived MSC-like cells, such as dental pulp stem cells (DPSCs), have the ability to support HSCs. In this study, we prospectively isolated DPSCs from mouse mandibular incisors by fluorescence-activated cell sorting (FACS) using BM-MSC markers, such as PDGFRα and Sca-1. The PDGFRα and Sca-1 double-positive DPSCs and BM-MSCs showed similar morphologies and expression patterns of MSC markers. The ability of the DPSCs to support hematopoietic stem/progenitor cells (HSPCs) was then analyzed by an in vitro coculture system. Moreover, their HSC-supporting activity was evaluated by in vivo xenotransplantation assays using NOD/Shi-scid/IL-2Rγcnull (NOG) mice. Interestingly, the DPSCs supported human cord blood (CB)-derived CD34-positive (CD34+), as well as CD34-negative (CD34–), HSCs. The supporting activities of DPSCs for human CB-derived CD34+ and CD34– HSCs were comparable to those of BM-MSCs. The results of the present study demonstrated, for the first time, that prospectively isolated murine PDGFRα and Sca-1 double-positive DPSCs could support primitive human CD34+ and CD34– HSCs in vitro.
Experimental Nonalcoholic Steatohepatitis Induced by Neonatal Streptozotocin Injection and a High-Fat Diet in Rats
Authors: Hsu Huai-Che , Dozen Masaharu , Matsuno Naoto , Obara Hiromichi , Tanaka Ryou , Enosawa Shin
Published: October 2013

Nonalcoholic steatohepatitis (NASH) has become a major concern in clinical hepatology. To elucidate the disease mechanisms and to develop a treatment, the advent of an appropriate experimental model is crucial. Pregnant Sprague–Dawley rats were fed a high-fat diet from gestational day 16. Two days after birth, the neonates were injected subcutaneously with streptozotocin (STZ) (180, 200, or 256 mg/kg). The mothers were fed a high-fat diet during the nursing period. After being weaned (4 weeks of age), the juvenile rats were fed the same high-fat diet. The survival rates at the time of weaning were 25.6% (180 mg/kg STZ), 22.8% (200 mg/kg STZ), and 19.4% (256 mg/kg STZ). The mean body weight of NASH rats was approximately 20% less than that of normal rats. Serum levels of glucose, alanine aminotransferase, and hyaluronic acid increased in NASH rats. Histologically, typical features of steatohepatitis such as ballooning, inflammatory cell infiltration, and perivenular and pericellular fibrosis were observed. In an indocyanine green loading test, the blood half-life was significantly longer in NASH rats (5.04 ± 2.14 vs. 2.72 ± 0.72 min; p < 0.05), which was suggestive of an impaired hepatobiliary transportation function. Concomitantly, biliary ICG concentrations in NASH rats stabilized in a delayed fashion compared with normal rats. In addition, the amount of bile excreted in NASH rats was significantly lower than that in normal rats (4.32 ± 0.83 vs. 7.66 ± 1.05 mg/min; p < 0.01). The rat NASH model presented here mimics the clinical features of the disease and will be a helpful tool for medical and bioscience research.
Development of Canine Models of Type 1 Diabetes with Partial Pancreatectomy and the Administration of Streptozotocin
Authors: Seita Masayuki , Noguchi Hirofumi , Kubota Yasuhiro , Kawamoto Hironobu , Nakaji Shuhei , Kobayashi Naoya , Fujiwara Toshiyoshi
Published: October 2013

We created canine models of type 1 diabetes that were suitable for the assessment of cell therapies, such as islet transplantation and bioartificial pancreas, with low-dose streptozotocin (STZ) injection and partial pancreatectomy. In our model, a 50% pancreatectomy was performed with general anesthesia, followed by systemic injection of 35 mg/kg STZ into a vein of the foreleg. Four weeks after the administration of STZ, the fasting blood glucose level of our model dogs was found to be over 200 mg/dl twice on different days, and we could not detect any canine insulin by the intravenous glucose tolerance test (IVGTT). We therefore diagnosed the dogs to have induced diabetes. Some studies have reported high-dose STZ to be very toxic for both the kidney and liver, and therefore a lower dose is desirable to induce diabetic models without any associated kidney or liver damage. We think that the combination of a partial pancreatectomy can thus make it possible to reduce the dose of STZ, and it is therefore useful for the creation of type 1 diabetes models. We believe that our model is a safe and reliable model for type 1 diabetes in canines to assess the efficacy of pancreas-targeted cell therapies.
APPLICATION OF NEW INFORMATION TECHNOLOGY ON CONCRETE: AN OVERVIEW / NAUJŲ INFORMACINIŲ TECHNOLOGIJŲ NAUDOJIMAS RUOŠIANT BETONĄ. APŽVALGA
Authors: Boukhatem Bakhta , Kenai Said , Tagnit-Hamou Arezki , Ghrici Mohamed
Published: October 2013

The development of information technology provides means for quick access to a wide variety of information and methods of modelling complex systems. Simulation models, databases, decision support systems and artificial intelligence have currently become more accessible. Advances of these techniques continue to impact highly on civil engineering. The aim of this paper is to present recent developments in information technology and their influence on concrete technology. A historical perspective on researches and a review of the application of artificial intelligence techniques on concrete are presented. Development of computer integrated knowledge systems, approach of virtual systems and soft- ware for concrete mix design are also discussed. These systems have greatly affected handling tasks in civil engineering design over the past decade and promise to have revolutionary impacts on the nature of the design tasks in the future. They are considered useful and powerful tools which are able to solve complex problems and represent a scientific challenge in concrete technology.

Santrauka

Vystantis informacinems technologijoms, atsiranda galimybiuų greitai gauti iųvairiausios informacijos ir metoduų, kaip modeliuoti sudėtingas sistemas. Pastaruoju metu paplito imitaciniai modeliai, duomenuų bazės, sprendimuų paramos sistemos ir dirbtinis intelektas. Šiuų metodikuų pažanga statybuų sektoriui ir toliau daro didžiule˛ iųtaka˛. Šiame darbe siekiama pristatyti informaciniuų technologijuų naujienas ir juų iųtaka˛ betono technologijoms. Apžvelgiami ankstesni tyrimai ir dirbtinio intelekto metoduų taikymas ruošiant betona˛. Be to, aptariamas integruotuų kompiuteriniuų žiniuų sistemuų vystymas, virtualiuų sistemuų naudojimas ir programinė iųranga betono mišiniams kurti. Per pastarajių dešimtmetių šios sistemos padarė nemenka˛ iųtaka˛ tam, kaip atliekamos inžinerinio projektavimo užduotys, ir turėtuų paskatinti projektavimo užduoČiuų perversma ateityje. Jos – naudingi ir galingi iųrankiai, leidžiantys spre˛sti sudėtingas problemas, tai mokslinis iššūkis betono technologijuų srityje.
A COMPARATIVE ANALYSIS OF THE PERFORMANCE OF TRADITIONAL CONTRACTING AND DESIGN-BUILD PROCUREMENTS ON CLIENT OBJECTIVES IN NIGERIA / TRADICINIŲ STATYBOS RANGOS IR PROJEKTAVIMO BEI STATYBOS PIRKIMŲ VYKDYMO, ATSIŽVELGIANT Į UŽSAKOVO TIKSLUS, LYGINAMOJI ANALIZĖ NIGERIJOJE
Authors: Ojo Stephen Okunlola , Aina Omotayo , Adeyemi Aderemi Yakeen
Published: October 2013

Client objectives in a building project are to build within the budget and estimated construction period and being satisfied with the quality of the project. The ability of the procurement methods in achieving these objectives does influence the client to choose any to implement the project. The performance of two of such procurement methods: the traditional contracting and design-build against client objectives were determined using data set of 53 traditional contracts and 15 design-build projects gathered through a questionnaire survey administered unto respondents in three locations in Nigeria. Time overrun, cost overrun and clients’ satisfaction with quality standard were used as basis for comparison. Analysis showed that, the mean cost overrun, and time overrun for design-build were 21.4% and 36.8% respectively as compared with 42.6% and 135.6% for traditional contracting projects. As for quality standard, 78% of design-build clients were satisfied with their projects as compared with 51% for traditional contracting. The overall conclusion is that both methods involve overrun but design-build performed better.

Santrauka

Užsakovo, vykdančio statybos projektą tikslai – pastatyti statini neviršijant numatyto biudžeto, statybos trukmės ir būti patenkintam projekto kokybe. Pirkimų metodų galimybė pasiekti šiuos tikslus veikia užsakovo sprendimą kurį iš šių metodų pasirinkti ir igyvendinti. Naudojant 53 tradicinių statybos rangos sutarčių ir 15 projektavimo bei statybos sutarčiųduomenis, surinktus apklausų būdu trijuose Nigerijos regionuose, buvo nustatyti du statybos darbų pirkimo vykdymo bū- dai: tradicinis statybos darbų pirkimas ir projektavimo bei statybos pirkimas, atsižvelgiant į užsakovo tikslus. Statybos trukmės viršijimas, kainos viršijimas, pasitenkinimas atliktų darbų kokybe buvo naudojami kaip palyginimų pagrindas. Atlikta analizė parodė, kad vidutinis trukmės ir kainos viršijimas projektavimo ir statybos sutartyse buvo atitinkamai21,4% ir 36,8%, o tradicinėse statybos rangos sutartyse – 42,6% ir 135,6%. 78% projektavimo bei statybos užsakovųbuvo patenkinti atliktų darbų kokybe, o darbus vykdant pagal tradicines sutartis, patenkintųjųdarbų kokybe buvo 51%. Bendra išvada yra ta, kad abiem metodais buvo viršyta trukmė ir kaina, bet taikant projektavimo bei statybos metodą šie rodikliai yra geresni.
MATHEMATICAL AND FUZZY LOGIC MODELS IN PREDICTION OF GEOLOGICAL AND GEOMECHANICAL PROPERTIES OF ROCK MASS BY EXCAVATION DATA ON UNDERGROUND WORKS / MATEMATINIS IR NERAIŠKIOSIOS LOGIKOS MODELIAI APRAŠANT GEOLOGINES IR GEOMECHANINES UOLIENOS SAVYBES, NAUDOJANT POŽEMINIO KASINĖJIMO DUOMENIS
Authors: Torno Susana , Toraño Javier , Menéndez Mario , Gent Malcolm , Velasco Judith
Published: October 2013

In underground works, the continual consciousness of geological and geomechanical properties of rock mass during drilling, is of major importance to optimize the works and the equipment used. In this paper, the mathematical relationship obtained from tunnel excavations, considering percussion drilling for blasting by a drilling machine and by a tunnel boring machine (TBM) are exposed. These mathematical relationships are useful in the percussion drilling case, to adjust the drilling parameter recorder (DPR) tools, and in the case of TBM to predict the rock mass geomechanical index (RMR). Taking into account the complexity of these mathematical models obtained, as a consequence of the affected variables and their relations, a fuzzy logic model based on parameters accessible to the drilling machine has been used in tricone bit drilling.

Santrauka

Atliekant požeminius uolienų gręžimo darbus ir optimizuojant darbus bei jiems naudojamą įrangą, labai svarbu prognozuoti geologines ir geomechanines uolienos savybes. Šiame darbe pateikiamos gautos matematinės išraiškos, taikant tunelių kasimo duomenis, gautus naudojant smūginio gręžimo ir tunelių gręžimo (TBM) įrangą. Šios matematinės išraiškos yra naudingos smūginio gręžimo metu koreguojant gręžimo parametro fiksavimo (DPR) duomenis, o naudojant TBM įrangą – nustatant uolienos geomechaninį indeksą (RMR). Atsižvelgiant į gautų matematinių modelių kompleksiškumą, t. y. į gautus parametrus ir jų sąryšius, naudotinas neraiškiosios logikos modelis, jungiantis parametrus, tinkamus trigalvio grąžto gręžimo įrangai.