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  This is an Open Access Journal Open Access journal
     ISSN (Online) 2046-1402
     Published by Faculty of 1000 Homepage  [1 journal]
  • Hot topics at the intersection of aging and energetics: Diabetes/insulin
           resistance, Sirtuins, and the Microbiome [v1; indexed,

    • Authors: Dudley W. Lamming
      Abstract: A recent review in F1000Research identified the “top research priorities identified in leading publications” at the interface of Aging and Energetics. The authors identified the ten most-cited papers in each of the years 2010 through 2013, and used these forty papers to identify thematic categories. However, the search methodology used by the authors omitted many high-impact aging manuscripts. Minor modifications in the authors’ search methodology finds that Diabetes/insulin resistance, Sirtuins, and the Microbiome are also top thematic categories.
      PubDate: 2014-10-28
      DOI: 10.12688/f1000research.5625.1
      Issue No: Vol. 3 (2014)
  • Secretomes of apoptotic mononuclear cells ameliorate neurological damage
           in rats with focal ischemia [v2; indexed,]

    • Authors: Patrick Altmann, Michael Mildner, Thomas Haider, Denise Traxler, Lucian Beer, Robin Ristl, Bahar Golabi, Christian Gabriel, Fritz Leutmezer, Hendrik Jan Ankersmit
      Abstract: The pursuit of targeting multiple pathways in the ischemic cascade of cerebral stroke is a promising treatment option. We examined the regenerative potential of conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), rMNCapo sec and hMNCapo sec, in experimental stroke. We performed middle cerebral artery occlusion on Wistar rats and administered apoptotic MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion volumes were determined 48 hours after cerebral ischemia. Neurological evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted to analyze neuroprotective signal-transduction in human primary glia cells and neurons. Neuronal sprouting assays were performed and neurotrophic factors in both hMNCapo sec and rat plasma were quantified using ELISA. Administration of rat as well as human apoptotic MNC-secretomes significantly reduced ischemic lesion volumes by 36% and 37%, respectively. Neurological examinations revealed improvement after stroke in both treatment groups. Co-incubation of human astrocytes, Schwann cells and neurons with hMNCapo sec resulted in activation of several signaling cascades associated with the regulation of cytoprotective gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic factors in hMNCapo sec and rat plasma revealed high levels of brain derived neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes elicit neuroprotective effects on rats that have undergone ischemic stroke.
      PubDate: 2014-10-28
      DOI: 10.12688/f1000research.4219.2
      Issue No: Vol. 3 (2014)
  • Thrombocytosis portends adverse prognostic significance in patients with
           stage II colorectal carcinoma [v2; indexed,]

    • Authors: Tianhua Guo, Marcin Krzystanek, Zoltan Szallasi, Arpad Szallasi
      Abstract: Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.
      PubDate: 2014-10-20
      DOI: 10.12688/f1000research.4856.2
      Issue No: Vol. 3 (2014)
  • Late cardiac sodium current can be assessed using automated patch-clamp
           [v1; indexed,]

    • Authors: Morgan Chevalier, Bogdan Amuzescu, Vaibhavkumar Gawali, Hannes Todt, Thomas Knott, Olaf Scheel, Hugues Abriel
      Abstract: The cardiac late Na+ current is generated by a small fraction of voltage-dependent Na+ channels that undergo a conformational change to a burst-gating mode, with repeated openings and closures during the action potential (AP) plateau. Its magnitude can be augmented by inactivation-defective mutations, myocardial ischemia, or prolonged exposure to chemical compounds leading to drug-induced (di)-long QT syndrome, and results in an increased susceptibility to cardiac arrhythmias. Using CytoPatch™ 2 automated patch-clamp equipment, we performed whole-cell recordings in HEK293 cells stably expressing human Nav1.5, and measured the late Na+ component as average current over the last 100 ms of 300 ms depolarizing pulses to -10 mV from a holding potential of -100 mV, with a repetition frequency of 0.33 Hz. Averaged values in different steady-state experimental conditions were further corrected by the subtraction of current average during the application of tetrodotoxin (TTX) 30 μM. We show that ranolazine at 10 and 30 μM in 3 min applications reduced the late Na+ current to 75.0 ± 2.7% (mean ± SEM, n = 17) and 58.4 ± 3.5% (n = 18) of initial levels, respectively, while a 5 min application of veratridine 1 μM resulted in a reversible current increase to 269.1 ± 16.1% (n = 28) of initial values. Using fluctuation analysis, we observed that ranolazine 30 μM decreased mean open probability p from 0.6 to 0.38 without modifying the number of active channels n, while veratridine 1 μM increased n 2.5-fold without changing p. In human iPSC-derived cardiomyocytes, veratridine 1 μM reversibly increased APD90 2.12 ± 0.41-fold (mean ± SEM, n = 6). This effect is attributable to inactivation removal in Nav1.5 channels, since significant inhibitory effects on hERG current were detected at higher concentrations in hERG-expressing HEK293 cells, with a 28.9 ± 6.0% inhibition (mean ± SD, n = 10) with 50 μM veratridine.      
      PubDate: 2014-10-16
      DOI: 10.12688/f1000research.5544.1
      Issue No: Vol. 3 (2014)
  • Observations on spiny dogfish (Squalus acanthias) captured in late spring
           in a North Carolina estuary [v2; indexed,]

    • Authors: Charles Bangley, Roger Rulifson
      Abstract: Five spiny dogfish were captured in early-mid May during gillnet and longline sampling targeting juvenile coastal sharks in inshore North Carolina waters.  Dogfish captures were made within Back Sound and Core Sound, North Carolina. All dogfish were females measuring 849-905 mm total length, well over the size at 50% maturity. Dogfish were caught at stations 1.8-2.7 m in depth, with temperatures 22.9-24.2 °C, 32.8-33.4 ppt salinity, and 6.9-8.0 mg/L dissolved oxygen. These observations are among the latest in the spring for spiny dogfish in the southeastern U.S. and occurred at higher temperatures than previously recorded for this species.  It is unclear whether late-occurring spiny dogfish in this area represent a cryptic late-migrating or resident segment of the Northwest Atlantic population.
      PubDate: 2014-10-13
      DOI: 10.12688/f1000research.4890.2
      Issue No: Vol. 3 (2014)
  • Predictive factors for difficult mask ventilation in the obese surgical
           population [v1; indexed,]

    • Authors: Davide Cattano, Anastasia Katsiampoura, Ruggero M. Corso, Peter V. Killoran, Chunyan Cai, Carin A. Hagberg
      Abstract: Background Difficult Mask Ventilation (DMV), is a situation in which it is impossible for an unassisted anesthesiologist to maintain oxygen saturation >90% using 100% oxygen and positive pressure ventilation to prevent or reverse signs of inadequate ventilation during mask ventilation.  The incidence varies from 0.08 – 15%. Patient-related anatomical features are by far the most significant cause.  We analyzed data from an obese surgical population (BMI> 30 kg/m2) to identify specific risk and predictive factors for DMV. Methods Five hundred and fifty seven obese patients were identified from a database of 1399 cases associated with preoperative airway examinations where mask ventilation was attempted. Assessment of mask ventilation in this group was stratified by a severity score (0-3), and a step-wise selection method was used to identify independent predictors.  The area under the curve of the receiver-operating-characteristic was then used to evaluate the model’s predictive value. Adjusted odds ratios and their 95% confidence intervals were also calculated. Results DMV was observed in 80/557 (14%) patients. Three independent predictive factors for DMV in obese patients were identified: age 49 years, short neck, and neck circumference  43 cm. In the current study th sensitivity for one factor is 0.90 with a specificity 0.35. However, the specificity increased to 0.80 with inclusion of more than one factor. Conclusion According to the current investigation, the three predictive factors are strongly associated with DMV in obese patients. Each independent risk factor alone provides a good screening for DMV and two factors substantially improve specificity. Based on our analysis, we speculate that the absence of at least 2 of the factors we identified might have a significant negative predictive value and can reasonably exclude DMV, with a negative likelihood ratio 0.81.
      PubDate: 2014-10-09
      DOI: 10.12688/f1000research.5471.1
      Issue No: Vol. 3 (2014)
  • Estrogen as Jekyll and Hyde: regulation of cell death [v2; indexed,

    • Authors: Wen Zhou, Xiaoxia Zhu
      Abstract: Sustained estrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. Unexpectedly, physiological level of estrogen together with a novel IKKα inhibitor BAY11-7082 could effectively induce cell apoptosis in ER-positive breast cancer cells, suggesting combining estrogen with IKKα inhibition may be beneficial for breast cancer patients. This opinion article touches upon the dual role estrogen played in inducing cancer cell death and asks whether use of estrogen in combination with IKKα-targeted therapy would be possible reconsider the newly identified crosstalk between ER and NFκB pathway which can be utilized to switch the effects of estrogen on cell death.
      PubDate: 2014-09-29
      DOI: 10.12688/f1000research.4753.2
      Issue No: Vol. 3 (2014)
  • [18F]-T807 tauopathy PET imaging in chronic traumatic encephalopathy [v1;

    • Authors: Sam Gandy, Steven T. DeKosky
      Abstract: A new molecular ligand for positron emission tomography (PET) of the human brain, [18F]-T807, is under investigation for the antemortem detection of pathological neurofibrillary aggregates, which are evidence of neurofibrillary tangle (NFT) diseases, also known as tauopathies. Repetitive mild traumatic brain injuries in athletes and battlefield veterans are associated with one such tauopathy, known as chronic traumatic encephalopathy (CTE). In a recent case report, a former NFL player with clinically probable CTE and a concurrent Progressive Supranuclear Palsy (PSP) –like syndrome was studied using [18F]-T807. The interpretation of this player’s [18F]-T807 PET imaging was complicated by the overlap of tracer uptake in brain regions involved in CTE and PSP with regions associated with either nonspecific [18F]-T807 ligand binding or “aging-associated” binding of [18F]-T807 to authentic tauopathy known to be associated with aging and disease severity (i.e., NFT in the mesial temporal lobe). The implications of these data for the utility of [18F]-T807 in the pre-mortem detection of CTE are summarized.
      PubDate: 2014-09-29
      DOI: 10.12688/f1000research.5372.1
      Issue No: Vol. 3 (2014)
  • A novel mouse model of creatine transporter deficiency [v1; indexed,

    • Authors: Laura Baroncelli, Maria Grazia Alessandrì, Jonida Tola, Elena Putignano, Martina Migliore, Elena Amendola, Cornelius Gross, Vincenzo Leuzzi, Giovanni Cioni, Tommaso Pizzorusso
      Abstract: Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement  and behavioral disturbances, language and speech impairment ( OMIM #300352). CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.
      PubDate: 2014-09-29
      DOI: 10.12688/f1000research.5369.1
      Issue No: Vol. 3 (2014)
  • Pandemic 2009 Influenza A (H1N1) virus infection in cancer and
           hematopoietic stem cell transplant recipients; a multicenter observational
           study. [v1; indexed,]

    • Authors: Maria Cecilia Dignani, Patricia Costantini, Claudia Salgueira, Rosana Jordán, Graciela Guerrini, Alejandra Valledor, Fabián Herrera, Andrea Nenna, Claudia Mora, Inés Roccia-Rossi, Daniel Stecher, Edith Carbone, Ana Laborde, Ernesto Efron, Javier Altclas, Aníbal Calmaggi, José Cozzi
      Abstract: Background: During March 2009 a novel Influenza A virus emerged in Mexico. We describe the clinical picture of the pandemic Influenza A (H1N1) Influenza in cancer patients during the 2009 influenza season. Methods: Twelve centers participated in a multicenter retrospective observational study of cancer patients with confirmed infection with the 2009 H1N1 Influenza A virus (influenza-like illness or pneumonia plus positive PCR for the 2009 H1N1 Influenza A virus  in respiratory secretions). Clinical data were obtained by retrospective chart review and analyzed.  Results: From May to August 2009, data of 65 patients were collected. Median age was 51 years, 57 % of the patients were female. Most patients (47) had onco-hematological cancers and 18 had solid tumors. Cancer treatment mainly consisted of chemotherapy (46), or stem cell transplantation (SCT) (16). Only 19 of 64 patients had received the 2009 seasonal Influenza vaccine. Clinical presentation included pneumonia (43) and upper respiratory tract infection (22). Forty five of 58 ambulatory patients were admitted. Mechanical ventilation was required in 12 patients (18%). Treatment included oseltamivir monotherapy or in combination with amantadine for a median of 7 days. The global 30-day mortality rate was 18%. All 12 deaths were among the non-vaccinated patients. No deaths were observed among the 19 vaccinated patients. Oxygen saturation
      PubDate: 2014-09-12
      DOI: 10.12688/f1000research.5251.1
      Issue No: Vol. 3 (2014)
  • Case Report: Primary Leiomyosarcoma of the breast with unusual metastasis
           to the femur [v1; indexed,]

    • Authors: Evgeniya Sokolovskaya, Zheng Liu, Kelly Weintraub, Arpad Szallasi, Yasmeen Shariff
      Abstract: With less than 40 cases reported, primary leiomyosarcoma is an extremely rare form of breast cancer (less than 0.0006% of cases) with unpredictable biological behavior that usually presents as a slow growing, mobile mass in middle age women. Most cases are low-grade and are cured by complete excision with wide margins. After surgical resection, late local recurrence and distant hematogenous metastasis to lungs and liver is, however, well-documented. To the best of our knowledge, bone metastasis has never been reported. Here we present a case of primary leiomyosarcoma of the breast metastatic to the femur.
      PubDate: 2014-09-04
      DOI: 10.12688/f1000research.5213.1
      Issue No: Vol. 3 (2014)
  • EpiCollect+: linking smartphones to web applications for complex data
           collection projects [v1; indexed,]

    • Authors: David M. Aanensen, Derek M. Huntley, Mirko Menegazzo, Chris I. Powell, Brian G. Spratt
      Abstract: Previously, we have described the development of the generic mobile phone data gathering tool, EpiCollect, and an associated web application, providing two-way communication between multiple data gatherers and a project database. This software only allows data collection on the phone using a single questionnaire form that is tailored to the needs of the user (including a single GPS point and photo per entry), whereas many applications require a more complex structure, allowing users to link a series of forms in a linear or branching hierarchy, along with the addition of any number of media types accessible from smartphones and/or tablet devices (e.g., GPS, photos, videos, sound clips and barcode scanning). A much enhanced version of EpiCollect has been developed (EpiCollect+). The individual data collection forms in EpiCollect+ provide more design complexity than the single form used in EpiCollect, and the software allows the generation of complex data collection projects through the ability to link many forms together in a linear (or branching) hierarchy. Furthermore, EpiCollect+ allows the collection of multiple media types as well as standard text fields, increased data validation and form logic. The entire process of setting up a complex mobile phone data collection project to the specification of a user (project and form definitions) can be undertaken at the EpiCollect+ website using a simple ‘drag and drop’ procedure, with visualisation of the data gathered using Google Maps and charts at the project website. EpiCollect+ is suitable for situations where multiple users transmit complex data by mobile phone (or other Android devices) to a single project web database and is already being used for a range of field projects, particularly public health projects in sub-Saharan Africa. However, many uses can be envisaged from education, ecology and epidemiology to citizen science.
      PubDate: 2014-08-20
      DOI: 10.12688/f1000research.4702.1
      Issue No: Vol. 3 (2014)
  • Current treatment of early breast cancer: adjuvant and neoadjuvant therapy
           [v1; indexed,]

    • Authors: Elizabeth Miller, Hee Jin Lee, Amriti Lulla, Liz Hernandez, Prashanth Gokare, Bora Lim
      Abstract: Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.
      PubDate: 2014-08-19
      DOI: 10.12688/f1000research.4340.1
      Issue No: Vol. 3 (2014)
  • FALCON: a software package for analysis of nestedness in bipartite
           networks [v1; indexed,]

    • Authors: Stephen J. Beckett, Chris A. Boulton, Hywel T. P. Williams
      Abstract: Nestedness is a statistical measure used to interpret bipartite interaction data in several ecological and evolutionary contexts, e.g. biogeography (species-site relationships) and species interactions (plant-pollinator and host-parasite networks). Multiple methods have been used to evaluate nestedness, which differ in how the metrics for nestedness are determined. Furthermore, several different null models have been used to calculate statistical significance of nestedness scores. The profusion of measures and null models, many of which give conflicting results, is problematic for comparison of nestedness across different studies. We developed the FALCON software package to allow easy and efficient comparison of nestedness scores and statistical significances for a given input network, using a selection of the more popular measures and null models from the current literature. FALCON currently includes six measures and five null models for nestedness in binary networks, and two measures and four null models for nestedness in weighted networks. The FALCON software is designed to be efficient and easy to use. FALCON code is offered in three languages (R, MATLAB, Octave) and is designed to be modular and extensible, enabling users to easily expand its functionality by adding further measures and null models. FALCON provides a robust methodology for comparing the strength and significance of nestedness in a given bipartite network using multiple measures and null models. It includes an “adaptive ensemble” method to reduce undersampling of the null distribution when calculating statistical significance. It can work with binary or weighted input networks. FALCON is a response to the proliferation of different nestedness measures and associated null models in the literature. It allows easy and efficient calculation of nestedness scores and statistical significances using different methods, enabling comparison of results from different studies and thereby supporting theoretical study of the causes and implications of nestedness in different biological contexts.
      PubDate: 2014-08-06
      DOI: 10.12688/f1000research.4831.1
      Issue No: Vol. 3 (2014)
  • Developing sustainable software solutions for bioinformatics by the
           “Butterfly” paradigm [v2; indexed,]

    • Authors: Zeeshan Ahmed, Saman Zeeshan, Thomas Dandekar
      Abstract: Software design and sustainable software engineering are essential for the long-term development of bioinformatics software. Typical challenges in an academic environment are short-term contracts, island solutions, pragmatic approaches and loose documentation. Upcoming new challenges are big data, complex data sets, software compatibility and rapid changes in data representation. Our approach to cope with these challenges consists of iterative intertwined cycles of development (“Butterfly” paradigm) for key steps in scientific software engineering. User feedback is valued as well as software planning in a sustainable and interoperable way. Tool usage should be easy and intuitive. A middleware supports a user-friendly Graphical User Interface (GUI) as well as a database/tool development independently. We validated the approach of our own software development and compared the different design paradigms in various software solutions.
      PubDate: 2014-08-01
      DOI: 10.12688/f1000research.3681.2
      Issue No: Vol. 3 (2014)
  • Development and use of the Cytoscape app GFD-Net for measuring semantic
           dissimilarity of gene networks [v1; indexed,]

    • Authors: Juan J. Diaz-Montana, Norberto Diaz-Diaz
      Abstract: Gene networks are one of the main computational models used to study the interaction between different elements during biological processes being widely used to represent gene–gene, or protein–protein interaction complexes. We present GFD-Net, a Cytoscape app for visualizing and analyzing the functional dissimilarity of gene networks.
      PubDate: 2014-07-01
      DOI: 10.12688/f1000research.4573.1
      Issue No: Vol. 3 (2014)
  • Dentin reactions to caries are misinterpreted by histological “gold
           standards” [v1; indexed,]

    • Authors: Priscila Florentino Silva, Danilo Augusto de Holanda Ferreira, Kássia Regina Simões Meira, Franklin Delano Soares Forte, Ana Maria Barros Chaves, Frederico Barbosa de Sousa
      Abstract: Dentin reactions to caries, crucial for pathogenesis and for the determination of the severity of caries lesions, are believed to be reasonably detected by stereomicroscopy (SM) and polarized light microscopy in quinoline (PLMQ), but accuracies are not available. Here, stereomicroscopy of wet (SW) and dry (SD) ground sections of natural occlusal caries lesions resulted in moderate (0.7, for normal dentin) and low accuracies (< 0.6, for carious and sclerotic dentin) as validated by contrast-corrected microradiography. Accuracies of PLMQ were moderate for both normal (0.71) and carious dentin (0.71). The hypothesis that detection of dentin reactions by SM and PLMQ would be influenced by the contrast quality of micrographic images was rejected. Dentin reactions were scored by SW, SD, PLMQ, and three types of microradiographic images with varying contrast qualities and each technique was compared against the one that resulted in the highest number of scores for each dentin reaction. Large differences resulted, mainly related to the detection of sclerotic dentin by both SW and SD, and normal and carious dentin by PLMQ. It is concluded that contrast-corrected microradiography should be preferred as the gold standard and SM and PLMQ should be avoided, but the relationship of PLMQ with dentin mineralization deserves further investigation.
      PubDate: 2014-01-16
      DOI: 10.12688/f1000research.3-13.v1
      Issue No: Vol. 3 (2014)
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