Miracle-dz/UniFAR-FTUs huggingface dataset:
Controlled release of vascular endothelial growth factor from spray‐dried alginate microparticles in collagen–hydroxyapatite scaffolds for promoting vascularization and bone repair

A major limitation with current tissue‐engineering approaches is creating functionally vascularized constructs that can successfully integrate with the host; this often leads to implant failure, due to avascular necrosis. In order to overcome this, the objective of the present work was to develop a method to incorporate growth factor‐eluting alginate microparticles (MPs) into freeze‐dried, collagen‐based scaffolds. A collagen–hydroxyapatite (CHA) scaffold, previously optimized for bone regeneration, was functionalized for the sustained delivery of an angiogenic growth factor, vascular endothelial growth factor (VEGF), with the aim of facilitating angiogenesis and enhancing bone regeneration. VEGF was initially encapsulated in alginate MPs by spray‐drying, producing particles of < 10 µm in diameter. This process was found to effectively encapsulate and control VEGF release while maintaining its stability and bioactivity post‐processing. These VEGF‐MPs were then incorporated into CHA scaffolds, leading to homogeneous distribution throughout the interconnected scaffold pore structure. The scaffolds were capable of sustained release of bioactive VEGF for up to 35 days, which was proficient at increasing tubule formation by endothelial cells in vitro. When implanted in vivo in a rat calvarial defect model, this scaffold enhanced vessel formation, resulting in increased bone regeneration compared to empty‐defect and VEGF‐free scaffolds. This biologically functionalized scaffold, composed entirely of natural‐based materials, may offer an ideal platform to promote angiogenesis and tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd.
Characterization of putative haematopoietic cells from bovine yolk sac

The yolk sac is an extra‐embryonic membrane that plays an important role in early embryonic survival. It is the production site for blood cells during embryonic mammalian development and is a likely source of stem cells. The aim of this study was to identify and characterize the putative haematopoietic cells from the yolk sac of bovine embryos at different stages of gestation. The yolk sac regresses according to gestational age and embryos are characterized into groups (I–V) according to the crown–rump measurement. Groups I–III survived in culture longer and exhibited the formation of cell clusters, whereas groups IV and V could not be maintained in culture for an extended period of time. Flow‐cytometry analysis revealed that groups I–III had similar characteristics, including high expression levels of the haematopoietic markers CD34, CD90 and CD117. In groups IV and V, decreases were observed in the expression levels of CD117 and CD34. Cells were found to be capable of survival post‐cryopreservation and exhibited varying abilities to form colonies in a methylcellulose matrix, depending on gestational age. Cytological analysis revealed the presence of blood cells (lymphocytes and monocytes). Quantitative PCR analysis demonstrated the presence of the haematopoietic progenitor genes GATA3 and LMO2, but not RUNX1. Thus, we have successfully isolated and characterized haematopoietic cells from the bovine embryo yolk sac at varying gestational ages. This study is crucial for the understanding of the development of the haematopoietic system and the embryonic function of this organ. Copyright © 2015 John Wiley & Sons, Ltd.
A Radiocarbon Date of Peat from James Bay in Quebec.

sugars are approximately equal to that of the carbon fed. Figure 2 shows the radioautographs obtained from the ethanol extracts. The activity first appeared in sucrose and only later in fructose and glucose. This is in agreement with the results obtained by Calvin and Benson (3). The fructose and glucose are in approximately equal amounts and contain about the same total activity. Hydrolysis of sucrose revealed that the specific activity of the glucose and fructose moieties are about the same. This suggests that the Crrr glucose and fructose are fontird by sucrose hy-
Arthroscopic Suture Anchor Repair of the Lateral Ligament Ankle Complex

Background: Operative treatment of mechanical ankle instability is indicated for patients with multiple sprains and continued episodes of instability. Open repair of the lateral ankle ligaments involves exposure of the attenuated ligaments and advancement back to their anatomic insertions on the fibula using bone tunnels or suture implants. Hypothesis: Open and arthroscopic fixation are equal in strength to failure for anatomic Broström repair. Study Design: Controlled laboratory study. Methods: Seven matched pairs of human cadaveric ankle specimens were randomized into 2 groups of anatomic Broström repair: open or arthroscopic. The calcaneofibular ligament and anterior talofibular ligament were excised from their origin on the fibula. In the open repair group, 2 suture anchors were used to reattach the ligaments to their anatomic origins. In the arthroscopic repair group, identical suture anchors were used for repair via an arthroscopic technique. The ligaments were cyclically loaded 20 times and then tested to failure. Torque to failure, degrees to failure, initial stiffness, and working stiffness were measured. A matched-pair analysis was performed. Power analysis of 0.8 demonstrated that 7 pairs needed to show a difference of 30%, with a 15% standard error at a significance level of α = . 05. Results: There was no difference in the degrees to failure, torque to failure, or stiffness for the repaired ligament complex. Nine of 14 specimens failed at the suture anchor. Conclusion: There is no statistical difference in strength or stiffness of a traditional open repair as compared with an arthroscopic anatomic repair of the lateral ligaments of the ankle. Clinical Relevance: An arthroscopic technique can be considered for lateral ligament stabilization in patients with mild to moderate mechanical instability.
In vitro chondrogenic commitment of human Wharton's jelly stem cells by co‐culture with human articular chondrocytes

Wharton's jelly stem cells (WJSCs) are a potential source of transplantable stem cells in cartilage‐regenerative strategies, due to their highly proliferative and multilineage differentiation capacity. We hypothesized that a non‐direct co‐culture system with human articular chondrocytes (hACs) could enhance the potential chondrogenic phenotype of hWJSCs during the expansion phase compared to those expanded in monoculture conditions. Primary hWJSCs were cultured in the bottom of a multiwell plate separated by a porous transwell membrane insert seeded with hACs. No statistically significant differences in hWJSCs duplication number were observed under either of the culture conditions during the expansion phase. hWJSCs under co‐culture conditions show upregulations of collagen type I and II, COMP, TGFβ1 and aggrecan, as well as of the main cartilage transcription factor, SOX9, when compared to those cultured in the absence of chondrocytes. Chondrogenic differentiation of hWJSCs, previously expanded in co‐culture and monoculture conditions, was evaluated for each cellular passage using the micromass culture model. Cells expanded in co‐culture showed higher accumulation of glycosaminoglycans (GAGs) compared to cells in monoculture, and immunohistochemistry for localization of collagen type I revealed a strong detection signal when hWJSCs were expanded under monoculture conditions. In contrast, type II collagen was detected when cells were expanded under co‐culture conditions, where numerous round‐shaped cell clusters were observed. Using a micromass differentiation model, hWJSCs, previously exposed to soluble factors secreted by hACs, were able to express higher levels of chondrogenic genes with deposition of cartilage extracellular matrix components, suggesting their use as an alternative cell source for treating degenerated cartilage. Copyright © 2015 John Wiley & Sons, Ltd.
A maximum entropy approach for vietnamese word segmentation

In this paper, we introduce a new approach for Vietnamese Word Segmentation. The word segmentation problem is restated into the morpho-syllable position-in-word (PIW) tagging problem. We used the Maximum Entropy with the Generalized Iterative Scaling (GIS) to train on the annotated corpora. The result of the training process was used to tag all the morpho-syllables of the input sentence. With the output sentence tagged, we can convert it into a segmented sentence for evaluation. The results on a lot of tagged-corpora show that this approach is suitable for Vietnamese Word Segmentation. The performance achieves precision and recall rates of 94.87% and 94.08% respectively, and the F-measure of 94.44%. Index Terms—word segmentation, maximum entropy
Human cell culture process capability: a comparison of manual and automated production

Cell culture is one of the critical bioprocessing steps required to generate sufficient human‐derived cellular material for most cell‐based therapeutic applications in regenerative medicine. Automated cell expansion is fundamental to the development of scaled, robust and cost effective commercial production processes for cell‐based therapeutic products. This paper describes the first application of process capability analysis to establish and compare the short‐term process capability of manual and automated processes for the in vitro expansion of a selected anchorage‐dependent cell line. Estimates of the process capability indices (Cp, Cpk) have been used to assess the ability of both processes to consistently meet the requirements for a selected productivity output and to direct process improvement activities. Point estimates of Cp and Cpk show that the manual process has poor capability (Cp = 0.55, Cpk = 0.26) compared to the automated process (Cp = 1.32, Cpk = 0.25), resulting from excess variability. Comparison of point estimates, which shows that Cpk < Cp, indicates that the automated process mean was off‐centre and that intervention is required to adjust the location of the process mean. A process improvement strategy involving an adjustment to the automated process settings has demonstrated in principle that the process mean can be shifted closer to the centre of the specification to achieve an estimated seven‐fold improvement in process performance. In practice, the 90% confidence bound estimate of Cp (Cp = 0.90) indicates that that once the process is centred within the specification, a further reduction of process variation is required to attain an automated process with the desired minimum capability requirement. Copyright © 2009 John Wiley & Sons, Ltd.
Electrospun fibrinogen–PLA nanofibres for vascular tissue engineering

Here we report on the development of a new type of hybrid fibrinogen–polylactic acid (FBG–PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate‐like morphology with multiple projections. The well‐developed focal adhesion complexes suggested a successful cellular interaction. However, time‐lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time‐lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization. Copyright © 2016 John Wiley & Sons, Ltd.
Combinatorial therapy with three‐dimensionally cultured adipose‐derived stromal cells and self‐assembling peptides to enhance angiogenesis and preserve cardiac function in infarcted hearts

Even though stem cell therapy is a promising angiogenic strategy to treat ischaemic diseases, including myocardial infarction (MI), therapeutic efficacy is limited by low survival and retention of transplanted cells in ischaemic tissues. In addition, therapeutic angiogenesis depends on stimulating host angiogenesis with paracrine factors released by transplanted cells rather than on direct blood vessel formation by transplanted cells. In the present study, to overcome these limitations and to enhance the therapeutic efficacy of MI treatment, combinatorial therapy with three‐dimensional cell masses (3DCMs) and self‐assembling peptides (SAPs) was tested in a rat MI model. Spheroid‐type 3DCMs, which are vascular differentiation‐induced cells, were prepared by culturing human adipose‐derived stromal cells on a fibroblast growth factor‐immobilized surface. The SAPs were used as the carrier material to increase engraftment of transplanted cells. After coronary artery ligation, 3DCMs were combined with SAPs and were transplanted into ischaemic lesions. The therapeutic potential was evaluated 4 weeks after treatment. By combining 3DCMs and SAPs, survival and retention of transplanted cells increased threefold when compared with treatment with 3DCMs alone and transplanted cells established vascular networks in infarcted hearts. In addition, the size of the infarct in the 3DCM + SAP group was reduced to 6.09 ± 2.83% by the promotion of host angiogenesis and cardiac function was preserved, as demonstrated by a 54.25 ± 4.42% increase in the ejection fraction. This study indicates that combinatorial therapy with 3DCM and SAPs could be a promising strategy for therapeutic angiogenesis to treat MI. Copyright © 2016 John Wiley & Sons, Ltd.
An effective GRASP+VND metaheuristic for the k-Minimum Latency Problem

Minimum Latency Problem (MLP) is a class of NP-hard combinatorial optimization problems which has many practical applications. In this paper, a general variant of MLP, also known as k-MLP is introduced. In k — MLP problem, the cost of objective function becomes the sum of waiting times at sites and k vehicles cover one of k routes. The goal is to find the order of customer visits that minimizes the sum of waiting time. The problem is a natural and practical extension of the k =1 case. In our work, we propose the first meta-heuristic algorithm which is mainly based on the principles of Greedy Randomized Adaptive Search Procedure (GRASP) and Variable Neighborhood Descent (VND) to solve the problem. The GRASP is used to build an initial solution which is good enough in construction phase. In a cooperative way, the VND is employed to generate diverse neighborhoods in improvement phase, therefore, it can prevent the search to escape from local optimal. In addition, we also introduce a new novel neighborhoods' structure in VND. In order to evaluate the performance of our algorithm, we also discuss an upper bound and a lower bound of the optimal solution. Extensive numerical experiments on benchmark instances show that our algorithm finds good-quality solutions fast, even for large instances which are up to 1200 customers.
The Carbon Dioxide Exchange

Understanding how carbon dioxide cycles between land and atmosphere is key to developing better climate models. One key to accurately predicting future levels of atmospheric carbon dioxide (CO2) is understanding how land and atmosphere exchange CO2. Each year, photosynthesizing land plants remove (fix) one in eight molecules of atmospheric CO2, and respiring land plants and soil organisms return a similar number. This exchange determines whether terrestrial ecosystems are a net carbon sink or source. Two papers in this issue contribute to understanding the land-atmosphere exchange by elegantly analyzing rich data sets on CO2 fluxes from a global network of monitoring sites. On page 834, Beer et al. (1) estimate total annual terrestrial gross primary production (GPP) in an approach more solidly based on data than previous simple approximations. On page 838, Mahecha et al. (2) assess how ecosystem respiration (R) is related to temperature over short (week-to-month) and long (annual) time scales, and find a potentially important but difficult-to-interpret relationship.
Valproic acid enhances the neural differentiation of human placenta derived‐mesenchymal stem cells in vitro

Mesenchymal stem cells (MSCs) are known to express a wide range of markers belonging to all the three lineages: mesodermal, ectodermal and endodermal. Therefore, the possibility of their transdifferentiation towards a neural lineage has been an aspect of active research. In the present study, MSCs were isolated from human placental tissue (P‐MSC) and subjected them to neural differentiation. It was found that the P‐MSCs differentiated towards neural lineage in appropriate differentiation conditions. However, when a histone deacetylase (HDAC) inhibitor – valproic acid (VPA) – was incorporated in the medium, there was a further increase in their neural differentiation potential. The increase in the number of neurites and neural lineage specific markers was notable. The VPA‐treated cells showed a significantly elevated membrane potential compared with the cells grown in only differentiation medium. When the molecular mechanism was studied, the enhancement in the neuronal lineage specification was caused by the inhibition of bone morphogenetic protein (BMP) 2 and an increase in BMP4 under both conditions. The target of VPA (HDAC2) was reduced in the VPA set, whereas HDAC1 remained unchanged. Concurrent reduction in the levels of Stat3 was observed, leading to an upregulation of βIII tubulin, which is a neuronal lineage‐specific marker. The components of Notch signalling (i.e. decreased notch 1 and increased notch 3) also supported differentiation towards the neuronal lineage. Thus, the VPA treated P‐MSCs can serve as an alternative source for deriving neural cells for use in both research and in clinics. Copyright © 2016 John Wiley & Sons, Ltd.
Image super resolution by sparse linear regression and iterative back projection

This paper presents a method which focus on the increase of visual quality of SR image reconstructed from input low resolution image. Similar to the framework as exploited in [1], a modified algorithm is developed which is based on sparse linear regression and iterative back projection. Different from the techniques used in [1] [6], a feature sign search algorithm [17] is used to find the relevant features of the regression function under a priori assumption. Furthermore, a modified Gaussian high pass filter is additionally used for the refinement of the initial reconstructed SR image through iterative back-projection technique to reduce visual artifacts. Experimental results conclude that this modified approach achieves better quality of reconstructed SR images than the other similar SR methods.
A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells: a promising tool for vascular tissue regeneration

Cardiovascular diseases represent a major global health burden, with high rates of mortality and morbidity. Autologous grafts are commonly used to replace damaged or failing blood vessels; however, such approaches are hampered by the scarcity of suitable graft tissue, donor site morbidity and poor long‐term stability. Tissue engineering has been investigated as a means by which exogenous vessel grafts can be produced, with varying levels of success to date, a result of mismatched mechanical properties of these vessel substitutes and inadequate ex vivo vessel tissue genesis. In this work, we describe the development of a novel multifunctional dual‐phase (air/aqueous) bioreactor, designed to both rotate and perfuse small‐diameter tubular scaffolds and encourage enhanced tissue genesis throughout such scaffolds. Within this novel dynamic culture system, an elastomeric nanofibrous, microporous composite tubular scaffold, composed of poly(caprolactone) and acrylated poly(lactide‐co‐trimethylene‐carbonate) and with mechanical properties approaching those of native vessels, was seeded with human mesenchymal stem cells (hMSCs) and cultured for up to 14 days in inductive (smooth muscle) media. This scaffold/bioreactor combination provided a dynamic culture environment that enhanced (compared with static controls) scaffold colonization, cell growth, extracellular matrix deposition and in situ differentiation of the hMSCs into mature smooth muscle cells, representing a concrete step towards our goal of creating a mature ex vivo vascular tissue for implantation. Copyright © 2016 John Wiley & Sons, Ltd.
Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation

The eukaryote maintenance DNA methyltransferase discriminates against de novo CpG methylation sites. Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC–BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.
Ethics of clinical genetics: The spirit of the profession and trials of suitability from 1970 to 2000

As research on and applications of human genetics expanded remarkably during the 1990s, claims were increasingly raised that genetics and its applications should also be considered from an ethical viewpoint. Here medical ethics is the subject of sociological analysis. The paper examines how medical ethics gradually became part of the argumentation and practices of genetic counselling and screening during three decades (1970-2000) by analysing screening and counselling projects and physicians' argumentation in Finland. Medical ethics is analysed as part of a network of experts, regulations and mores, and is regarded as an ongoing process embedded in the processes of medicine, the healthcare system and legislation. It appears that there were two main forms of medical ethics. First, there was the medical ethics that refers to the age-old ways of proper practising of medicine and helping the suffering patient, i.e. the spirit inspiring the profession. Second, during recent decades, medical ethics gradually became expressed in more operationalized and formalized forms, examples of which are codes of ethics, the ethics committees governing medical research and the psychosocial questionnaire studies examining clients' satisfaction and approval. The present paper analyses the medically and morally complicated circumstances in which new formulations of ethics as well as the revival of old foundational medical ethics gained ground.