Miracle-dz/UniFAR-FTUs huggingface dataset:
Exosomes From Human CD34+ Stem Cells Mediate Their Proangiogenic Paracrine Activity

Rationale: Transplantation of human CD34+ stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34+ cell transplantation. Objective: Our objective was to investigate the mechanism of CD34+ stem cell–induced proangiogenic paracrine effects and to examine if exosomes, a component of paracrine secretion, are involved. Methods and Results: Exosomes collected from the conditioned media of mobilized human CD34+ cells had the characteristic size (40 to 90 nm; determined by dynamic light scattering), cup-shaped morphology (electron microscopy), expressed exosome-marker proteins CD63, phosphatidylserine (flow cytometry) and TSG101 (immunoblotting), besides expressing CD34+ cell lineage marker protein, CD34. In vitro, CD34+ exosomes replicated the angiogenic activity of CD34+ cells by increasing endothelial cell viability, proliferation, and tube formation on Matrigel. In vivo, the CD34+ exosomes stimulated angiogenesis in Matrigel plug and corneal assays. Interestingly, exosomes from CD34+ cells but not from CD34+ cell–depleted mononuclear cells had angiogenic activity. Conclusions: Our data demonstrate that human CD34+ cells secrete exosomes that have independent angiogenic activity both in vitro and in vivo. CD34+ exosomes may represent a significant component of the paracrine effect of progenitor cell transplantation for therapeutic angiogenesis.
Fair scheduling with QoS support in ad hoc networks

The paper studies fair scheduling with quality of service (QoS) support in ad hoc networks. The goal is to satisfy the minimum bandwidth requirements of guaranteed flows and to provide a fair share of residual bandwidth among all flows. We propose a new cluster-based mechanism called two-tier slot allocation protocol (2TSAP), which improves system throughput and ensures per-cluster fairness while satisfying the requirements of guaranteed flows. With 2TSAP, the network is logically partitioned into clusters, each with a scheduler. The scheduler assigns time slots to mobiles in the affiliated clusters based on the first tier algorithm. The mobiles scheduled to send at the next time slot then in turn assign the time slot to flows determined by the second tier algorithm. We compare the performance of 2TSAP with Q EMLM-FQ, a virtual-time based fair scheduling mechanism with QoS support. The simulation results show that 2TSAP meets the minimum requirements of guaranteed flows, shares the residual bandwidth fairly among all flows, and improves overall system throughput.
A Full GMP Process to Select and Amplify Epitope-Specific T Lymphocytes for Adoptive Immunotherapy of Metastatic Melanoma

A number of trials of adoptive transfer of tumor-specific T lymphocytes have been performed in the last 20 years in metastatic melanoma, with increasingly encouraging results as the relevant melanoma antigens were identified and the purity/specificity of injected T cells improved. We have previously described a sorting method of epitope-specific T lymphocytes that uses magnetic beads coated with HLA/peptide complexes and we suggested that this method could be applied to a clinical setting. In the present work, we provide a detailed description of the whole GMP process of sorting and amplification of clinical grade T cells specific for the melanoma antigens Melan-A and MELOE-1. All the reagents used in this process including the sorting reagent were produced in GMP conditions and we document the optimization of the different steps of the process such as peptide stimulation, sorting, and amplification. The optimized procedure, validated in 3 blank runs in a clinical setting, allowed the production of at least 108 pure (>90%) Melan-A- and MELOE-1-specific T cells within 28 days starting with 100 mL of blood from metastatic melanoma patients. This GMP process is thus ready to be used in an upcoming phase I/II clinical trial on metastatic melanoma patients.
An in vitro study of enamel surface microhardness following argon laser irradiation and acidulated phosphate fluoride treatment.

PURPOSE The purpose of this in vitro study was to evaluate the effect of low-fluence argon laser (AL) irradiation and acidulated phosphate fluoride (APF) gel treatment on enamel microhardness. METHODS Twelve mandibular permanent molars were selected for this study. The teeth were sectioned generating 4 flat enamel surfaces per tooth. The flattened enamel tooth surfaces were randomly assigned to 1 of 4 treatment groups: (1) no treatment (control); (2) the enamel surface was exposed to a 4-minute, 1.23% APF gel treatment; (3) the enamel surface was exposed to AL irradiation of 11.5 J/cm2 (0.23 1-W, 5-mm beam size, 10 seconds); and (4) the enamel surface was exposed to the same AL irradiation followed by an APF gel treatment. Using a Buehler Micromet II Digital Microhardness Tester, Knoop hardness was determined using a 1,000-gram load and a dwell time of 12 seconds. Five hardness values were recorded for each enamel surface. Data were analyzed using ANOVA and Fisher's least significant difference post-hoc test. RESULTS Mean surface hardness values (+/-SD) were 298+/-37 Knoop hardness (HK) for the no treatment (control), 270+/-70 HK for the APF-only group, 316+/-5 HK for the AL-only group, and 317+/-25 HK for the AL-before-APF group. The AL-only and AL-before-APF groups had significantly higher (P<.05) surface hardness values vs the APF-only group. CONCLUSIONS Enamel surface microhardness is higher when exposed to low AL irradiation only or AL before APF vs a no treatment (control) enamel surface.
Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection. Protection by T cells is MHC- restricted and MHC-regulated; a model for MHC-disease associations

The in vivo importance of class I MHC regulation of the Tc response to a natural pathogenic agent of high virulence was studied on the basis of our previous demonstration of a major difference in the capacity to generate a Sendai virus-specific Tc response between C57BL/6 (B6, H-2b) mice and H-2Kb mutant B6.C-H-2bm1 (bm 1) mice. These two mouse strains differ from each other only in three amino acids in the crucial H-2Kb restriction element for this response. bm 1 mice, in contrast to B6 mice, are Tc nonresponders against this virus, but show Sendai-specific T cell proliferation, antibody production, and DTH reactions, as well as NK cell activity, equal to those of B6 mice. B6, Sendai Tc-deficient bm 1 and T cell-deficient B6 nu/nu mice differ from each other in susceptibility to lethal pneumonia induced by i.n. inoculation of virulent Sendai virus. The lethal dose (LD50) in B6 mice averaged 152 TCID50, in bm 1 mice, 14 TCID50 and in B6 nu/nu mice 0.5 TCID50. The importance of Tc was also shown by the complete protection of B6 nu/nu mice against infection with a lethal virus dose by i.v. injection of a Sendai virus-specific, IL-2-dependent and H-2Kb-restricted B6 Tc clone. In vivo protection by this Tc clone was H-2Kb-restricted. Apart from Tc, an important role for virus-specific Th cells is evident from the difference in susceptibility between bm 1 and B6 nu/nu mice. This conclusion was supported by the demonstration that the mean survival time of B6 nu/nu and bm 1 nu/nu mice could be significantly prolonged, in an I-Ab-restricted manner, by the injection of in vitro-propagated, Sendai-specific B6 or bm 1 Th clones after a lethal dose of Sendai virus, and by the demonstration that inoculation of these Th clones provided help to virus-specific Tc by means of IL-2 production. Strikingly, Th and Tc cooperate in anti-Sendai virus immunity, since permanent survival of lethally infected nu/nu mice was only achieved by inoculation of a mixture of Tc and Th clones or a mixture of a Tc clone and rIL-2. This study provides a unique model for the study of MHC- disease associations.
Advice on the safe introduction and continued use of isotretinoin in acne in the U.K. 2010

Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. *Department of Dermatology, Cumberland Infirmary, Carlisle CA2 7HY, U.K. Independent Acne Patient Advisor, Belfast City Hospital, Belfast BT9 7AB, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. §Department of Dermatology, The Park Hospital, Arnold, Nottingham NG5 5BX, U.K. –Department of Dermatology, Nuffield Health Newcastle upon Tyne Hospital, Newcastle upon Tyne NE2 1JP, U.K. **Department of Dermatology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZN, U.K.
An improved NLMS algorithm based on speech enhancement

Currently, adaptive noise cancellation algorithm is the mainstream technology in the field of noise cancellation, many research schemes are put forward on the basis of it. Least mean square (LMS) adaptive algorithm is the first one to be studied, there are many modified algorithm based on LMS, such as Normalized Least Mean Square (NLMS), Proportionate NLMS (PNLMS), etc. All kinds of adaptive algorithms have their own advantages and disadvantages, and their corresponding improvement schemes are different. With increasing requirement from adaptive noise cancellation in practical applications, these algorithms are constantly growing and improving. By studying the principles of adaptive noise cancellation (ANC), this article uses the regularization NLMS algorithm to improve its application in noise cancellation system and compares the simulation results of some performance with traditional NLMS algorithm. In speech signal processing, both methods can suppress interference signals to extract useful signals from the high background noise. However, the regularization NLMS algorithm can exhibit a faster convergence, a greater stability and a better ability to suppress interference.
Macrophage-mediated corpse engulfment is required for normal Drosophila CNS morphogenesis

Cell death plays an essential role in development, and the removal of cell corpses presents an important challenge for the developing organism. Macrophages are largely responsible for the clearance of cell corpses in Drosophila melanogaster and mammalian systems. We have examined the developmental requirement for macrophages in Drosophila and find that macrophage function is essential for central nervous system (CNS) morphogenesis. We generate and analyze mutations in the Pvr locus, which encodes a receptor tyrosine kinase of the PDGF/VEGF family that is required for hemocyte migration. We find that loss of Pvr function causes the mispositioning of glia within the CNS and the disruption of the CNS axon scaffold. We further find that inhibition of hemocyte development or of Croquemort, a receptor required for macrophage-mediated corpse engulfment, causes similar CNS defects. These data indicate that macrophage-mediated clearance of cell corpses is required for proper morphogenesis of the Drosophila CNS.
Elevated NF-κB Activation Is Conserved in Human Myocytes Cultured From Obese Type 2 Diabetic Patients and Attenuated by AMP-Activated Protein Kinase

OBJECTIVE To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes. RESEARCH DESIGN AND METHODS Muscle precursor cells were isolated from four age-matched subject groups: 1) nonobese, normal glucose tolerant; 2) obese, normal glucose tolerant; 3) obese, impaired glucose tolerant; and 4) obese, type 2 diabetes (T2D). The level of inflammation (nuclear factor-κB [NF-κB] signaling) and effect of pharmacological AMPK activation was assessed by Western blots, enzyme-linked immunosorbent assay, and radioactive assays (n = 5 for each subject group). RESULTS NF-κB-p65 DNA binding activity was significantly elevated in myocytes from obese T2D patients compared with nonobese control subjects. This correlated to a significant increase in tumor necrosis factor-α concentration in cell culture media. In addition, insulin-stimulated glucose uptake was completely suppressed in myocytes from obese impaired glucose tolerant and T2D subjects. It is interesting that activation of AMPK by A769662 attenuated NF-κB-p65 DNA binding activity in obese T2D cells to levels measured in nonobese myocytes; however, this had no effect on insulin sensitivity of the cells. CONCLUSIONS This work provides solid evidence that differentiated human muscle precursor cells maintain in vivo phenotypes of inflammation and insulin resistance and that obesity alone may not be sufficient to establish inflammation in these cells. It is important that we demonstrate an anti-inflammatory role for AMPK in these human cells. Despite attenuation of NF-κB activity by AMPK, insulin resistance in obese T2D cells remained, suggesting factors in addition to inflammation may contribute to the insulin resistance phenotype in muscle cells.
Accelerated and safe expansion of human mesenchymal stromal cells in animal serum‐free medium for transplantation and regenerative medicine

Human bone marrow mesenchymal stromal cells (hMSC) are currently investigated for a variety of therapeutic applications. However, most expansion protocols still use fetal calf serum (FCS) as growth factor supplement which is a potential source of undesired xenogeneic pathogens. We established an expansion protocol for hMSC based on the use of GMP‐produced basic medium LP02 supplemented with 5% of platelet lysate (PL) obtained from human thrombocyte concentrates. Compared to FCS‐supplemented culture conditions, we found a significant increase in both colony forming unit‐fibroblast (CFU‐F) as well as cumulative cell numbers after expansion. This accelerated growth is optimized by pooling of at least 10 thrombocyte concentrates. A minimal requirement is the use of 5% of PL with an optimal platelet concentration of 1.5 × 109/ml, and centrifugation of thawed lysate at high speed. Cells expanded by this protocol meet all criteria for mesenchymal stromal cells (MSCs), e.g. plastic adherence, spindle‐shaped morphology, surface marker expression, lack of hematopoietic markers, and differentiation capability into three mesenchymal lineages. MSC at passage 6 were cytogenetically normal and retained their immune‐privileged potential by suppressing allogeneic reaction of T‐cells. Additionally, gene expression profiles show increased mRNA levels of genes involved in cell cycle and DNA replication and downregulation of developmental and differentiation genes, supporting the observation of increased MSC‐expansion in PL‐supplemented medium. In summary, we have established a GMP‐compatible protocol for safe and accelerated expansion of hMSC to be used in cell and tissue therapy. J. Cell. Physiol. 213: 18–26, 2007. © 2007 Wiley‐Liss, Inc.
Toxicity Evaluation of Two Dental Composites: Three-Dimensional Confocal Laser Scanning Microscopy Time-Lapse Imaging of Cell Behavior

Abstract The purpose of this study was to investigate the in vitro biocompatibility of two dental composites (namely A and B) with similar chemical composition used for direct restoration using three-dimensional confocal laser scanning microscopy (CLSM) time-lapse imaging. Time-lapse imaging was performed on cultured human HGF-1 fibroblast-like cells after staining using Live/Dead®. Image analysis showed a higher mortality rate in the presence of composite A than composite B. The viability rate decreased in a time-dependent manner during the 5 h of exposure. Morphological alterations were associated with toxic effects; cells were enlarged and more rounded in the presence of composite A as shown by F-actin and cell nuclei staining. Resazurin assay was used to confirm the active potential of composites in cell metabolism; results showed severe cytotoxic effects in the presence of both no light-curing composites after 24 h of direct contact. However, extracts of polymerized composites induced a moderate decrease in cell metabolism after the same incubation period. Composite B was significantly better tolerated than composite A at all investigated end points and all time points. The finding confirmed that the used CLSM method was sufficiently sensitive to differentiate the biocompatibility behavior of two composites based on similar methacrylate monomers.
Influence of class size on physical activity behavior changes in a 15-week health-related fitness course

Objective - The purpose of this study was to determine if class size in a health-related fitness course affects physical activity behaviors of urban, commuter university students. Methods - Survey questions related to physical activity behaviors were administered to 653 students enrolled in small (~40 students) or large (~100 students) health-related fitness courses (small experimental, SE or large experimental, LE) designed to promote positive physical activity patterns or a control group (C). The data were analyzed using ANOVA and Chi-Square tests. Results - Following the 15-week intervention, patterns emerged suggesting that the SE was more effective than the LE in eliciting increases in the quantity and quality of physical activity. When the data were dichotomized to reflect compliance with minimal standards, the SE group had a significantly (p<.05) greater proportion of subjects compared to the LE group who reported exercising 150 + minutes/week (14.6% vs 5.3%, respectively) and who achieved 450 + MET . minutes/week of physical activity (17.3% vs 4.6%, respectively). For the subjects classified in the active stages of change (action and maintenance), only the LE group (7.4% change) reported a significant increase (p<.05) in the proportion who were active, though a trend for the SE group (9.6% change) to increase (p=.066) was observed. Regarding physical activity enjoyment, there were no differences found among groups. Conclusion Based on the findings from the present study, class size in a 15-week health-related fitness course appears to affect changes in physical activity behaviors. Therefore, if a primary goal of health-related fitness courses is to increase participation in physical activity, it would be a prudent policy to limit enrollment in such courses.
miR-124 Regulates Diverse Aspects of Rhythmic Behavior in Drosophila

Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions. Despite substantial knowledge of central clock machineries, we have less understanding of how the central clock's behavioral outputs are regulated. Here, we identify Drosophila miR-124 as a critical regulator of diurnal activity. During normal light/dark cycles, mir-124 mutants exhibit profoundly abnormal locomotor activity profiles, including loss of anticipatory capacities at morning and evening transitions. Moreover, mir-124 mutants exhibited striking behavioral alterations in constant darkness (DD), including a temporal advance in peak activity. Nevertheless, anatomical and functional tests demonstrate a normal circadian pacemaker in mir-124 mutants, indicating this miRNA regulates clock output. Among the extensive miR-124 target network, heterozygosity for targets in the BMP pathway substantially corrected the evening activity phase shift in DD. Thus, excess BMP signaling drives specific circadian behavioral output defects in mir-124 knock-outs. SIGNIFICANCE STATEMENT Circadian clocks control rhythmic behaviors of most life-forms. Despite extensive knowledge of the central clock, there is less understanding of how its behavioral outputs are regulated. Here, we identify a conserved neural microRNA as a critical regulator of diurnal behavior. We find Drosophila mir-124 mutants exhibit robust activity abnormalities during normal light/dark cycles and during constant darkness. Nevertheless, as the central pacemaker is functional in these mutants, miR-124 regulates clock output. We provide mechanistic insight by showing deregulation of miR-124 targets in BMP signaling drives specific mir-124 defects. In summary, Drosophila mir-124 mutants reveal post-transcriptional control of circadian activities, and impact of BMP signaling in behavioral output.
Selective Etching of Metallic Carbon Nanotubes by Gas-Phase Reaction

Metallic and semiconducting carbon nanotubes generally coexist in as-grown materials. We present a gas-phase plasma hydrocarbonation reaction to selectively etch and gasify metallic nanotubes, retaining the semiconducting nanotubes in near-pristine form. With this process, 100% of purely semiconducting nanotubes were obtained and connected in parallel for high-current transistors. The diameter- and metallicity-dependent “dry” chemical etching approach is scalable and compatible with existing semiconductor processing for future integrated circuits.
Optimal Hopping in Ad Hoc Wireless Networks

Gupta and Kumar showed that throughput in a static random wireless network increases with the amount of hopping. In a subsequent paper (2004), it was shown that although throughput benefits from a large number of hops, this comes at the expense of higher delay. Separately, several studies have shown that in ad hoc networks, transmission energy decreases as hopping increases. However, when transceiver circuit energy is also taken into account, hopping as much as possible no longer maximizes energy efficiency and the optimal amount of hopping depends on the topology and size of the network. This paper attempts to unify these earlier results by estab- lishing the optimal hopping for energy efficiency along with throughput and delay. A random network model with n nodes in area A(n) is considered. The effect of interference is captured by the Physical model and the signal is assumed to decay with distance r as r �δ ,δ> 1. Both transmission and transceiver circuit energy are taken into account. Optimal trade-offs between throughput, delay and energy-per-bit scaling for this random network model are established. These results show that the amount of hopping still determines the optimal trade-off and yield the amount of hopping that should be used to achieve any point of the optimal trade-off. In a constant area network, where A(n )=1 , Θ(1) hops result in the best energy and delay scaling
Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition

The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements. The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus, a process known as Adaptation, which is dependent on the Cas1 and Cas2 proteins. We demonstrate that Cas1 catalyses an efficient trans-esterification reaction on branched DNA substrates, which represents the reverse- or disintegration reaction. Cas1 from both Escherichia coli and Sulfolobus solfataricus display sequence specific activity, with a clear preference for the nucleotides flanking the integration site at the leader-repeat 1 boundary of the CRISPR locus. Cas2 is not required for this activity and does not influence the specificity. This suggests that the inherent sequence specificity of Cas1 is a major determinant of the adaptation process. DOI: http://dx.doi. org/10.7554/eLife.08716. 001