7 CFR 51.1837 - Classification of defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS) United States Standards for Grades of Florida Tangerines Definitions § 51.1837 Classification of...) at stem end, or the equivalent of this amount, by volume, when occurring in other portions of the fruit Affecting all segments more than 1/4 inch (6.4 mm) at stem end, or the equivalent of this amount...

7 CFR 51.1175 - Classification of defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS) United States Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1175... segments more than 1/4 inch (6.4 mm) at stem end, or the equivalent of this amount, by volume, when occurring in other portions of the fruit Affecting all segments more than 1/2 inch (12.7 mm) at stem end, or...

7 CFR 51.1175 - Classification of defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS) United States Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1175... segments more than 1/4 inch (6.4 mm) at stem end, or the equivalent of this amount, by volume, when occurring in other portions of the fruit Affecting all segments more than 1/2 inch (12.7 mm) at stem end, or...

Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip.

PubMed

Zhang, Jie; Wei, Xiaofeng; Zeng, Rui; Xu, Feng; Li, XiuJun

2017-06-01

Microfluidic lab-on-a-chip provides a new platform with unique advantages to mimic complex physiological microenvironments in vivo and has been increasingly exploited to stem cell research. In this review, we highlight recent advances of microfluidic devices for stem cell culture and differentiation toward the development of organ-on-a-chip, especially with an emphasis on vital innovations within the last 2 years. Various aspects for improving on-chip stem-cell culture and differentiation, particularly toward organ-on-a-chip, are discussed, along with microenvironment control, surface modification, extracellular scaffolds, high throughput and stimuli. The combination of microfluidic technologies and stem cells hold great potential toward versatile systems of 'organ-on-a-chip' as desired. Adapted with permission from [1-8].

7 CFR 51.1565 - Internal defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5 percent waste 10 percent waste... Occurring entirely within the vascular ring Internal Brown Spot and Similar Discoloration (Heat Necrosis...

7 CFR 51.1565 - Internal defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5 percent waste 10 percent waste... Occurring entirely within the vascular ring Internal Brown Spot and Similar Discoloration (Heat Necrosis...

Physical-level synthesis for digital lab-on-a-chip considering variation, contamination, and defect.

PubMed

Liao, Chen; Hu, Shiyan

2014-03-01

Microfluidic lab-on-a-chips have been widely utilized in biochemical analysis and human health studies due to high detection accuracy, high timing efficiency, and low cost. The increasing design complexity of lab-on-a-chips necessitates the computer-aided design (CAD) methodology in contrast to the classical manual design methodology. A key part in lab-on-a-chip CAD is physical-level synthesis. It includes the lab-on-a-chip placement and routing, where placement is to determine the physical location and the starting time of each operation and routing is to transport each droplet from the source to the destination. In the lab-on-a-chip design, variation, contamination, and defect need to be considered. This work designs a physical-level synthesis flow which simultaneously considers variation, contamination, and defect of the lab-on-a-chip design. It proposes a maze routing based, variation, contamination, and defect aware droplet routing technique, which is seamlessly integrated into an existing placement technique. The proposed technique improves the placement solution for routing and achieves the placement and routing co-optimization to handle variation, contamination, and defect. The simulation results demonstrate that our technique does not use any defective/contaminated grids, while the technique without considering contamination and defect uses 17.0% of the defective/contaminated grids on average. In addition, our routing variation aware technique significantly improves the average routing yield by 51.2% with only 3.5% increase in completion time compared to a routing variation unaware technique.

In vivo bone regeneration with injectable chitosan/hydroxyapatite/collagen composites and mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Huang, Zhi; Chen, Yan; Feng, Qing-Ling; Zhao, Wei; Yu, Bo; Tian, Jing; Li, Song-Jian; Lin, Bo-Miao

2011-09-01

For reconstruction of irregular bone defects, injectable biomaterials are more appropriate than the preformed biomaterials. We herein develop a biomimetic in situ-forming composite consisting of chitosan (CS) and mineralized collagen fibrils (nHAC), which has a complex hierarchical structure similar to natural bone. The CS/nHAC composites with or without mesenchymal stem cells (MSCs) are injected into cancellous bone defects at the distal end of rabbit femurs. Defects are assessed by radiographic, histological diagnosis and Raman microscopy until 12 weeks. The results show that MSCs improve the biocompatibility of CS/nHAC composites and enhance new bone formation in vivo at 12 weeks. It can be concluded that the injectable CS/nHAC composites combined with MSCs may be a novel method for reconstruction of irregular bone defects.

7 CFR 51.1565 - Internal defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5... Discoloration (Heat Necrosis) Not more than the equivalent of 3 scattered spots 1/8 inch in diameter in a potato...

7 CFR 51.1565 - Internal defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5... Discoloration (Heat Necrosis) Not more than the equivalent of 3 scattered spots 1/8 inch in diameter in a potato...

Detection of solder bump defects on a flip chip using vibration analysis

NASA Astrophysics Data System (ADS)

Liu, Junchao; Shi, Tielin; Xia, Qi; Liao, Guanglan

2012-03-01

Flip chips are widely used in microelectronics packaging owing to the high demand of integration in IC fabrication. Solder bump defects on flip chips are difficult to detect, because the solder bumps are obscured by the chip and substrate. In this paper a nondestructive detection method combining ultrasonic excitation with vibration analysis is presented for detecting missing solder bumps, which is a typical defect in flip chip packaging. The flip chip analytical model is revised by considering the influence of spring mass on mechanical energy of the system. This revised model is then applied to estimate the flip chip resonance frequencies. We use an integrated signal generator and power amplifier together with an air-coupled ultrasonic transducer to excite the flip chips. The vibrations are measured by a laser scanning vibrometer to detect the resonance frequencies. A sensitivity coefficient is proposed to select the sensitive resonance frequency order for defect detection. Finite element simulation is also implemented for further investigation. The results of analytical computation, experiment, and simulation prove the efficacy of the revised flip chip analytical model and verify the effectiveness of this detection method. Therefore, it may provide a guide for the improvement and innovation of the flip chip on-line inspection systems.

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely... discoloration (Heat Necrosis) Not more than the equivalent of 3 scattered spots 1/8 inch in diameter in a potato...

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely... discoloration (Heat Necrosis) Not more than the equivalent of 3 scattered spots 1/8 inch in diameter in a potato...

Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in nonquiescent hematopoietic stem and progenitor cells.

PubMed

Desai, Amar; Qing, Yulan; Gerson, Stanton L

2014-02-01

Hematopoietic stem cell (HSC) populations require DNA repair pathways to maintain their long-term survival and reconstitution capabilities, but mediators of these processes are still being elucidated. Exonuclease 1 (Exo1) participates in homologous recombination (HR) and Exo1 loss results in impaired 5' HR end resection. We use cultured Exo1(mut) fibroblasts and bone marrow to demonstrate that loss of Exo1 function results in defective HR in cycling cells. Conversely, in Exo1(mut) mice HR is not required for maintenance of quiescent HSCs at steady state, confirming the steady state HSC reliance on nonhomologous end joining (NHEJ). Exo1(mut) mice sustained serial repopulation, displayed no defect in competitive repopulation or niche occupancy, and exhibited no increased sensitivity to whole body ionizing radiation. However, when Exo1(mut) HSCs were pushed into cell cycle in vivo with 5-fluorouracil or poly IC, the hematopoietic population became hypersensitive to IR, resulting in HSC defects and animal death. We propose Exo1-mediated HR is dispensable for stem cell function in quiescent HSC, whereas it is essential to HSC response to DNA damage processing after cell cycle entry, and its loss is not compensated by intact NHEJ. In HSCs, the maintenance of stem cell function after DNA damage is dependent on the DNA repair capacity, segregated by active versus quiescent points in cell cycle. © AlphaMed Press.

Automated Inspection of Defects in Optical Fiber Connector End Face Using Novel Morphology Approaches.

PubMed

Mei, Shuang; Wang, Yudan; Wen, Guojun; Hu, Yang

2018-05-03

Increasing deployment of optical fiber networks and the need for reliable high bandwidth make the task of inspecting optical fiber connector end faces a crucial process that must not be neglected. Traditional end face inspections are usually performed by manual visual methods, which are low in efficiency and poor in precision for long-term industrial applications. More seriously, the inspection results cannot be quantified for subsequent analysis. Aiming at the characteristics of typical defects in the inspection process for optical fiber end faces, we propose a novel method, “difference of min-max ranking filtering” (DO2MR), for detection of region-based defects, e.g., dirt, oil, contamination, pits, and chips, and a special model, a “linear enhancement inspector” (LEI), for the detection of scratches. The DO2MR is a morphology method that intends to determine whether a pixel belongs to a defective region by comparing the difference of gray values of pixels in the neighborhood around the pixel. The LEI is also a morphology method that is designed to search for scratches at different orientations with a special linear detector. These two approaches can be easily integrated into optical inspection equipment for automatic quality verification. As far as we know, this is the first time that complete defect detection methods for optical fiber end faces are available in the literature. Experimental results demonstrate that the proposed DO2MR and LEI models yield good comprehensive performance with high precision and accepted recall rates, and the image-level detection accuracies reach 96.0 and 89.3%, respectively.

Implantation of Autologous Cartilage Chips Improves Cartilage Repair Tissue Quality in Osteochondral Defects: A Study in Göttingen Minipigs.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke; Hede, Kris Chadwick; Lind, Martin

2016-06-01

Osteochondral injuries have poor endogenous healing potential, and no standard treatment has been established. The use of combined layered autologous bone and cartilage chips for treatment of osteochondral defects has shown promising short-term clinical results. This study aimed to investigate the role of cartilage chips by comparing combined layered autologous bone and cartilage chips with autologous bone implantation alone in a Göttingen minipig model. The hypothesis was that the presence of cartilage chips would improve the quality of the repair tissue. Controlled laboratory study. Twelve Göttingen minipigs received 2 osteochondral defects in each knee. The defects were randomized to autologous bone graft (ABG) combined with autologous cartilage chips (autologous dual-tissue transplantation [ADTT]) or ABG alone. Six animals were euthanized at 6 months and 6 animals were euthanized at 12 months. Follow-up evaluation consisted of histomorphometry, immunohistochemistry, semiquantitative scoring (International Cartilage Repair Society II), and computed tomography. There was significantly more hyaline cartilage in the ADTT group (25.8%) compared with the ABG group (12.8%) at 6 months after treatment. At 12 months, the fraction of hyaline cartilage in the ABG group had significantly decreased to 4.8%, whereas the fraction of hyaline cartilage in the ADTT group was unchanged (20.1%). At 6 and 12 months, there was significantly more fibrocartilage in the ADTT group (44% and 60.8%) compared with the ABG group (24.5% and 41%). The fraction of fibrous tissue was significantly lower in the ADTT group compared with the ABG group at both 6 and 12 months. The implanted cartilage chips stained >75% positive for collagen type 4 and laminin at both 6 and 12 months. Significant differences were found in a number of International Cartilage Repair Society II subcategories. The volume of the remaining bone defect significantly decreased from 6 to 12 months in both treatment groups; however, no difference in volume was found between the groups at either 6 or 12 months. The presence of cartilage chips in an osteochondral defect facilitated the formation of fibrocartilage as opposed to fibrous tissue at both 6 and 12 months posttreatment. The implanted chips were present in the defect and viable after 12 months. This study substantiates the chondrogenic role of cartilage chips in osteochondral defects. © 2016 The Author(s).

Implantation of Allogenic Synovial Stem Cells Promotes Meniscal Regeneration in a Rabbit Meniscal Defect Model

PubMed Central

Horie, Masafumi; Driscoll, Matthew D.; Sampson, H. Wayne; Sekiya, Ichiro; Caroom, Cyrus T.; Prockop, Darwin J.; Thomas, Darryl B.

2012-01-01

Update This article was updated on May 16, 2012, because of a previous error. The legend for Figures 7-A and 7-B that had previously read “Representative macroscopic appearance (Fig. 7-A) and histological sections (Fig. 7-B) of the meniscal defect one day to twelve weeks after the implantation of GFP-positive green fluorescent protein under fluorescence” now reads “Representative macroscopic appearance (Fig. 7-A) and histological sections (Fig. 7-B) of the meniscal defect one day to twelve weeks after the implantation of GFP-positive synovial mesenchymal stem cells under fluorescence.” Background: Indications for surgical meniscal repair are limited, and failure rates remain high. Thus, new ways to augment repair and stimulate meniscal regeneration are needed. Mesenchymal stem cells are multipotent cells present in mature individuals and accessible from peripheral connective tissue sites, including synovium. The purpose of this study was to quantitatively evaluate the effect of implantation of synovial tissue-derived mesenchymal stem cells on meniscal regeneration in a rabbit model of partial meniscectomy. Methods: Synovial mesenchymal stem cells were harvested from the knee of one New Zealand White rabbit, expanded in culture, and labeled with a fluorescent marker. A reproducible 1.5-mm cylindrical defect was created in the avascular portion of the anterior horn of the medial meniscus bilaterally in fifteen additional rabbits. Allogenic synovial mesenchymal stem cells suspended in phosphate-buffered saline solution were implanted into the right knees, and phosphate-buffered saline solution alone was placed in the left knees. Meniscal regeneration was evaluated histologically at four, twelve, and twenty-four weeks for (1) quantity and (2) quality (with use of an established three-component scoring system). A similar procedure was performed in four additional rabbits with use of green fluorescent protein-positive synovial mesenchymal stem cells for the purpose of tracking progeny following implantation. Results: The quantity of regenerated tissue in the group that had implantation of synovial mesenchymal stem cells was greater at all end points, reaching significance at four and twelve weeks (p < 0.05). Tissue quality scores were also superior in knees treated with mesenchymal stem cells compared with controls at all end points, achieving significance at twelve and twenty-four weeks (3.8 versus 2.8 at four weeks [p = 0.29], 5.7 versus 1.7 at twelve weeks [p = 0.008], and 6.0 versus 3.9 at twenty-four weeks [p = 0.021]). Implanted cells adhered to meniscal defects and were observed in the regenerated tissue, where they differentiated into type-I and II collagen-expressing cells, at up to twenty-four weeks. Conclusions: Synovial mesenchymal stem cells adhere to sites of meniscal injury, differentiate into cells resembling meniscal fibrochondrocytes, and enhance both quality and quantity of meniscal regeneration. Clinical Relevance: These results may stimulate further exploration into the utility of synovial mesenchymal stem cells in the treatment of meniscal injury in large animals and humans. PMID:22517386

7 CFR 51.1565 - Internal defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Occurring entirely within the vascular ring Internal Brown Spot and Similar Discoloration (Heat Necrosis... or not entirely confined to the vascular ring Ingrown Sprouts, Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5 percent waste 10 percent waste...

Functional differentiation of human pluripotent stem cells on a chip.

PubMed

Giobbe, Giovanni G; Michielin, Federica; Luni, Camilla; Giulitti, Stefano; Martewicz, Sebastian; Dupont, Sirio; Floreani, Annarosa; Elvassore, Nicola

2015-07-01

Microengineering human "organs-on-chips" remains an open challenge. Here, we describe a robust microfluidics-based approach for the differentiation of human pluripotent stem cells directly on a chip. Extrinsic signal modulation, achieved through optimal frequency of medium delivery, can be used as a parameter for improved germ layer specification and cell differentiation. Human cardiomyocytes and hepatocytes derived on chips showed functional phenotypes and responses to temporally defined drug treatments.

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

PubMed Central

Varela, Christine; Denis, Jérôme Alexandre; Polentes, Jérôme; Feyeux, Maxime; Aubert, Sophie; Champon, Benoite; Piétu, Geneviève; Peschanski, Marc; Lefort, Nathalie

2012-01-01

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines. PMID:22269325

Drosophila CHIP protects against mitochondrial dysfunction by acting downstream of Pink1 in parallel with Parkin.

PubMed

Chen, Jia; Xue, Jin; Ruan, Jingsong; Zhao, Juan; Tang, Beisha; Duan, Ranhui

2017-12-01

Mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin function in a common pathway to regulate mitochondrial homeostasis contributing to the pathogenesis of Parkinson disease. The carboxyl terminus of Hsc70-interacting protein (CHIP) acts as a heat shock protein 70/heat shock protein 90 cochaperone to mediate protein folding or as an E3 ubiquitin ligase to target proteins for degradation. In this study, overexpression of Drosophila CHIP suppressed a range of Pink1 mutant phenotypes in flies, including abnormal wing posture, thoracic indentation, locomotion defects, muscle degeneration, and loss of dopaminergic neurons. Mitochondrial defects of Pink1 mutant, such as excessive fusion, reduced ATP content, and crista disorganization, were rescued by CHIP but not its ligase-dead mutants. Similar phenotypes and mitochondrial impairment were ameliorated in Parkin mutant flies by wild-type CHIP. Inactivation of CHIP with null fly mutants resulted in mitochondrial defects, such as reduced thoracic ATP content at 3 d old, decreased thoracic mitochondrial DNA content, and defective mitochondrial morphology at 60 d old. CHIP mutants did not exacerbate the phenotypes of Pink1 mutant flies but markedly shortened the life span of Parkin mutant flies. These results indicate that CHIP is involved in mitochondrial integrity and may act downstream of Pink1 in parallel with Parkin.-Chen, J., Xue, J., Ruan, J., Zhao, J., Tang, B., Duan, R. Drosophila CHIP protects against mitochondrial dysfunction by acting downstream of Pink1 in parallel with Parkin. © FASEB.

A novel bone scraper for intraoral harvesting: a device for filling small bone defects.

PubMed

Zaffe, Davide; D'Avenia, Ferdinando

2007-08-01

To evaluate histologically the morphology and characteristics of bone chips harvested intraorally by Safescraper, a specially designed cortical bone collector. Bone chips harvested near a bone defect or in other intraoral sites were grafted into a post-extractive socket or applied in procedures for maxillary sinus floor augmentation or guided bone regeneration. Core biopsies were performed at implant insertion. Undecalcified specimens embedded in PMMA were studied by histology, histochemistry and SEM. Intraoral harvesting by Safescraper provided a simple, clinically effective regenerative procedure with low morbidity for collecting cortical bone chips (0.9-1.7 mm in length, roughly 100 microm thick). Chips had an oblong or quadrangular shape and contained live osteocytes (mean viability: 45-72%). Bone chip grafting produced newly formed bone tissue suitable for implant insertion. Trabecular bone volume measured on biopsies decreased with time (from 45-55% to 23%). Grafted chips made up 50% or less of the calcified tissue in biopsies. Biopsies presented remodeling activities, new bone formation by apposition and live osteocytes (35% or higher). In conclusion, Safescraper is capable of collecting adequate amounts of cortical bone chips from different intraoral sites. The procedure is effective for treating alveolar defects for endosseous implant insertion and provides good healing of small bone defects after grafting with bone chips. The study indicates that Safescraper is a very useful device for in-office bone harvesting procedures in routine peri-implant bone regeneration.

Failure Analysis Study and Long-Term Reliability of Optical Assemblies with End-Face Damage

NASA Technical Reports Server (NTRS)

Kichak, Robert A.; Ott, Melanie N.; Leidecker, Henning W.; Chuska, Richard F.; Greenwell, Christopher J.

2008-01-01

In June 2005, the NESC received a multi-faceted request to determine the long term reliability of fiber optic termini on the ISS that exhibited flaws not manufactured to best workmanship practices. There was a lack of data related to fiber optic workmanship as it affects the long term reliability of optical fiber assemblies in a harsh environment. A fiber optic defect analysis was requested which would find and/or create various types of chips, spalls, scratches, etc., that were identified by the ISS personnel. Once the defects and causes were identified the next step would be to perform long term reliability testing of similar assemblies with similar defects. The goal of the defect analysis would be for the defects to be observed and documented for deterioration of fiber optic performance. Though this report mostly discusses what has been determined as evidence of poor manufacturing processes, it also concludes the majority of the damage could have been avoided with a rigorous process in place.

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ring Internal Black Spot, Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely within the vascular ring Hollow Heart or... diameter in a 10 ounce potato. 1 Internal Brown Spot and similar discoloration (Heat Necrosis) Not more...

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... ring Internal Black Spot, Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely within the vascular ring Hollow Heart or... diameter in a 10 ounce potato. 1 Internal Brown Spot and similar discoloration (Heat Necrosis) Not more...

7 CFR 51.3416 - Classification of defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Maximum allowed for U.S. No. 2 processing Occurring outside of or not entirely confined to the vascular ring Internal Black Spot, Internal Discoloration, Vascular Browning, Fusarium Wilt, Net Necrosis, Other Necrosis, Stem End Browning 5% waste 10% waste. Occurring entirely within the vascular ring Hollow Heart or...

Polydimethylsiloxane SlipChip for mammalian cell culture applications.

PubMed

Chang, Chia-Wen; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

2015-11-07

This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications.

Localization of burn mark under an abnormal topography on MOSFET chip surface using liquid crystal and emission microscopy tools.

PubMed

Lau, C K; Sim, K S; Tso, C P

2011-01-01

This article focuses on the localization of burn mark in MOSFET and the scanning electron microscope (SEM) inspection on the defect location. When a suspect abnormal topography is shown on the die surface, further methods to pin-point the defect location is necessary. Fault localization analysis becomes important because an abnormal spot on the chip surface may and may not have a defect underneath it. The chip surface topography can change due to the catastrophic damage occurred at layers under the chip surface, but it could also be due to inconsistency during metal deposition in the wafer fabrication process. Two localization techniques, liquid crystal thermography and emission microscopy, were performed to confirm that the abnormal topography spot is the actual defect location. The tiny burn mark was surfaced by performing a surface decoration at the defect location using hot hydrochloric acid. SEM imaging, which has the high magnification and three-dimensional capabilities, was used to capture the images of the burn mark. Copyright © 2011 Wiley Periodicals, Inc.

Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.

PubMed

Xiao, Meng; Yan, Ming; Zhang, Jianjun; Xu, Qin; Qi, Shengcai; Wang, Xu; Chen, Wantao

2017-04-01

Our previous studies have identified that CD166 works as a cancer stem-like cell (CSC) marker in epithelial cancers with a large repertoire of cellular functions. However, the post-translational regulatory mechanisms underlying CD166 turnover remain elusive. Several independent studies have reported that E3 ubiquitin ligase CHIP revealed significant biological effects through ubiquitin proteasome pathway on some kinds of malignant tumors. With analyzing the effects of CHIP expressions on stem-like cell populations, we found that CHIP represses CSC characteristics mainly targeting the CSC related protein CD166 in head and neck cancer (HNC). To investigate the role and relationship between CD166 and CHIP, HNC tissues and cell lines were used in this study. A significant negative correlation was observed between the expression levels of CHIP and CD166 in HNC patient samples. We also found that CHIP directly regulates the stability of CD166 protein through the ubiquitin proteasome system, which was also identified participating in the regulation of CSC behaviors in HNCs. Our findings demonstrate that CHIP-CD166-proteasome axis participates in regulating CSC properties in HNCs, suggesting that the regulation of CD166 by CHIP could provide new options for diagnosing and treating in the patients with HNCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chip-scale thermal management of high-brightness LED packages

NASA Astrophysics Data System (ADS)

Arik, Mehmet; Weaver, Stanton

2004-10-01

The efficiency and reliability of the solid-state lighting devices strongly depend on successful thermal management. Light emitting diodes, LEDs, are a strong candidate for the next generation, general illumination applications. LEDs are making great strides in terms of lumen performance and reliability, however the barrier to widespread use in general illumination still remains the cost or $/Lumen. LED packaging designers are pushing the LED performance to its limits. This is resulting in increased drive currents, and thus the need for lower thermal resistance packaging designs. As the power density continues to rise, the integrity of the package electrical and thermal interconnect becomes extremely important. Experimental results with high brightness LED packages show that chip attachment defects can cause significant thermal gradients across the LED chips leading to premature failures. A numerical study was also carried out with parametric models to understand the chip active layer temperature profile variation due to the bump defects. Finite element techniques were utilized to evaluate the effects of localized hot spots at the chip active layer. The importance of "zero defects" in one of the more popular interconnect schemes; the "epi down" soldered flip chip configuration is investigated and demonstrated.

Apparatus and method for the horizontal, crucible-free growth of silicon sheet crystals

DOEpatents

Ciszek, Theodore F.

1987-01-01

Apparatus for continuously forming a silicon crystal sheet from a silicon rod in a noncrucible environment. The rod is rotated and fed toward an RF coil in an inert atmosphere so that the upper end of the rod becomes molten and the silicon sheet crystal is pulled therefrom substantially horizontally in a continuous strip. A shorting ring may be provided around the rod to limit the heating to the upper end only. Argon gas can be used to create the inert atmosphere within a suitable closed chamber. By use of this apparatus and method, a substantially defect-free silicon crystal sheet is formed that can be used for microcircuitry chips or solar cells.

Controlling Differentiation of Stem Cells for Developing Personalized Organ-on-Chip Platforms.

PubMed

Geraili, Armin; Jafari, Parya; Hassani, Mohsen Sheikh; Araghi, Behnaz Heidary; Mohammadi, Mohammad Hossein; Ghafari, Amir Mohammad; Tamrin, Sara Hasanpour; Modarres, Hassan Pezeshgi; Kolahchi, Ahmad Rezaei; Ahadian, Samad; Sanati-Nezhad, Amir

2018-01-01

Organ-on-chip (OOC) platforms have attracted attentions of pharmaceutical companies as powerful tools for screening of existing drugs and development of new drug candidates. OOCs have primarily used human cell lines or primary cells to develop biomimetic tissue models. However, the ability of human stem cells in unlimited self-renewal and differentiation into multiple lineages has made them attractive for OOCs. The microfluidic technology has enabled precise control of stem cell differentiation using soluble factors, biophysical cues, and electromagnetic signals. This study discusses different tissue- and organ-on-chip platforms (i.e., skin, brain, blood-brain barrier, bone marrow, heart, liver, lung, tumor, and vascular), with an emphasis on the critical role of stem cells in the synthesis of complex tissues. This study further recaps the design, fabrication, high-throughput performance, and improved functionality of stem-cell-based OOCs, technical challenges, obstacles against implementing their potential applications, and future perspectives related to different experimental platforms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Defect Inspection of Flip Chip Solder Bumps Using an Ultrasonic Transducer

PubMed Central

Su, Lei; Shi, Tielin; Xu, Zhensong; Lu, Xiangning; Liao, Guanglan

2013-01-01

Surface mount technology has spurred a rapid decrease in the size of electronic packages, where solder bump inspection of surface mount packages is crucial in the electronics manufacturing industry. In this study we demonstrate the feasibility of using a 230 MHz ultrasonic transducer for nondestructive flip chip testing. The reflected time domain signal was captured when the transducer scanning the flip chip, and the image of the flip chip was generated by scanning acoustic microscopy. Normalized cross-correlation was used to locate the center of solder bumps for segmenting the flip chip image. Then five features were extracted from the signals and images. The support vector machine was adopted to process the five features for classification and recognition. The results show the feasibility of this approach with high recognition rate, proving that defect inspection of flip chip solder bumps using the ultrasonic transducer has high potential in microelectronics packaging.

NANOG priming before full reprogramming may generate germ cell tumours.

PubMed

Grad, I; Hibaoui, Y; Jaconi, M; Chicha, L; Bergström-Tengzelius, R; Sailani, M R; Pelte, M F; Dahoun, S; Mitsiadis, T A; Töhönen, V; Bouillaguet, S; Antonarakis, S E; Kere, J; Zucchelli, M; Hovatta, O; Feki, A

2011-11-09

Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

Dental and periodontal complications of lip and tongue piercing: prevalence and influencing factors.

PubMed

Plessas, A; Pepelassi, E

2012-03-01

The aim of this study was to compare the prevalence of lip and tongue piercing complications and explore the effect of ornament time wear period, habits, ornament morphology and periodontal biotype on the development of complications. One hundred and ten subjects with 110 lip and 51 tongue piercings were assessed for abnormal toothwear and/or tooth chipping/cracking (dental defects), gingival recession, clinical attachment loss and probing depth of teeth adjacent to the pierced site. Piercing habits (biting, rolling, stroking, sucking) were recorded. Wear time and habits significantly affected the prevalence of dental defects and gingival recession. Pierced site significantly affected dental defects prevalence, with greater prevalence for tongue than lip piercing. Wear time significantly affected attachment loss and probing depth. Attachment loss and probing depth did not significantly differ between tongue and lip piercings. Gingival recession was significantly associated with ornament height closure and stem length of tongue ornaments. Periodontal biotype was not significantly associated with gingival recession, attachment loss and probing depth. Dental defects prevalence is greater for tongue than lip piercing. Gingival recession is similar for tongue and lip piercing. Longer wear time of tongue and lip piercing is associated with greater prevalence of dental defects and gingival recession, as well as greater attachment loss and probing depth of teeth adjacent to pierced sites. Ornament morphology affects gingival recession prevalence. © 2012 Australian Dental Association.

Enhanced tenogenic differentiation and tendon-like tissue formation by CHIP overexpression in tendon-derived stem cells.

PubMed

Han, Weifeng; Chen, Lei; Liu, Junpeng; Guo, Ai

2017-04-01

The carboxyl terminus of Hsc70-interacting protein (CHIP, also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells. The potential function of CHIP in tendon-derived stem cells (TDSCs) remains largely unknown at present. Here, we investigated the effects of CHIP on tenogenic differentiation of TDSCs via lentivirus-mediated overexpression. Forced expression of CHIP induced morphological changes and significantly enhanced cell proliferation, as well as tendon differentiation in vitro. Upon stimulation with differentiation induction medium, CHIP-overexpressing TDSCs displayed significant inhibition of differentiation into osteogenic and adipogenic lineages. Subsequent implantation of TDSCs overexpressing CHIP with collagen sponges into nude mice induced a marked increase in ectopic tendon formation in vivo, compared with the control group. Our findings collectively suggest that CHIP is an important contributory factor to tenogenic tissue formation. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Detection of Hawthorn Fruit Defects Using Hyperspectral Imaging].

PubMed

Liu, De-hua; Zhang, Shu-juan; Wang, Bin; Yu, Ke-qiang; Zhao, Yan-ru; He, Yong

2015-11-01

Hyperspectral imaging technology covered the range of 380-1000 nm was employed to detect defects (bruise and insect damage) of hawthorn fruit. A total of 134 samples were collected, which included damage fruit of 46, pest fruit of 30, injure and pest fruit of 10 and intact fruit of 48. Because calyx · s⁻¹ tem-end and bruise/insect damage regions offered a similar appearance characteristic in RGB images, which could produce easily confusion between them. Hence, five types of defects including bruise, insect damage, sound, calyx, and stem-end were collected from 230 hawthorn fruits. After acquiring hyperspectral images of hawthorn fruits, the spectral data were extracted from region of interest (ROI). Then, several pretreatment methods of standard normalized variate (SNV), savitzky golay (SG), median filter (MF) and multiplicative scatter correction (MSC) were used and partial least squares method(PLS) model was carried out to obtain the better performance. Accordingly to their results, SNV pretreatment methods assessed by PLS was viewed as best pretreatment method. Lastly, SNV was chosen as the pretreatment method. Spectral features of five different regions were combined with Regression coefficients(RCs) of partial least squares-discriminant analysis (PLS-DA) model was used to identify the important wavelengths and ten wavebands at 483, 563, 645, 671, 686, 722, 777, 819, 837 and 942 nm were selected from all of the wavebands. Using Kennard-Stone algorithm, all kinds of samples were randomly divided into training set (173) and test set (57) according to the proportion of 3:1. And then, least squares-support vector machine (LS-SVM) discriminate model was established by using the selected wavebands. The results showed that the discriminate accuracy of the method was 91.23%. In the other hand, images at ten important wavebands were executed to Principal component analysis (PCA). Using "Sobel" operator and region growing algrorithm "Regiongrow", the edge and defect feature of 86 Hawthorn could be recognized. Lastly, the detect precision of bruised, insect damage and two-defect samples is 95.65%, 86.67% and 100%, respectively. This investigation demonstrated that hyperspectral imaging technology could detect the defects of bruise, insect damage, calyx, and stem-end in hawthorn fruit in qualitative analysis and feature detection which provided a theoretical reference for the defects nondestructive detection of hawthorn fruit.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

PubMed

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-04-20

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

PubMed Central

Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

2016-01-01

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft. PMID:27104525

Apparatus and method for the horizontal, crucible-free growth of silicon sheet crystals

DOEpatents

Ciszek, T.F.

1984-09-12

Apparatus is provided for continuously forming a silicon crystal sheet from a silicon rod in a non-crucible environment. The rod is rotated and fed toward an RF coil in an inert atmosphere so that the upper end of the rod becomes molten and the silicon sheet crystal is pulled therefrom substantially horizontally in a continuous strip. A shorting ring may be provided around the rod to limit the heating to the upper end only. Argon gas can be used to create the inert atmosphere within a suitable closed chamber. By use of this apparatus and method, a substantially defect-free silicon crystal sheet is formed which can be used for micro-circuitry chips or solar cells.

Impaction grafted bone chip size effect on initial stability in an acetabular model: Mechanical evaluation.

PubMed

Holton, Colin; Bobak, Peter; Wilcox, Ruth; Jin, Zhongmin

2013-01-01

Acetabular bone defect reconstruction is an increasing problem for surgeons with patients undergoing complex primary or revision total hip replacement surgery. Impaction bone grafting is one technique that has favourable long-term clinical outcome results for patients who undergo this reconstruction method for acetabular bone defects. Creating initial mechanical stability of the impaction bone graft in this technique is known to be the key factor in achieving a favourable implant survival rate. Different sizes of bone chips were used in this technique to investigate if the size of bone chips used affected initial mechanical stability of a reconstructed acetabulum. Twenty acetabular models were created in total. Five control models were created with a cemented cup in a normal acetabulum. Then five models in three different groups of bone chip size were constructed. The three groups had an acetabular protrusion defect reconstructed using either; 2-4 mm(3), 10 mm(3) or 20 mm(3) bone chip size for impaction grafting reconstruction. The models underwent compression loading up to 9500 N and displacement within the acetabular model was measured indicating the initial mechanical stability. This study reveals that, although not statistically significant, the largest (20 mm(3)) bone chip size grafted models have an inferior maximum stiffness compared to the medium (10 mm(3)) bone chip size. Our study suggests that 10 mm(3) size of bone chips provide better initial mechanical stability compared to smaller or larger bone chips. We dismissed the previously held opinion that the biggest practically possible graft is best for acetabular bone graft impaction.

Microchip problems plague DOD

NASA Astrophysics Data System (ADS)

Smith, R. J.

1984-10-01

The major issues in the controversy over the discovery of millions of defective microchips sold to the DOD by the Texas Instruments (TI) corporation are outlined. Defects in the microcircuits are blamed on inadequate testing procedures performed by TI during manufacture, and on inadequate testing procedures used by a subcontractor especially contracted to test the chips. Because the problem persisted over a period of years, defects might be possible in as many as 100 million chips used in a broad range of military applications including the Trident submarine, the B-52, B-1B, F-15, F-111, F-4, A-6, and A-7 aircraft, the Harpoon and HARM missile systems, and the Space Shuttles Discovery and Challenger. It is pointed out that although TI has accepted responsibility for the defective chips, little will be done by the DOD to compel the company to replace them, or to upgrade testing procedures. It is concluded that the serious nature of the problem could renew interest in recommendations for the standardization of military microcircuits.

Vortex nozzle for segmenting and transporting metal chips from turning operations

DOEpatents

Bieg, L.F.

1993-04-20

Apparatus for collecting, segmenting and conveying metal chips from machining operations utilizes a compressed gas driven vortex nozzle for receiving the chip and twisting it to cause the chip to segment through the application of torsional forces to the chip. The vortex nozzle is open ended and generally tubular in shape with a converging inlet end, a constant diameter throat section and a diverging exhaust end. Compressed gas is discharged through angled vortex ports in the nozzle throat section to create vortex flow in the nozzle and through an annular inlet at the entrance to the converging inlet end to create suction at the nozzle inlet and cause ambient air to enter the nozzle. The vortex flow in the nozzle causes the metal chip to segment and the segments thus formed to pass out of the discharge end of the nozzle where they are collected, cleaned and compacted as needed.

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2014 CFR

2014-07-01

... work fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2012 CFR

2012-07-01

... fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

37 CFR 211.5 - Deposit of identifying material.

Code of Federal Regulations, 2013 CFR

2013-07-01

... fixed in the form of the semiconductor chip product in which it was first commercially exploited. Defective chips may be deposited under this section provided that the mask work contribution would be revealed in reverse dissection of the chips. The four reproductions shall be accompanied by a visually...

Osteochondral repair in hemophilic ankle arthropathy: from current options to future perspectives

PubMed Central

BUDA, ROBERTO; CAVALLO, MARCO; CASTAGNINI, FRANCESCO; FERRANTI, ENRICO; NATALI, SIMONE; GIANNINI, SANDRO

2015-01-01

Young hemophilic patients are frequently affected by ankle arthropathy. At the end stage of the disease, the current treatments are arthrodesis and arthroplasty, which have significant drawbacks. Validated procedures capable of slowing down or even arresting the progression towards the end stage are currently lacking. This review aims to discuss the rationale for and feasibility of applying, in mild hemophilic ankle arthropathy, the main techniques currently used to treat osteochondral defects, focusing in particular on ankle distraction, chondrocyte implantation, mesenchymal stem cell transplantation, allograft transplantation and the use of growth factors. To date, ankle distraction is the only procedure that has been successfully used in hemophilic ankle arthropathy. The use of mesenchymal stem cells have recently been evaluated as feasible for osteochondral repair in hemophilic patients. There may be a rationale for the use of growth factors if they are combined with the previous techniques, which could be useful to arrest the progression of the degeneration or delay end-stage procedures. PMID:26904526

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... harmless extraneous vegetable material, stems, and portions thereof, blemishes, wrinkles, mutilated olives... to olives pitted along an axis other than the stem-flower axis. A defect is a unit where the angle of.... (12) Stem means a stem that measures 3 mm or more from the shoulder of the olive. Stems are classified...

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... harmless extraneous vegetable material, stems, and portions thereof, blemishes, wrinkles, mutilated olives... to olives pitted along an axis other than the stem-flower axis. A defect is a unit where the angle of.... (12) Stem means a stem that measures 3 mm or more from the shoulder of the olive. Stems are classified...

Dental Stem Cell Migration on Pulp Ceiling Cavities Filled with MTA, Dentin Chips, or Bio-Oss

PubMed Central

Lymperi, Stefania; Taraslia, Vasiliki; Tsatsoulis, Ioannis N.; Samara, Athina; Agrafioti, Anastasia; Anastasiadou, Ema; Kontakiotis, Evangelos

2015-01-01

MTA, Bio-Oss, and dentin chips have been successfully used in endodontics. The aim of this study was to assess the adhesion and migration of dental stem cells on human pulp ceiling cavities filled with these endodontic materials in an experimental model, which mimics the clinical conditions of regenerative endodontics. Cavities were formed, by a homemade mold, on untouched third molars, filled with endodontic materials, and observed with electron microscopy. Cells were seeded on cavities' surface and their morphology and number were analysed. The phenomenon of tropism was assessed in a migration assay. All three materials demonstrated appropriate microstructures for cell attachment. Cells grew on all reagents, but they showed a differential morphology. Moreover, variations were observed when comparing cells numbers on cavity's filling versus the surrounding dentine disc. The highest number of cells was recorded on dentin chips whereas the opposite was true for Bio-Oss. This was confirmed in the migration assay where a statistically significant lower number of cells migrated towards Bio-Oss as compared to MTA and dentin chips. This study highlights that MTA and dentin chips have a greater potential compared to Bio-Oss regarding the attraction of dental stem cells and are good candidates for bioengineered pulp regeneration. PMID:26146613

Bone marrow mesenchymal stem cells ameliorate inflammatory factor-induced dysfunction of INS-1 cells on chip.

PubMed

Sun, Yu; Yao, Zhina; Lin, Peng; Hou, Xinguo; Chen, Li

2014-05-01

Using a microfluidic chip, we have investigated whether bone marrow mesenchymal stem cells (BM-MSCs) could ameliorate IL-1β/IFN-γ-induced dysfunction of INS-1 cells. BM-MSCs were obtained from diabetes mellitus patients and their cell surface antigen expression profiles were analyzed by flow cytometric. INS-1 cells were cocultured with BM-MSCs on a microfluidic chip with persistent perfusion of medium containing 1 ng/mL IL-1β and 2.5 U/mL IFN-γ for 72 h. BM-MSCs could partially rescue INS-1 cells from cytokine-induced dysfunction and ameliorate the expression of insulin and PDX-1 gene in INS-1 cells. Thus BM-MSCs can be viewed as a promising stem cell source to depress inflammatory factor-induced dysfunction of pancreatic β cells in diabetic patients. © 2014 International Federation for Cell Biology.

Torrefaction of Yacon and Jerusalem Artichoke Stems as a Contribution to the Alternative Production of Inulin

NASA Astrophysics Data System (ADS)

Veselý, V.; Sobek, J.; Hanika, J.; Punčochář, M.

Recommendable torrefaction conditions were specified on the grounds of GT and DTA curves for the specimen of crushed stems of Yacon and Jerusalem artichoke. The impact of the size of crushed stems particle on the torrefaction process was monitored. The stem crushing process was optimized based on the results. We tested the effect of torrefaction performed on pellets made of raw material and wood chips, of which the pellets were made afterwards. It has been unambiguously proven that it was sensible to pelletize torrefied chips, otherwise the pellets were losing their coherence and crumbled. We calculated the fuel calorific value and its dependence on the residence time in the reactor. The economic benefit of torrefaction is that the power necessary for evaporation and leaching artichoke cuttings in water is obtained by combusting torrefied crushed stems.

Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP.

PubMed

Kanack, Adam J; Newsom, Oliver J; Scaglione, Kenneth Matthew

2018-02-23

The accumulation of misfolded proteins promotes protein aggregation and neuronal death in many neurodegenerative diseases. To counteract misfolded protein accumulation, neurons have pathways that recognize and refold or degrade aggregation-prone proteins. One U-box-containing E3 ligase, C terminus of Hsc70-interacting protein (CHIP), plays a key role in this process, targeting misfolded proteins for proteasomal degradation. CHIP plays a protective role in mouse models of neurodegenerative disease, and in humans, mutations in CHIP cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16), a fatal neurodegenerative disease characterized by truncal and limb ataxia that results in gait instability. Here, we systematically analyzed CHIP mutations that cause SCAR16 and found that most SCAR16 mutations destabilize CHIP. This destabilization caused mutation-specific defects in CHIP activity, including increased formation of soluble oligomers, decreased interactions with chaperones, diminished substrate ubiquitination, and reduced steady-state levels in cells. Consistent with decreased CHIP stability promoting its dysfunction in SCAR16, most mutant proteins recovered activity when the assays were performed below the mutants' melting temperature. Together, our results have uncovered the molecular basis of genetic defects in CHIP function that cause SCAR16. Our insights suggest that compounds that improve the thermostability of genetic CHIP variants may be beneficial for treating patients with SCAR16. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Chip-based comparison of the osteogenesis of human bone marrow- and adipose tissue-derived mesenchymal stem cells under mechanical stimulation.

PubMed

Park, Sang-Hyug; Sim, Woo Young; Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation.

Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation

PubMed Central

Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L.

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation. PMID:23029565

A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea.

PubMed

Campillo, Noelia; Jorba, Ignasi; Schaedel, Laura; Casals, Blai; Gozal, David; Farré, Ramon; Almendros, Isaac; Navajas, Daniel

2016-01-01

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

Silicon-on-insulator sensors using integrated resonance-enhanced defect-mediated photodetectors.

PubMed

Fard, Sahba Talebi; Murray, Kyle; Caverley, Michael; Donzella, Valentina; Flueckiger, Jonas; Grist, Samantha M; Huante-Ceron, Edgar; Schmidt, Shon A; Kwok, Ezra; Jaeger, Nicolas A F; Knights, Andrew P; Chrostowski, Lukas

2014-11-17

A resonance-enhanced, defect-mediated, ring resonator photodetector has been implemented as a single unit biosensor on a silicon-on-insulator platform, providing a cost effective means of integrating ring resonator sensors with photodetectors for lab-on-chip applications. This method overcomes the challenge of integrating hybrid photodetectors on the chip. The demonstrated responsivity of the photodetector-sensor was 90 mA/W. Devices were characterized using refractive index modified solutions and showed sensitivities of 30 nm/RIU.

Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis.

PubMed

González-García, Mary-Paz; Pavelescu, Irina; Canela, Andrés; Sevillano, Xavier; Leehy, Katherine A; Nelson, Andrew D L; Ibañes, Marta; Shippen, Dorothy E; Blasco, Maria A; Caño-Delgado, Ana I

2015-05-12

Telomeres are specialized nucleoprotein caps that protect chromosome ends assuring cell division. Single-cell telomere quantification in animals established a critical role for telomerase in stem cells, yet, in plants, telomere-length quantification has been reported only at the organ level. Here, a quantitative analysis of telomere length of single cells in Arabidopsis root apex uncovered a heterogeneous telomere-length distribution of different cell lineages showing the longest telomeres at the stem cells. The defects in meristem and stem cell renewal observed in tert mutants demonstrate that telomere lengthening by TERT sets a replicative limit in the root meristem. Conversely, the long telomeres of the columella cells and the premature stem cell differentiation plt1,2 mutants suggest that differentiation can prevent telomere erosion. Overall, our results indicate that telomere dynamics are coupled to meristem activity and continuous growth, disclosing a critical association between telomere length, stem cell function, and the extended lifespan of plants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dynamics of cells function on laser cell-chip system

NASA Astrophysics Data System (ADS)

Kushibiki, Toshihiro; Sano, Tomoko; Ishii, Katsunori; Yoshihashi-Suzuki, Sachiko; Awazu, Kunio

2006-02-01

A new type of cell-cultivation system based on laser processing has been developed for the on-chip cultivation of living cells. We introduce a "laser cell-chip", on which migration of cells, such as stem cells, tumor cells or immunocompetent cells, can be observed. A sheet prepared from epoxy resin was processed by KrF excimer laser (248 nm, 1.6 J/cm2) for preparation of microgrooved surfaces with various groove width, spacing, and depth. A laser cell-chip can make kinetic studies of cell migration depending on the concentration gradient of a chemoattractant. In this study, megakaryocytes were used for the migration on a groove of laser cell-chip by the concentration gradient of the stromal cell derived factor 1 (SDF-1/CXCL12). SDF-1/CXCL12 plays an important and unique role in the regulation of stem/progenitor cell trafficking. A megakaryocyte was migrated on a groove of laser cell-chip depending on the optical concentration gradient of SDF-1/CXCL12. Since SDF-1/CXCL12-induced migration of mature megakaryocyte was known to increase the platelet production in the bone marrow extravascular space, the diagnosis of cell migration on laser cell-chip could provide a new strategy to potentially reconstitute hematopoiesis and avoid life-threatening hemorrhage after myelosuppression or bone marrow failure.

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... to the degree of freedom from harmless extraneous vegetable material, stems, and portions thereof... the stem-flower axis. A defect is a unit where the angle of these two axes exceeds 45 degrees. (5... pitted olive equal to or exceeding the area of a circle 5 mm in diameter. (12) Stem means a stem that...

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... to the degree of freedom from harmless extraneous vegetable material, stems, and portions thereof... the stem-flower axis. A defect is a unit where the angle of these two axes exceeds 45 degrees. (5... pitted olive equal to or exceeding the area of a circle 5 mm in diameter. (12) Stem means a stem that...

Cell Patterning Chip for Controlling the Stem Cell Microenvironment

PubMed Central

Rosenthal, Adam; Macdonald, Alice; Voldman, Joel

2007-01-01

Cell-cell signaling is an important component of the stem cell microenvironment, affecting both differentiation and self-renewal. However, traditional cell-culture techniques do not provide precise control over cell-cell interactions, while existing cell patterning technologies are limited when used with proliferating or motile cells. To address these limitations, we created the Bio Flip Chip (BFC), a microfabricated polymer chip containing thousands of microwells, each sized to trap down to a single stem cell. We have demonstrated the functionality of the BFC by patterning a 50×50 grid of murine embryonic stem cells (mESCs), with patterning efficiencies > 75%, onto a variety of substrates – a cell-culture dish patterned with gelatin, a 3-D substrate, and even another layer of cells. We also used the BFC to pattern small groups of cells, with and without cell-cell contact, allowing incremental and independent control of contact-mediated signaling. We present quantitative evidence that cell-cell contact plays an important role in depressing mESC colony formation, and show that E-cadherin is involved in this negative regulatory pathway. Thus, by allowing exquisite control of the cellular microenvironment, we provide a technology that enables new applications in tissue engineering and regenerative medicine. PMID:17434582

Engraftment of donor mesenchymal stem cells in chimeric BXSB includes vascular endothelial cells and hepatocytes.

PubMed

Jones, Olcay Y; Gok, Faysal; Rushing, Elisabeth J; Horkayne-Szakaly, Iren; Ahmed, Atif A

2011-01-01

Somatic tissue engraftment was studied in BXSB mice treated with mesenchymal stem cell transplantation. Hosts were conditioned with nonlethal radiation prior to introducing donor cells from major histocompatibility complex-matched green fluorescent protein transgenic mice. Transplant protocols differed for route of injection, ie, intravenous (i.v.) versus intraperitoneal (i.p.), and source of mesenchymal stem cells, ie, unfractionated bone marrow cells, ex vivo expanded mesenchymal stem cells, or bone chips. Tissue chimerism was determined after short (10-12 weeks) or long (62 weeks) posttransplant follow-up by immunohistochemistry for green fluorescent protein. Engraftment of endothelial cells was seen in several organs including liver sinusoidal cells in i.v. treated mice with ex vivo expanded mesenchymal stem cells or with unfractionated bone marrow cells. Periportal engraftment of liver hepatocytes, but not engraftment of endothelial cells, was found in mice injected i.p. with bone chips. Engraftment of adipocytes was a common denominator in both i.v. and i.p. routes and occurred during early phases post-transplant. Disease control was more robust in mice that received both i.v. bone marrow and i.p. bone chips compared to mice that received i.v. bone marrow alone. Thus, the data support potential use of mesenchymal stem cell transplant for treatment of severe lupus. Future studies are needed to optimize transplant conditions and tailor protocols that may in part be guided by fat and endothelial biomarkers. Furthermore, the role of liver chimerism in disease control and the nature of cellular communication among donor hematopoietic and mesenchymal stem cells in a chimeric host merit further investigation.

Pattern of defect associated with stem stubs on northern hardwoods

Treesearch

Alex L. Shigo

1965-01-01

Decay and discoloration are the principal defects that reduce quality of northern hardwoods in New England. We need to know how to minimize these defects in young growing stock, and how to recognize them in merchantable trees. To determine accurately the amount of internal defect in trees, we must know the quantitative relationships between external signs on stems and...

Epigenome analysis of pluripotent stem cells

PubMed Central

Ricupero, Christopher L.; Swerdel, Mavis R.; Hart, Ronald P.

2015-01-01

Summary Mis-regulation of gene expression due to epigenetic abnormalities has been linked with complex genetic disorders, psychiatric illness and cancer. In addition, the dynamic epigenetic changes that occur in pluripotent stem cells are believed to impact regulatory networks essential for proper lineage development. Chromatin immunoprecipitation (ChIP) is a technique used to isolate and enrich chromatin fragments using antibodies against specific chromatin modifications, such as DNA binding proteins or covalent histone modifications. Until recently, many ChIP protocols required millions of cells for each immunoprecipitation. This severely limited analysis of rare cell populations or post-mitotic, differentiated cell lines. Here, we describe a low cell number ChIP protocol with next generation sequencing and analysis, that has the potential to uncover novel epigenetic regulatory pathways that were previously difficult or impossible to obtain. PMID:23546758

Healing bone lesion defects using injectable CaSO4 /CaPO4 -TCP bone graft substitute compared to cancellous allograft bone chips in a canine model.

PubMed

Hall, Deborah J; Turner, Thomas M; Urban, Robert M

2018-04-16

CaSO 4 /CaPO 4 -TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical-size axial defect created bilaterally into the proximal humerus. CaSO 4 /CaPO 4 -TCP bone graft substitute (PRO-DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze-dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann-Whitney tests. There was more bone in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO 4 /CaPO 4 -TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO 4 /CaPO 4 -TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze-dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

Potential Application of BIOMASS Technology at National Space Technology Laboratories and Mississippi Army Ammunition Plant.

DTIC Science & Technology

1980-02-01

fuel. Based on the survey data, wood chips in the NSTL area are sold for $13 to $16 per wet ton ($14 to $18 Der l03 kg wet), bark for $6 to $7 per wet...truck 3 Chip vans (initially) 1 Pickup (3/4 ton) 1 Front-end loader (for handling at chip pile) This equipment combination assumes all material ]-inch...ing sites in chip vans , preferably with live-beds to aid in unloading. At the processing site the chips would be stored in large piles. A Front-end

Stem cells applications in bone and tooth repair and regeneration: New insights, tools, and hopes.

PubMed

Abdel Meguid, Eiman; Ke, Yuehai; Ji, Junfeng; El-Hashash, Ahmed H K

2018-03-01

The exploration of stem and progenitor cells holds promise for advancing our understanding of the biology of tissue repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different tissue-species defects or disorders such as bone, cartilages, and tooth defects or disorders. Bone is a specialized connective tissue, with mineralized extracellular components that provide bones with both strength and rigidity, and thus enable bones to function in body mechanical supports and necessary locomotion process. New insights have been added to the use of different types of stem cells in bone and tooth defects over the last few years. In this concise review, we briefly describe bone structure as well as summarize recent research progress and accumulated information regarding the osteogenic differentiation of stem cells, as well as stem cell contributions to bone repair/regeneration, bone defects or disorders, and both restoration and regeneration of bones and cartilages. We also discuss advances in the osteogenic differentiation and bone regeneration of dental and periodontal stem cells as well as in stem cell contributions to dentine regeneration and tooth engineering. © 2017 Wiley Periodicals, Inc.

An open-architecture approach to defect analysis software for mask inspection systems

NASA Astrophysics Data System (ADS)

Pereira, Mark; Pai, Ravi R.; Reddy, Murali Mohan; Krishna, Ravi M.

2009-04-01

Industry data suggests that Mask Inspection represents the second biggest component of Mask Cost and Mask Turn Around Time (TAT). Ever decreasing defect size targets lead to more sensitive mask inspection across the chip, thus generating too many defects. Hence, more operator time is being spent in analyzing and disposition of defects. Also, the fact that multiple Mask Inspection Systems and Defect Analysis strategies would typically be in use in a Mask Shop or a Wafer Foundry further complicates the situation. In this scenario, there is a need for a versatile, user friendly and extensible Defect Analysis software that reduces operator analysis time and enables correct classification and disposition of mask defects by providing intuitive visual and analysis aids. We propose a new vendor-neutral defect analysis software, NxDAT, based on an open architecture. The open architecture of NxDAT makes it easily extensible to support defect analysis for mask inspection systems from different vendors. The capability to load results from mask inspection systems from different vendors either directly or through a common interface enables the functionality of establishing correlation between inspections carried out by mask inspection systems from different vendors. This capability of NxDAT enhances the effectiveness of defect analysis as it directly addresses the real-life scenario where multiple types of mask inspection systems from different vendors co-exist in mask shops or wafer foundries. The open architecture also potentially enables loading wafer inspection results as well as loading data from other related tools such as Review Tools, Repair Tools, CD-SEM tools etc, and correlating them with the corresponding mask inspection results. A unique concept of Plug-In interface to NxDAT further enhances the openness of the architecture of NxDAT by enabling end-users to add their own proprietary defect analysis and image processing algorithms. The plug-in interface makes it possible for the end-users to make use of their collected knowledge through the years of experience in mask inspection process by encapsulating the knowledge into software utilities and plugging them into NxDAT. The plug-in interface is designed with the intent of enabling the pro-active mask defect analysis teams to build competitive differentiation into their defect analysis process while protecting their knowledge internally within their company. By providing interface with all major standard layout and mask data formats, NxDAT enables correlation of defect data on reticles with design and mask databases, further extending the effectiveness of defect analysis for D2DB inspection. NxDAT also includes many other advanced features for easy and fast navigation, visual display of defects, defect selection, multi-tier classification, defect clustering and gridding, sophisticated CD and contact measurement analysis, repeatability analysis such as adder analysis, defect trend, capture rate etc.

Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).

PubMed

Bastepe, Murat; Altug-Teber, Ozge; Agarwal, Chhavi; Oberfield, Sharon E; Bonin, Michael; Jüppner, Harald

2011-03-01

Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. Copyright © 2010 Elsevier Inc. All rights reserved.

Is bone transplantation the gold standard for repair of alveolar bone defects?

PubMed

Raposo-Amaral, Cassio Eduardo; Bueno, Daniela Franco; Almeida, Ana Beatriz; Jorgetti, Vanda; Costa, Cristiane Cabral; Gouveia, Cecília Helena; Vulcano, Luiz Carlos; Fanganiello, Roberto D; Passos-Bueno, Maria Rita; Alonso, Nivaldo

2014-01-01

New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate), compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7) defects were repaired with autogenous bone grafts; Group 2 (n = 5) defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5) defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5) defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6) defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2-5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01) and 38.35% ± 19.59% (p = 0.06) of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30) and 61.80% ± 2.14% (p = 0.88) of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation

PubMed Central

Jones, Morgan; Osawa, Gail; Regal, Joshua A.; Weinberg, Daniel N.; Taggart, James; Kocak, Hande; Friedman, Ann; Ferguson, David O.; Keegan, Catherine E.; Maillard, Ivan

2013-01-01

The shelterin complex plays dual functions in telomere homeostasis by recruiting telomerase and preventing the activation of a DNA damage response at telomeric ends. Somatic stem cells require telomerase activity, as evidenced by progressive stem cell loss leading to bone marrow failure in hereditary dyskeratosis congenita. Recent work demonstrates that dyskeratosis congenita can also arise from mutations in specific shelterin genes, although little is known about shelterin functions in somatic stem cells. We found that mouse hematopoietic stem cells (HSCs) are acutely sensitive to inactivation of the shelterin gene Acd, encoding TPP1. Homozygosity for a hypomorphic acd allele preserved the emergence and expansion of fetal HSCs but led to profoundly defective function in transplantation assays. Upon complete Acd inactivation, HSCs expressed p53 target genes, underwent cell cycle arrest, and were severely depleted within days, leading to hematopoietic failure. TPP1 loss induced increased telomeric fusion events in bone marrow progenitors. However, unlike in epidermal stem cells, p53 deficiency did not rescue TPP1-deficient HSCs, indicating that shelterin dysfunction has unique effects in different stem cell populations. Because the consequences of telomere shortening are progressive and unsynchronized, acute loss of shelterin function represents an attractive alternative for studying telomere crisis in hematopoietic progenitors. PMID:24316971

The MRI appearances of cancellous allograft bone chips after the excision of bone tumours.

PubMed

Kang, S; Han, I; Hong, S H; Cho, H S; Kim, W; Kim, H-S

2015-01-01

Cancellous allograft bone chips are commonly used in the reconstruction of defects in bone after removal of benign tumours. We investigated the MRI features of grafted bone chips and their change over time, and compared them with those with recurrent tumour. We retrospectively reviewed 66 post-operative MRIs from 34 patients who had undergone curettage and grafting with cancellous bone chips to fill the defect after excision of a tumour. All grafts showed consistent features at least six months after grafting: homogeneous intermediate or low signal intensities with or without scattered hyperintense foci (speckled hyperintensities) on T1 images; high signal intensities with scattered hypointense foci (speckled hypointensities) on T2 images, and peripheral rim enhancement with or without central heterogeneous enhancements on enhanced images. Incorporation of the graft occurred from the periphery to the centre, and was completed within three years. Recurrent lesions consistently showed the same signal intensities as those of pre-operative MRIs of the primary lesions. There were four misdiagnoses, three of which were chondroid tumours. We identified typical MRI features and clarified the incorporation process of grafted cancellous allograft bone chips. The most important characteristics of recurrent tumours were that they showed the same signal intensities as the primary tumours. It might sometimes be difficult to differentiate grafted cancellous allograft bone chips from a recurrent chondroid tumour. ©2015 The British Editorial Society of Bone & Joint Surgery.

Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

PubMed

Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

2017-06-01

Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P < .01). Furthermore, the ACC group had significantly less fibrous tissue (23.8%) compared with the MST group (41.1%) ( P < .01). No significant difference in fibrocartilage content was found (54.7% for ACC vs 50.8% for MST). The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment ( P < .05). The ACC-treated defects had significantly more collagen type II staining (54.5%) compared with the MST-treated defects (28.1%) ( P < .05). ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

Repair of full-thickness cartilage defects with cells of different origin in a rabbit model.

PubMed

Yan, Hui; Yu, Changlong

2007-02-01

The purpose of this study was to evaluate the repaired tissues formed in full-thickness cartilage defects in a rabbit model implanted with 4 types of chondrogenic cells, including chondrocytes, mesenchymal stem cells (MSCs) and fibroblasts from rabbit, and human umbilical cord blood (hUCB) stem cells. Chondrocytes, MSCs, and fibroblasts were isolated from 6-week-old New Zealand rabbits; hUCB stem cells were isolated from the umbilical cord blood of newborn children. These 4 types of cells were cultured in vitro and embedded in polylactic acid (PLA) matrices. Full-thickness defects were produced in the femoral trochlear grooves of both knees in 36 adult New Zealand White rabbits. Cell/PLA composites were transplanted into cartilage defects. A total of 5 groups were formed according to implanted cell type: Group A, chondrocytes; Group B, MSCs; Group C, fibroblasts; Group D, hUCB stem cells; and Group E, no cells (control group). Repaired tissues were evaluated grossly, histologically, and immunohistochemically at 6 weeks and 12 weeks after implantation. In Groups A and B, defects were repaired with hyaline-like cartilage. In Group C, defects were repaired with fibrous tissue. In Group D, defects were repaired primarily with fibrous tissue and scattered chondrocytes; in some specimens, defects were repaired with a thin layer of hyaline-like cartilage at 12 weeks. In Group E, defects were repaired with fibrous tissue. Histologic scores in Groups A and B were significantly higher than those in Groups C, D, and E at 6 and 12 weeks after transplantation. Full-thickness cartilage defects treated with chondrocyte or MSC transplantation were repaired with hyaline-like cartilage tissue, and repair was significantly better than in tissues treated with fibroblasts and hUCB stem cells, as well as in the control group. Repaired tissues treated with MSCs appeared to have better cell arrangement, subchondral bone remodeling, and integration with surrounding cartilage than did repaired tissues generated by chondrocyte implantation. MSCs might be the most suitable cell source for cartilage repair. Further investigation into hUCB stem cell transplantation is needed. In our study of rabbits, MSCs supplied the most promising cell source for cartilage repair.

Human bone perivascular niche-on-a-chip for studying metastatic colonization.

PubMed

Marturano-Kruik, Alessandro; Nava, Michele Maria; Yeager, Keith; Chramiec, Alan; Hao, Luke; Robinson, Samuel; Guo, Edward; Raimondi, Manuela Teresa; Vunjak-Novakovic, Gordana

2018-02-06

Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.

Transcript Profiling of Two Alfalfa Genotypes with Contrasting Cell Wall Composition in Stems Using a Cross-Species Platform: Optimizing Analysis by Masking Biased Probes

USDA-ARS?s Scientific Manuscript database

The stem cell walls of alfalfa [Medicago sativa (L.) ssp. sativa] genotype 252 have high cellulose and lignin concentrations, while stem cell walls of genotype 1283 have low cellulose and lignin concentrations. The GeneChip® Medicago Genome Array, developed for Medicago truncatula, is a suitable pla...

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

PubMed Central

Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients. PMID:28798878

Fault Tolerant Cache Schemes

NASA Astrophysics Data System (ADS)

Tu, H.-Yu.; Tasneem, Sarah

Most of modern microprocessors employ on—chip cache memories to meet the memory bandwidth demand. These caches are now occupying a greater real es tate of chip area. Also, continuous down scaling of transistors increases the possi bility of defects in the cache area which already starts to occupies more than 50% of chip area. For this reason, various techniques have been proposed to tolerate defects in cache blocks. These techniques can be classified into three different cat egories, namely, cache line disabling, replacement with spare block, and decoder reconfiguration without spare blocks. This chapter examines each of those fault tol erant techniques with a fixed typical size and organization of L1 cache, through extended simulation using SPEC2000 benchmark on individual techniques. The de sign and characteristics of each technique are summarized with a view to evaluate the scheme. We then present our simulation results and comparative study of the three different methods.

Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

PubMed

Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

2017-01-01

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip

PubMed Central

Musah, Samira; Mammoto, Akiko; Ferrante, Thomas C.; Jeanty, Sauveur S. F.; Hirano-Kobayashi, Mariko; Mammoto, Tadanori; Roberts, Kristen; Chung, Seyoon; Novak, Richard; Ingram, Miles; Fatanat-Didar, Tohid; Koshy, Sandeep; Weaver, James C.; Church, George M.; Ingber, Donald E.

2017-01-01

An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications. PMID:29038743

On-chip immobilization of planarians for in vivo imaging.

PubMed

Dexter, Joseph P; Tamme, Mary B; Lind, Christine H; Collins, Eva-Maria S

2014-09-17

Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra.

On-chip immobilization of planarians for in vivo imaging

PubMed Central

Dexter, Joseph P.; Tamme, Mary B.; Lind, Christine H.; Collins, Eva-Maria S.

2014-01-01

Planarians are an important model organism for regeneration and stem cell research. A complete understanding of stem cell and regeneration dynamics in these animals requires time-lapse imaging in vivo, which has been difficult to achieve due to a lack of tissue-specific markers and the strong negative phototaxis of planarians. We have developed the Planarian Immobilization Chip (PIC) for rapid, stable immobilization of planarians for in vivo imaging without injury or biochemical alteration. The chip is easy and inexpensive to fabricate, and worms can be mounted for and removed after imaging within minutes. We show that the PIC enables significantly higher-stability immobilization than can be achieved with standard techniques, allowing for imaging of planarians at sub-cellular resolution in vivo using brightfield and fluorescence microscopy. We validate the performance of the PIC by performing time-lapse imaging of planarian wound closure and sequential imaging over days of head regeneration. We further show that the device can be used to immobilize Hydra, another photophobic regenerative model organism. The simple fabrication, low cost, ease of use, and enhanced specimen stability of the PIC should enable its broad application to in vivo studies of stem cell and regeneration dynamics in planarians and Hydra. PMID:25227263

The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

PubMed

Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

2015-01-15

Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. © 2015 Froldi et al.; Published by Cold Spring Harbor Laboratory Press.

Prototyping of Silicon Strip Detectors for the Inner Tracker of the ALICE Experiment

NASA Astrophysics Data System (ADS)

Sokolov, Oleksiy

2006-04-01

The ALICE experiment at CERN will study heavy ion collisions at a center-of-mass energy 5.5˜TeV per nucleon. Particle tracking around the interaction region at radii r<45 cm is done by the Inner Tracking System (ITS), consisting of six cylindrical layers of silicon detectors. The outer two layers of the ITS use double-sided silicon strip detectors. This thesis focuses on testing of these detectors and performance studies of the detector module prototypes at the beam test. Silicon strip detector layers will require about 20 thousand HAL25 front-end readout chips and about 3.5 thousand hybrids each containing 6 HAL25 chips. During the assembly procedure, chips are bonded on a patterned TAB aluminium microcables which connect to all the chip input and output pads, and then the chips are assembled on the hybrids. Bonding failures at the chip or hybrid level may either render the component non-functional or deteriorate its the performance such that it can not be used for the module production. After each bonding operation, the component testing is done to reject the non-functional or poorly performing chips and hybrids. The LabView-controlled test station for this operation has been built at Utrecht University and was successfully used for mass production acceptance tests of chips and hybrids at three production labs. The functionality of the chip registers, bonding quality and analogue functionality of the chips and hybrids are addressed in the test. The test routines were optimized to minimize the testing time to make sure that testing is not a bottleneck of the mass production. For testing of complete modules the laser scanning station with 1060 nm diode laser has been assembled at Utrecht University. The testing method relies of the fact that a response of the detector module to a short collimated laser beam pulse resembles a response to a minimum ionizing particle. A small beam spot size (˜7 μm ) allows to deposit the charge in a narrow region and measure the response of individual detector channels. First several module prototypes have been studied with this setup, the strip gain and charge sharing function have been measured, the later is compared with the model predictions. It was also shown that for a laser beam of a high monochromaticity, interference in the sensor bulk significantly modulates the deposited charge and introduces a systematic error of the gain measurement. Signatures of disconnected strips and pinholes defects have been observed, the response of the disconnected strips to the laser beam has been correlated with the noise measurements. Beam test of four prototype modules have been carried out at PS accelerator at CERN using 7 GeV/c pions. It was demonstrated that the modules provide an excellent signal-to-noise ratio in the range 40-75. The estimated spatial resolution for the normally incident tracks is about 18 μm using the center-of-gravity cluster reconstruction method. A non-iterative method for spatial resolution determination was developed, it was shown that in order to determine the resolution of each individual detector in the telescope, the telescope should consist of at least 5 detectors. The detectors showed high detection efficiency, in the order 99%. It was shown that the particle loss occurs mostly in the defected regions near the noisy strips or strips with a very low gain. The efficiency of the sensor area with nominal characteristics is consistent with 100%.

Multi-modal STEM-based tomography of HT-9 irradiated in FFTF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Kevin G.; Eftink, Benjamin Paul; Saleh, Tarik A.

Under irradiation, point defects and defect clusters can agglomerate to form extended two and three dimensional (2D/3D) defects. The formation of defects can be synergistic in nature with one defect or defect-type influencing the formation and/or evolution of another. The resul is a need exists to perform advanced characterization where microstructures are accurately reproduced in 3D. Here, HT-9 neutron irradiated in the FFTF was used to evaluate the ability of multi-tilt STEM-based tomography to reproduce the fine-scale radiation-induced microstructure. High-efficiency STEM-EDS was used to provide both structural and chemical information during the 3D reconstruction. The results show similar results tomore » a previous two-tilt tomography study on the same material; the α' phase is denuded around the Ni-Si-Mn rich G-phase and cavities. It is concluded both tomography reconstruction techniques are readily viable and could add significant value to the advanced characterization capabilities for irradiated materials.« less

Searching for a New Improved Atlantic in ‘Atlantic’ and ‘Superior’ Reciprocal Cross Populations

USDA-ARS?s Scientific Manuscript database

‘Atlantic’ is the standard variety for chipping from the field or very short-term cold storage. It has traits desired by the chip industry such as uniformity, high specific gravity and high yield. However, ‘Atlantic’ tubers are susceptible to common scab and internal defects such as internal brown s...

Performance of promising clones from Atlantic x Superior and Superior x Snowden populations evaluated in several locations

USDA-ARS?s Scientific Manuscript database

Atlantic is the standard variety for chipping from the field or very short-term cold storage. It has traits desired by the chip industry such as uniformity, high specific gravity and high yield. However, Atlantic tubers are susceptible to common scab and internal defects such as internal brown spot,...

Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma.

PubMed

Nair, Manitha B; Varma, H K; Menon, K V; Shenoy, Sachin J; John, Annie

2009-06-01

Segmental bone defects resulting from trauma or pathology represent a common and significant clinical problem. In this study, a triphasic ceramic (calcium silicate, hydroxyapatite and tricalcium phosphate)-coated hydroxyapatite (HASi) having the benefits of both HA (osteointegration, osteoconduction) and silica (degradation) was used as a bone substitute for the repair of segmental defect (2 cm) created in a goat femur model. Three experimental goat femur implant groups--(a) bare HASi, (b) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi (HASi+C) and (c) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi+platelet-rich plasma (HASi+CP)--were designed and efficacy performance in the healing of the defect was evaluated. In all the groups, the material united with host bone without any inflammation and an osseous callus formed around the implant. This reflects the osteoconductivity of HASi where the cells have migrated from the cut ends of host bone. The most observable difference between the groups appeared in the mid region of the defect. In bare HASi groups, numerous osteoblast-like cells could be seen together with a portion of material. However, in HASi+C and HASi+CP, about 60-70% of that area was occupied by woven bone, in line with material degradation. The interconnected porous nature (50-500 microm), together with the chemical composition of the HASi, facilitated the degradation of HASi, thereby opening up void spaces for cellular ingrowth and bone regeneration. The combination of HASi with cells and PRP was an added advantage that could promote the expression of many osteoinductive proteins, leading to faster bone regeneration and material degradation. Based on these results, we conclude that bare HASi can aid in bone regeneration but, with the combination of cells and PRP, the sequence of healing events are much faster in large segmental bone defects in weight-bearing areas in goats.

Stem cell homing-based tissue engineering using bioactive materials

NASA Astrophysics Data System (ADS)

Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

2017-06-01

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

Stem Cell Therapies for Knee Cartilage Repair: The Current Status of Preclinical and Clinical Studies

PubMed Central

Anderson, John A.; Little, Dianne; Toth, Alison P.; Moorman, Claude T.; Tucker, Bradford S.; Ciccotti, Michael G.; Guilak, Farshid

2014-01-01

Background Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future. Purpose The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects. Study Design Literature review. Methods A PubMed search was undertaken. The key phrase “stem cells and knee” was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and “stem cells and knee” was used as the search phrase. Results Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials. Conclusion The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee’s cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair. PMID:24220016

Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage.

PubMed

Zhang, Hai-Ning; Li, Lei; Leng, Ping; Wang, Ying-Zhen; Lv, Cheng-Yu

2009-04-01

To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects. Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro. Twenty-seven New Zealand white rabbits were divided into three groups randomly. The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint, and the defects repaired with gel or without treatment served as control groups. After 4, 8 and 12 weeks, the reconstructed tissue was evaluated macroscopically and microscopically. Histological analysis and qualitative scoring were also performed to detect the outcome. Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived tissue. The result was better in ADSCs group than the control ones. The microstructure of reconstructed tissue with ADSCs was similar to that of hyaline cartilage and contained more cells and regular matrix fibers, being better than other groups. Plenty of collagen fibers around cells could be seen under transmission electron microscopy. Statistical analysis revealed a significant difference in comparison with other groups at each time point (t equal to 4.360, P less than 0.01). These results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects.

SHORT-ROOT regulates vascular patterning, but not apical meristematic activity in the Arabidopsis root through cytokinin homeostasis

PubMed Central

Hao, Yueling; Cui, Hongchang

2012-01-01

SHORT-ROOT (SHR) is a key regulator of radial patterning and stem-cell renewal in the Arabidopsis root. Although SHR is expressed in the stele, its function in the vascular tissue was not recognized until recently. In shr, the protoxylem is missing due to the loss of expression of microRNA165A (miR165A) and microRNA166B (miR165B). shr is also defective in lateral root formation, but the mechanism remains unclear. To dissect the SHR developmental pathway, we recently have identified its direct targets at the genome scale by chromatin immunoprecipitation followed by microarray analysis (ChIP-chip). In further studies, we have shown that SHR regulates cytokinin homeostasis through cytokinin oxidase 3 and that this role of SHR is critical to vascular patterning in the root. In this communication we report that SHR also regulates miR165A and miR166B indirectly through its effect on cytokinin homeostasis. Although cytokinin is inhibitory to root growth, the root-apical-meristem defect in shr was not alleviated by reduction of endogenous cytokinin. These results together suggest that SHR regulates vascular patterning, but not root apical meristematic activity, through cytokinin homeostasis. PMID:22476466

Evaluation of crystallographic strain, rotation and defects in functional oxides by the moiré effect in scanning transmission electron microscopy.

PubMed

Naden, A B; O'Shea, K J; MacLaren, D A

2018-04-20

Moiré patterns in scanning transmission electron microscopy (STEM) images of epitaxial perovskite oxides are used to assess strain and defect densities over fields of view extending over several hundred nanometers. The patterns arise from the geometric overlap of the rastered STEM electron beam and the samples' crystal periodicities and we explore the emergence and application of these moiré fringes for rapid strain analysis. Using the epitaxial functional oxide perovskites BiFeO 3 and Pr 1-x Ca x MnO 3 , we discuss the impact of large degrees of strain on the quantification of STEM moiré patterns, identify defects in the fringe patterns and quantify strain and lattice rotation. Such a wide-area analysis of crystallographic strain and defects is crucial for developing structure-function relations of functional oxides and we find the STEM moiré technique to be an attractive means of structural assessment that can be readily applied to low dose studies of damage sensitive crystalline materials.

Evaluation of crystallographic strain, rotation and defects in functional oxides by the moiré effect in scanning transmission electron microscopy

NASA Astrophysics Data System (ADS)

Naden, A. B.; O'Shea, K. J.; MacLaren, D. A.

2018-04-01

Moiré patterns in scanning transmission electron microscopy (STEM) images of epitaxial perovskite oxides are used to assess strain and defect densities over fields of view extending over several hundred nanometers. The patterns arise from the geometric overlap of the rastered STEM electron beam and the samples’ crystal periodicities and we explore the emergence and application of these moiré fringes for rapid strain analysis. Using the epitaxial functional oxide perovskites BiFeO3 and Pr1-x Ca x MnO3, we discuss the impact of large degrees of strain on the quantification of STEM moiré patterns, identify defects in the fringe patterns and quantify strain and lattice rotation. Such a wide-area analysis of crystallographic strain and defects is crucial for developing structure-function relations of functional oxides and we find the STEM moiré technique to be an attractive means of structural assessment that can be readily applied to low dose studies of damage sensitive crystalline materials.

Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report.

PubMed

Liu, Yihong; Liu, Yuchen; Wang, Pujie; Tian, Haoming; Ai, Jianzhong; Liu, Yangbo; Zhou, Yi; Liu, Zhongwen; Guo, Wenjun; Yang, Shenke

2014-06-01

Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.

C-terminus of HSC70-Interacting Protein (CHIP) Inhibits Adipocyte Differentiation via Ubiquitin- and Proteasome-Mediated Degradation of PPARγ

PubMed Central

Kim, Jung-Hoon; Shin, Soyeon; Seo, Jinho; Lee, Eun-Woo; Jeong, Manhyung; Lee, Min-sik; Han, Hyun-Ji; Song, Jaewhan

2017-01-01

PPARγ (Peroxisome proliferator-activated receptor γ) is a nuclear receptor involved in lipid homeostasis and related metabolic diseases. Acting as a transcription factor, PPARγ is a master regulator for adipocyte differentiation. Here, we reveal that CHIP (C-terminus of HSC70-interacting protein) suppresses adipocyte differentiation by functioning as an E3 ligase of PPARγ. CHIP directly binds to and induces ubiquitylation of the PPARγ protein, leading to proteasome-dependent degradation. Stable overexpression or knockdown of CHIP inhibited or promoted adipogenesis, respectively, in 3T3-L1 cells. On the other hand, a CHIP mutant defective in E3 ligase could neither regulate PPARγ protein levels nor suppress adipogenesis, indicating the importance of CHIP-mediated ubiquitylation of PPARγ in adipocyte differentiation. Lastly, a CHIP null embryo fibroblast exhibited augmented adipocyte differentiation with increases in PPARγ and its target protein levels. In conclusion, CHIP acts as an E3 ligase of PPARγ, suppressing PPARγ-mediated adipogenesis. PMID:28059128

Success of Maxillary Alveolar Defect Repair in Rats Using Osteoblast-Differentiated Human Deciduous Dental Pulp Stem Cells.

PubMed

Jahanbin, Arezoo; Rashed, Roozbeh; Alamdari, Daryoush Hamidi; Koohestanian, Niloufar; Ezzati, Atefeh; Kazemian, Mojgan; Saghafi, Shadi; Raisolsadat, Mohammad Ali

2016-04-01

The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response in craniofacial abnormalities. The main aim of this study was to evaluate the regenerative potential of human dental pulp stem cells, isolated from deciduous teeth, for reconstructing maxillary alveolar defects in Wistar rats. Human deciduous dental pulp stem cells were isolated and stimulated to differentiate into osteoblasts in culture media. Maxillary alveolar defects were created in 60 Wistar rats by a surgical procedure. Then, on the basis of the type of graft used to repair the bone defect, the rats were divided into 6 equal groups: groups 1 and 2, transplantation of iliac bone graft; groups 3 and 4, transplantation of stem cells derived from deciduous dental pulp in addition to collagen matrix; groups 5 and 6, transplantation of just collagen matrix. Then, fetal bone formation, granulation tissue, fibrous tissue, and inflammatory tissue were evaluated by hematoxylin-eosin staining at 1 month (groups 1, 3, and 5) and 2 months (groups 2, 4, and 6) after surgery, and data were analyzed and compared using the Fisher exact test. Maximum fetal bone formation occurred in group 2, in which iliac bone graft was inserted into the defect area for 2 months; there also were significant differences among the groups for bone formation (P = .009). In the 1-month groups, there were no significant differences between the control and stem cell-plus-scaffold groups. There were significant differences between the 2-month groups for fetal bone formation only between the control and scaffold groups (P = .026). The study showed that human dental pulp stem cells are an additional cell resource for repairing maxillary alveolar defects in rats and constitute a promising model for reconstruction of human maxillary alveolar defects in patients with cleft lip and palate. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Repairable chip bonding/interconnect process

DOEpatents

Bernhardt, Anthony F.; Contolini, Robert J.; Malba, Vincent; Riddle, Robert A.

1997-01-01

A repairable, chip-to-board interconnect process which addresses cost and testability issues in the multi-chip modules. This process can be carried out using a chip-on-sacrificial-substrate technique, involving laser processing. This process avoids the curing/solvent evolution problems encountered in prior approaches, as well is resolving prior plating problems and the requirements for fillets. For repairable high speed chip-to-board connection, transmission lines can be formed on the sides of the chip from chip bond pads, ending in a gull wing at the bottom of the chip for subsequent solder.

Reverse Transcription of a Self-Primed Retrotransposon Requires an RNA Structure Similar to the U5-IR Stem-Loop of Retroviruses

PubMed Central

Lin, Jia-Hwei; Levin, Henry L.

1998-01-01

An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV. The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop. Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of Tf1 does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak U5-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the U5-IR structure. However, all of the mutations in the U5-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5′ end of Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer. Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. PMID:9774699

Effect of autologous adipose-derived mesenchymal stem cell therapy in the treatment of a post-traumatic chondral defect of the knee

PubMed Central

Freitag, Julien; Li, Douglas; Wickham, James; Shah, Kiran; Tenen, Abi

2017-01-01

Isolated chondral defects have a limited capacity to heal and predispose to the development of osteoarthritis. Current surgical management can be unpredictable in outcome. Improved understanding of the action of mesenchymal stem cells (MSCs) has seen renewed interest in their role in cartilage repair. A 26-year-old athlete presented with a post-traumatic, isolated patella chondral defect. The patient underwent an arthroscopy with removal of a chondral loose body. After failure to symptomatically improve 12 months following surgery, the patient received intra-articular autologous adipose-derived mesenchymal stem cell (ADMSC) therapy. PMID:29038190

Human Urine-Derived Stem Cells: Potential for Cell-Based Therapy of Cartilage Defects

PubMed Central

Chen, Long; Li, Lang; Xing, Fei; Peng, Jing; Peng, Kun; Wang, Yuanzheng

2018-01-01

Stem cell therapy is considered an optimistic approach to replace current treatments for cartilage defects. Recently, human urine-derived stem cells (hUSCs), which are isolated from the urine, are studied as a promising candidate for many tissue engineering therapies due to their multipotency and sufficient proliferation activities. However, it has not yet been reported whether hUSCs can be employed in cartilage defects. In this study, we revealed that induced hUSCs expressed chondrogenic-related proteins, including aggrecan and collagen II, and their gene expression levels were upregulated in vitro. Moreover, we combined hUSCs with hyaluronic acid (HA) and injected hUSCs-HA into a rabbit knee joint with cartilage defect. Twelve weeks after the injection, the histologic analyses (HE, toluidine blue, and Masson trichrome staining), immunohistochemistry (aggrecan and collagen II), and histologic grade of the sample indicated that hUSCs-HA could stimulate much more neocartilage formation compared with hUSCs alone, pure HA, and saline, which only induced the modest cartilage regeneration. In this study, we demonstrated that hUSCs could be a potential cell source for stem cell therapies to treat cartilage-related defects in the future. PMID:29765413

Cost and utilization of above ground biomass in thinning systems

Treesearch

Billy Watson; Bryce Stokes

1994-01-01

The cost and utilization were compared for a thinning operation removing the stems as roundwood with a flail chipper operation. The flail chipper operation recovered an additional 4.2 tons of acceptable chips per acre which resulted in a higher return to the site. There was little difference in the cost of acceptable chips delivered to the digester between the two...

Therapeutic strategies involving uterine stem cells in reproductive medicine.

PubMed

Simoni, Michael; Taylor, Hugh S

2018-06-01

The current review provides an update on recent advances in stem cell biology relevant to female reproduction. Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction. A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.

Chip-based three-dimensional cell culture in perfused micro-bioreactors.

PubMed

Gottwald, Eric; Lahni, Brigitte; Thiele, David; Giselbrecht, Stefan; Welle, Alexander; Weibezahn, Karl-Friedrich

2008-05-21

We have developed a chip-based cell culture system for the three-dimensional cultivation of cells. The chip is typically manufactured from non-biodegradable polymers, e.g., polycarbonate or polymethyl methacrylate by micro injection molding, micro hot embossing or micro thermo-forming. But, it can also be manufactured from bio-degradable polymers. Its overall dimensions are 0.7 1 x 20 x 20 x 0.7 1 mm (h x w x l). The main features of the chips used are either a grid of up to 1156 cubic micro-containers (cf-chip) each the size of 120-300 x 300 x 300 micron (h x w x l) or round recesses with diameters of 300 micron and a depth of 300 micron (r-chip). The scaffold can house 10 Mio. cells in a three-dimensional configuration. For an optimal nutrient and gas supply, the chip is inserted in a bioreactor housing. The bioreactor is part of a closed sterile circulation loop that, in the simplest configuration, is additionally comprised of a roller pump and a medium reservoir with a gas supply. The bioreactor can be run in perfusion, superfusion, or even a mixed operation mode. We have successfully cultivated cell lines as well as primary cells over periods of several weeks. For rat primary liver cells we could show a preservation of organotypic functions for more than 2 weeks. For hepatocellular carcinoma cell lines we could show the induction of liver specific genes not or only slightly expressed in standard monolayer culture. The system might also be useful as a stem cell cultivation system since first differentiation experiments with stem cell lines were promising.

Research on defects inspection of solder balls based on eddy current pulsed thermography.

PubMed

Zhou, Xiuyun; Zhou, Jinlong; Tian, Guiyun; Wang, Yizhe

2015-10-13

In order to solve tiny defect detection for solder balls in high-density flip-chip, this paper proposed feasibility study on the effect of detectability as well as classification based on eddy current pulsed thermography (ECPT). Specifically, numerical analysis of 3D finite element inductive heat model is generated to investigate disturbance on the temperature field for different kind of defects such as cracks, voids, etc. The temperature variation between defective and non-defective solder balls is monitored for defects identification and classification. Finally, experimental study is carried on the diameter 1mm tiny solder balls by using ECPT and verify the efficacy of the technique.

Fabrication of polydimethylsiloxane (PDMS) nanofluidic chips with controllable channel size and spacing.

PubMed

Peng, Ran; Li, Dongqing

2016-10-07

The ability to create reproducible and inexpensive nanofluidic chips is essential to the fundamental research and applications of nanofluidics. This paper presents a novel and cost-effective method for fabricating a single nanochannel or multiple nanochannels in PDMS chips with controllable channel size and spacing. Single nanocracks or nanocrack arrays, positioned by artificial defects, are first generated on a polystyrene surface with controllable size and spacing by a solvent-induced method. Two sets of optimal working parameters are developed to replicate the nanocracks onto the polymer layers to form the nanochannel molds. The nanochannel molds are used to make the bi-layer PDMS microchannel-nanochannel chips by simple soft lithography. An alignment system is developed for bonding the nanofluidic chips under an optical microscope. Using this method, high quality PDMS nanofluidic chips with a single nanochannel or multiple nanochannels of sub-100 nm width and height and centimeter length can be obtained with high repeatability.

Development of non-destructive evaluation system using an HTS-SQUID gradiometer for magnetized materials

NASA Astrophysics Data System (ADS)

Kawano, J.; Tsukamoto, A.; Adachi, S.; Oshikubo, Y.; Hato, T.; Tanabe, K.; Okamura, T.

We have developed a new eddy-current non-destructive evaluation (NDE) system using an HTS SQUID gradiometer with the aim of applying it to practical materials with magnetization. The new NDE system employs a LN2-cooled external Cu pickup coil and an HTS SQUID chip placed in a magnetic shield made of HTS material. The HTS SQUID chip consists of an HTS planar gradiometer manufactured by using a ramp-edge junction technology and a multi-turn HTS thin film input coil coupled with the flip-chip configuration. The first-order coaxial gradiometric Cu pickup coil with a diameter of 16 mm and the baseline of 5.6 mm was used in the present NDE experiments. By using this NDE system, we could observe defect-induced magnetic signals without an appreciable influence of magnetization up to 10 mT. We also examined the ability of detecting deep-lying defects and compared with the results obtained using our previous NDE system.

PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects.

PubMed

Dashtdar, Havva; Murali, Malliga Raman; Abbas, Azlina Amir; Suhaeb, Abdulrazzaq Mahmod; Selvaratnam, Lakshmi; Tay, Liang Xin; Kamarul, Tunku

2015-05-01

To investigate whether mesenchymal stem cells (MSCs) seeded in novel polyvinyl alcohol (PVA)-chitosan composite hydrogel can provide comparable or even further improve cartilage repair outcomes as compared to previously established alginate-transplanted models. Medial femoral condyle defect was created in both knees of twenty-four mature New Zealand white rabbits, and the animals were divided into four groups containing six animals each. After 3 weeks, the right knees were transplanted with PVA-chitosan-MSC, PVA-chitosan scaffold alone, alginate-MSC construct or alginate alone. The left knee was kept as untreated control. Animals were killed at the end of 6 months after transplantation, and the cartilage repair was assessed through Brittberg morphological score, histological grading by O'Driscoll score and quantitative glycosaminoglycan analysis. Morphological and histological analyses showed significant (p < 0.05) tissue repair when treated with PVA-chitosan-MSC or alginate MSC as compared to the scaffold only and untreated control. In addition, safranin O staining and the glycosaminoglycan (GAG) content were significantly higher (p < 0.05) in MSC treatment groups than in scaffold-only or untreated control group. No significant difference was observed between the PVA-chitosan-MSC- and alginate-MSC-treated groups. PVA-chitosan hydrogel seeded with mesenchymal stem cells provides comparable treatment outcomes to that of previously established alginate-MSC construct implantation. This study supports the potential use of PVA-chitosan hydrogel seeded with MSCs for clinical use in cartilage repair such as traumatic injuries.

Analysis of DNA-chip and antigen-chip data: studies of cancer, stem cells and autoimmune diseases

NASA Astrophysics Data System (ADS)

Domany, Eytan

2005-07-01

Biology has undergone a revolution during the past decade. Deciphering the human genome has opened new horizons, among which the advent of DNA microarrays has been perhaps the most significant. These miniature measuring devices report the levels at which tens of thousands of genes are expressed in a collection of cells of interest (such as tissue from a tumor). I describe here briefly this technology and present an example of how analysis of data obtained from such high throughput experiments provides insights of possible clinical and therapeutic relevance for Acute Lymphoblastic Leukemia. Next, I describe how gene expression data is used to deduce a new design principle, " Just In Case", used by stem cells. Finally I briefly review a different novel technology, of antigen chips, which provide a fingerprint of a subject's immune system and may become a predictive clinical tool. The work reviewed here was done in collaboration with numerous colleagues and students.

Comparison of contamination of femoral heads and pre-processed bone chips during hip revision arthroplasty.

PubMed

Mathijssen, N M C; Sturm, P D; Pilot, P; Bloem, R M; Buma, P; Petit, P L; Schreurs, B W

2013-12-01

With bone impaction grafting, cancellous bone chips made from allograft femoral heads are impacted in a bone defect, which introduces an additional source of infection. The potential benefit of the use of pre-processed bone chips was investigated by comparing the bacterial contamination of bone chips prepared intraoperatively with the bacterial contamination of pre-processed bone chips at different stages in the surgical procedure. To investigate baseline contamination of the bone grafts, specimens were collected during 88 procedures before actual use or preparation of the bone chips: in 44 procedures intraoperatively prepared chips were used (Group A) and in the other 44 procedures pre-processed bone chips were used (Group B). In 64 of these procedures (32 using locally prepared bone chips and 32 using pre-processed bone chips) specimens were also collected later in the procedure to investigate contamination after use and preparation of the bone chips. In total, 8 procedures had one or more positive specimen(s) (12.5 %). Contamination rates were not significantly different between bone chips prepared at the operating theatre and pre-processed bone chips. In conclusion, there was no difference in bacterial contamination between bone chips prepared from whole femoral heads in the operating room and pre-processed bone chips, and therefore, both types of bone allografts are comparable with respect to risk of infection.

Repairable chip bonding/interconnect process

DOEpatents

Bernhardt, A.F.; Contolini, R.J.; Malba, V.; Riddle, R.A.

1997-08-05

A repairable, chip-to-board interconnect process which addresses cost and testability issues in the multi-chip modules is disclosed. This process can be carried out using a chip-on-sacrificial-substrate technique, involving laser processing. This process avoids the curing/solvent evolution problems encountered in prior approaches, as well is resolving prior plating problems and the requirements for fillets. For repairable high speed chip-to-board connection, transmission lines can be formed on the sides of the chip from chip bond pads, ending in a gull wing at the bottom of the chip for subsequent solder. 10 figs.

Autologous dental pulp stem cells in periodontal regeneration: a case report.

PubMed

Aimetti, Mario; Ferrarotti, Francesco; Cricenti, Luca; Mariani, Giulia Maria; Romano, Federica

2014-01-01

Histologic findings in animal models suggest that the application of dental pulp stem cells (DPSCs) may promote periodontal regeneration in infrabony defects. This case report describes the clinical and radiographic regenerative potential of autologous DPSCs in the treatment of human noncontained intraosseous defects. A chronic periodontitis patient with one vital third molar requiring extraction was surgically treated. The third molar was extracted and used as an autologous DPSCs source to regenerate the infrabony defect on the mandibular right second premolar. At the 1-year examination, the defect was completely filled with bonelike tissue as confirmed through the reentry procedure.

Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial.

PubMed

Bajestan, Mona N; Rajan, Archana; Edwards, Sean P; Aronovich, Sharon; Cevidanes, Lucia H S; Polymeri, Angeliki; Travan, Suncica; Kaigler, Darnell

2017-10-01

Stem cell therapy with bone marrow-derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone. To determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma. Eighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re-entered and the bone width re-assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading. The mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re-treated with autogenous block bone graft. The ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate. © 2017 Wiley Periodicals, Inc.

An automatic chip structure optical inspection system for electronic components

NASA Astrophysics Data System (ADS)

Song, Zhichao; Xue, Bindang; Liang, Jiyuan; Wang, Ke; Chen, Junzhang; Liu, Yunhe

2018-01-01

An automatic chip structure inspection system based on machine vision is presented to ensure the reliability of electronic components. It consists of four major modules, including a metallographic microscope, a Gigabit Ethernet high-resolution camera, a control system and a high performance computer. An auto-focusing technique is presented to solve the problem that the chip surface is not on the same focusing surface under the high magnification of the microscope. A panoramic high-resolution image stitching algorithm is adopted to deal with the contradiction between resolution and field of view, caused by different sizes of electronic components. In addition, we establish a database to storage and callback appropriate parameters to ensure the consistency of chip images of electronic components with the same model. We use image change detection technology to realize the detection of chip images of electronic components. The system can achieve high-resolution imaging for chips of electronic components with various sizes, and clearly imaging for the surface of chip with different horizontal and standardized imaging for ones with the same model, and can recognize chip defects.

Low-power, transparent optical network interface for high bandwidth off-chip interconnects.

PubMed

Liboiron-Ladouceur, Odile; Wang, Howard; Garg, Ajay S; Bergman, Keren

2009-04-13

The recent emergence of multicore architectures and chip multiprocessors (CMPs) has accelerated the bandwidth requirements in high-performance processors for both on-chip and off-chip interconnects. For next generation computing clusters, the delivery of scalable power efficient off-chip communications to each compute node has emerged as a key bottleneck to realizing the full computational performance of these systems. The power dissipation is dominated by the off-chip interface and the necessity to drive high-speed signals over long distances. We present a scalable photonic network interface approach that fully exploits the bandwidth capacity offered by optical interconnects while offering significant power savings over traditional E/O and O/E approaches. The power-efficient interface optically aggregates electronic serial data streams into a multiple WDM channel packet structure at time-of-flight latencies. We demonstrate a scalable optical network interface with 70% improvement in power efficiency for a complete end-to-end PCI Express data transfer.

An economic evaluation of a chlorhexidine chip for treating chronic periodontitis: the CHIP (chlorhexidine in periodontitis) study.

PubMed

Henke, C J; Villa, K F; Aichelmann-Reidy, M E; Armitage, G C; Eber, R M; Genco, R J; Killoy, W J; Miller, D P; Page, R C; Polson, A M; Ryder, M I; Silva, S J; Somerman, M J; Van Dyke, T E; Wolff, L F; Evans, C J; Finkelman, R D

2001-11-01

The authors previously suggested that an adjunctive, controlled-release chlorhexidine, or CHX, chip may reduce periodontal surgical needs at little additional cost. This article presents an economic analysis of the CHX chip in general dental practice. In a one-year prospective clinical trial, 484 chronic periodontitis patients in 52 general practices across the United States were treated with either scaling and root planing, or SRP, plus any therapy prescribed by treating, unblinded dentists; or SRP plus other therapy as above but including the CHX chip. Economic data were collected from bills, case report forms and 12-month treatment recommendations from blinded periodontist evaluators. Total dental charges were higher for SRP + CHX chip patients vs. SRP patients when CHX chip costs were included (P = .027) but lower when CHX chip costs were excluded (P = .012). About one-half of the CHX chip acquisition cost was offset by savings in other charges. SRP + CHX chip patients were about 50 percent less likely to undergo surgical procedures than were SRP patients (P = .021). At the end of the trial, periodontist evaluators recommended similar additional procedures for both groups: SRP, about 46 percent; maintenance, about 37 percent; surgery, 56 percent for SRP alone and 63 percent for SRP + CHX chip. Adjunctive CHX chip use for general-practice patients with periodontitis increased costs but reduced surgeries over one year. At study's end, periodontists recommended similar additional surgical treatment for both groups. In general practice, routine use of the CHX chip suggests that costs will be partially offset by reduced surgery over at least one year.

Reconstructed bone chip detachment is a risk factor for sinusitis after transsphenoidal surgery.

PubMed

Hsu, Yao-Wen; Ho, Ching-Yin; Yen, Yu-Shu

2014-01-01

Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. Prospective cohort study. We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July 2011. All patients were followed up with nasal endoscopy for at least 6 weeks. Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

PubMed

Nakajima, Kengo; Kunimatsu, Ryo; Ando, Kazuyo; Ando, Toshinori; Hayashi, Yoko; Kihara, Takuya; Hiraki, Tomoka; Tsuka, Yuji; Abe, Takaharu; Kaku, Masato; Nikawa, Hiroki; Takata, Takashi; Tanne, Kazuo; Tanimoto, Kotaro

2018-03-11

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip.

PubMed

Torisawa, Yu-Suke; Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Mammoto, Akiko; Watters, Alexander L; Bahinski, Anthony; Ingber, Donald E

2016-05-01

Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro.

Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature.

PubMed

Morad, Golnaz; Kheiri, Lida; Khojasteh, Arash

2013-12-01

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration. An electronic search of English-language papers was conducted on PubMed database. Studies that assessed the use of DPSCs in bone regeneration in vivo were included and experiments evaluating regeneration of hard tissues other than bone were excluded. The retrieved articles were thoroughly reviewed according to the source of stem cell, cell carrier, the in vivo experimental model, defect type, method of evaluating bone regeneration, and the obtained results. Further assessment of the results was conducted by classifying the studies based on the defect type. Seventeen papers formed the basis of this systematic review. Sixteen out of 17 experiments were performed on animal models with mouse and rat being the most frequently used animal models. Seven out of 17 animal studies, contained subcutaneous pockets on back of the animal for stem cell implantation. In only one study hard tissue formation was not observed. Other types of defects used in the retrieved studies, included cranial defects and mandibular bone defects, in all of which bone formation was reported. When applied in actual bone defects, DPSCs were capable of regenerating bone. Nevertheless, a precise conclusion regarding the efficiency of DPSCs for bone regeneration is yet to be made, considering the limited number of the in vivo experiments and the heterogeneity within their methods. Copyright © 2013 Elsevier Ltd. All rights reserved.

Performance of defect-tolerant set-associative cache memories

NASA Technical Reports Server (NTRS)

Frenzel, J. F.

1991-01-01

The increased use of on-chip cache memories has led researchers to investigate their performance in the presence of manufacturing defects. Several techniques for yield improvement are discussed and results are presented which indicate that set-associativity may be used to provide defect tolerance as well as improve the cache performance. Tradeoffs between several cache organizations and replacement strategies are investigated and it is shown that token-based replacement may be a suitable alternative to the widely-used LRU strategy.

Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells.

PubMed

Lee, Han M; Zhang, Hui; Schulz, Vincent; Tuck, David P; Forget, Bernard G

2010-08-05

Enforced expression of the homeobox transcription factor HOXB4 has been shown to enhance hematopoietic stem cell self-renewal and expansion ex vivo and in vivo. To investigate the downstream targets of HOXB4 in hematopoietic progenitor cells, HOXB4 was constitutively overexpressed in the primitive hematopoietic progenitor cell line EML. Two genome-wide analytical techniques were used: RNA expression profiling using microarrays and chromatin immunoprecipitation (ChIP)-chip. RNA expression profiling revealed that 465 gene transcripts were differentially expressed in KLS (c-Kit(+), Lin(-), Sca-1(+))-EML cells that overexpressed HOXB4 (KLS-EML-HOXB4) compared with control KLS-EML cells that were transduced with vector alone. In particular, erythroid-specific gene transcripts were observed to be highly down-regulated in KLS-EML-HOXB4 cells. ChIP-chip analysis revealed that the promoter region for 1910 genes, such as CD34, Sox4, and B220, were occupied by HOXB4 in KLS-EML-HOXB4 cells. Side-by-side comparison of the ChIP-chip and RNA expression profiling datasets provided correlative information and identified Gp49a and Laptm4b as candidate "stemness-related" genes. Both genes were highly ranked in both dataset lists and have been previously shown to be preferentially expressed in hematopoietic stem cells and down-regulated in mature hematopoietic cells, thus making them attractive candidates for future functional studies in hematopoietic cells.

Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration.

PubMed

Leucht, Philipp; Kim, Jae-Beom; Amasha, Raimy; James, Aaron W; Girod, Sabine; Helms, Jill A

2008-09-01

The fetal skeleton arises from neural crest and from mesoderm. Here, we provide evidence that each lineage contributes a unique stem cell population to the regeneration of injured adult bones. Using Wnt1Cre::Z/EG mice we found that the neural crest-derived mandible heals with neural crest-derived skeletal stem cells, whereas the mesoderm-derived tibia heals with mesoderm-derived stem cells. We tested whether skeletal stem cells from each lineage were functionally interchangeable by grafting mesoderm-derived cells into mandibular defects, and vice versa. All of the grafting scenarios, except one, healed through the direct differentiation of skeletal stem cells into osteoblasts; when mesoderm-derived cells were transplanted into tibial defects they differentiated into osteoblasts but when transplanted into mandibular defects they differentiated into chondrocytes. A mismatch between the Hox gene expression status of the host and donor cells might be responsible for this aberration in bone repair. We found that initially, mandibular skeletal progenitor cells are Hox-negative but that they adopt a Hoxa11-positive profile when transplanted into a tibial defect. Conversely, tibial skeletal progenitor cells are Hox-positive and maintain this Hox status even when transplanted into a Hox-negative mandibular defect. Skeletal progenitor cells from the two lineages also show differences in osteogenic potential and proliferation, which translate into more robust in vivo bone regeneration by neural crest-derived cells. Thus, embryonic origin and Hox gene expression status distinguish neural crest-derived from mesoderm-derived skeletal progenitor cells, and both characteristics influence the process of adult bone regeneration.

Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

PubMed

Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

2018-04-11

Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

Hybridization-based biosensor containing hairpin probes and use thereof

DOEpatents

Miller, Benjamin L.; Strohsahl, Christopher M.

2010-10-12

A sensor chip that includes: a fluorescence quenching surface; a nucleic acid probe that contains first and second ends with the first end bound to the fluorescence quenching surface, and is characterized by being able to self-anneal into a hairpin conformation; and a first fluorophore bound to the second end of the first nucleic acid molecule. When the first nucleic acid molecule is in the hairpin conformation, the fluorescence quenching surface substantially quenches fluorescent emissions by the first fluorophore; and when the first nucleic acid molecule is in a non-hairpin conformation, fluorescent emissions by the fluorophore are substantially free of quenching by the fluorescence quenching surface. Various nucleic acid probes, methods of making the sensor chip, biological sensor devices that contain the sensor chip, and their methods of use are also disclosed.

Single event effects on the APV25 front-end chip

NASA Astrophysics Data System (ADS)

Friedl, M.; Bauer, T.; Pernicka, M.

2003-03-01

The Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider at CERN will include a Silicon Strip Tracker covering a sensitive area of 206 m2. About ten million channels will be read out by APV25 front-end chips, fabricated in the 0.25 μm deep submicron process. Although permanent damage is not expected within CMS radiation levels, transient Single Event Upsets are inevitable. Moreover, localized ionization can also produce fake signals in the analog circuitry. Eight APV25 chips were exposed to a high-intensity pion beam at the Paul Scherrer Institute (Villigen/CH) to study the radiation induced effects in detail. The results, which are compatible to similar measurements performed with heavy ions, are used to predict the chip error rate at CMS.

Chip morphology as a performance predictor during high speed end milling of soda lime glass

NASA Astrophysics Data System (ADS)

Bagum, M. N.; Konneh, M.; Abdullah, K. A.; Ali, M. Y.

2018-01-01

Soda lime glass has application in DNA arrays and lab on chip manufacturing. Although investigation revealed that machining of such brittle material is possible using ductile mode under controlled cutting parameters and tool geometry, it remains a challenging task. Furthermore, ability of ductile machining is usually assed through machined surface texture examination. Soda lime glass is a strain rate and temperature sensitive material. Hence, influence on attainment of ductile surface due to adiabatic heat generated during high speed end milling using uncoated tungsten carbide tool is investigated in this research. Experimental runs were designed using central composite design (CCD), taking spindle speed, feed rate and depth of cut as input variable and tool-chip contact point temperature (Ttc) and the surface roughness (Rt) as responses. Along with machined surface texture, Rt and chip morphology was examined to assess machinability of soda lime glass. The relation between Ttc and chip morphology was examined. Investigation showed that around glass transition temperature (Tg) ductile chip produced and subsequently clean and ductile final machined surface produced.

Fanca−/− hematopoietic stem cells demonstrate a mobilization defect which can be overcome by administration of the Rac inhibitor NSC23766

PubMed Central

Milsom, Michael D.; Lee, Andrew W.; Zheng, Yi; Cancelas, Jose A.

2009-01-01

Fanconi anemia is a severe bone marrow failure syndrome resulting from inactivating mutations of Fanconi anemia pathway genes. Gene and cell therapy trials using hematopoietic stem cells and progenitors have been hampered by poor mobilization of HSC to peripheral blood in response to G-CSF. Using a murine model of Fanconi anemia (Fanca−/− mice), we found that the Fanca deficiency was associated with a profound defect in hematopoietic stem cells and progenitors mobilization in response to G-CSF in absence of bone marrow failure, which correlates with the findings of clinical trials in Fanconi anemia patients. This mobilization defect was overcome by co-administration of the Rac inhibitor NSC23766, suggesting that Rac signaling is implicated in the retention of Fanca−/− hematopoietic stem cells and progenitors in the bone marrow. In view of these data, we propose that targeting Rac signaling may enhance G-CSF-induced HSC mobilization in Fanconi anemia. PMID:19491337

Fanca-/- hematopoietic stem cells demonstrate a mobilization defect which can be overcome by administration of the Rac inhibitor NSC23766.

PubMed

Milsom, Michael D; Lee, Andrew W; Zheng, Yi; Cancelas, Jose A

2009-07-01

Fanconi anemia is a severe bone marrow failure syndrome resulting from inactivating mutations of Fanconi anemia pathway genes. Gene and cell therapy trials using hematopoietic stem cells and progenitors have been hampered by poor mobilization of HSC to peripheral blood in response to G-CSF. Using a murine model of Fanconi anemia (Fanca(-/-) mice), we found that the Fanca deficiency was associated with a profound defect in hematopoietic stem cells and progenitors mobilization in response to G-CSF in absence of bone marrow failure, which correlates with the findings of clinical trials in Fanconi anemia patients. This mobilization defect was overcome by co-administration of the Rac inhibitor NSC23766, suggesting that Rac signaling is implicated in the retention of Fanca(-/-) hematopoietic stem cells and progenitors in the bone marrow. In view of these data, we propose that targeting Rac signaling may enhance G-CSF-induced HSC mobilization in Fanconi anemia.

Absolute dose calibration of an X-ray system and dead time investigations of photon-counting techniques

NASA Astrophysics Data System (ADS)

Carpentieri, C.; Schwarz, C.; Ludwig, J.; Ashfaq, A.; Fiederle, M.

2002-07-01

High precision concerning the dose calibration of X-ray sources is required when counting and integrating methods are compared. The dose calibration for a dental X-ray tube was executed with special dose calibration equipment (dosimeter) as function of exposure time and rate. Results were compared with a benchmark spectrum and agree within ±1.5%. Dead time investigations with the Medipix1 photon-counting chip (PCC) have been performed by rate variations. Two different types of dead time, paralysable and non-paralysable will be discussed. The dead time depends on settings of the front-end electronics and is a function of signal height, which might lead to systematic defects of systems. Dead time losses in excess of 30% have been found for the PCC at 200 kHz absorbed photons per pixel.

Translational Research: Palatal-derived Ecto-mesenchymal Stem Cells from Human Palate: A New Hope for Alveolar Bone and Cranio-Facial Bone Reconstruction

PubMed Central

Grimm, Wolf Dieter; Dannan, Aous; Giesenhagen, Bernd; Schau, Ingmar; Varga, Gabor; Vukovic, Mark Alexander; Sirak, Sergey Vladimirovich

2014-01-01

The management of facial defects has rapidly changed in the last decade. Functional and esthetic requirements have steadily increased along with the refinements of surgery. In the case of advanced atrophy or jaw defects, extensive horizontal and vertical bone augmentation is often unavoidable to enable patients to be fitted with implants. Loss of vertical alveolar bone height is the most common cause for a non primary stability of dental implants in adults. At present, there is no ideal therapeutic approach to cure loss of vertical alveolar bone height and achieve optimal pre-implantological bone regeneration before dental implant placement. Recently, it has been found that specific populations of stem cells and/or progenitor cells could be isolated from different dental resources, namely the dental follicle, the dental pulp and the periodontal ligament. Our research group has cultured palatal-derived stem cells (paldSCs) as dentospheres and further differentiated into various cells of the neuronal and osteogenic lineage, thereby demonstrating their stem cell state. In this publication will be shown whether paldSCs could be differentiated into the osteogenic lineage and, if so, whether these cells are able to regenerate alveolar bone tissue in vivo in an athymic rat model. Furthermore, using these data we have started a proof of principle clinical- and histological controlled study using stem cell-rich palatal tissues for improving the vertical alveolar bone augmentation in critical size defects. The initial results of the study demonstrate the feasibility of using stem cell-mediated tissue engineering to treat alveolar bone defects in humans. PMID:24921024

Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone.

PubMed

Zellner, Johannes; Hierl, Katja; Mueller, Michael; Pfeifer, Christian; Berner, Arne; Dienstknecht, Thomas; Krutsch, Werner; Geis, Sebastian; Gehmert, Sebastian; Kujat, Richard; Dendorfer, Sebastian; Prantl, Lukas; Nerlich, Michael; Angele, Peter

2013-10-01

Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5-0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

On-chip photonic-phononic emitter-receiver apparatus

DOEpatents

Cox, Jonathan Albert; Jarecki, Jr., Robert L.; Rakich, Peter Thomas; Wang, Zheng; Shin, Heedeuk; Siddiqui, Aleem; Starbuck, Andrew Lea

2017-07-04

A radio-frequency photonic devices employs photon-phonon coupling for information transfer. The device includes a membrane in which a two-dimensionally periodic phononic crystal (PnC) structure is patterned. The device also includes at least a first optical waveguide embedded in the membrane. At least a first line-defect region interrupts the PnC structure. The first optical waveguide is embedded within the line-defect region.

Stem-quality changes on young, mixed upland hardwoods after crop-tree release

Treesearch

David L. Sonderman; David L. Sonderman

1987-01-01

Relative change of several types of stem defects was studied over an 8-year period to determine the effects of crop-tree thinning on the development of tree quality. Special interest was given to changes in relative quality associated with defect indicators of crop trees compared to trees in unthinned plots. The relative quality classes of the crop trees went from...

TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

PubMed

Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

2014-12-01

Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.

Frequency Control of Single Quantum Emitters in Integrated Photonic Circuits

NASA Astrophysics Data System (ADS)

Schmidgall, Emma R.; Chakravarthi, Srivatsa; Gould, Michael; Christen, Ian R.; Hestroffer, Karine; Hatami, Fariba; Fu, Kai-Mei C.

2018-02-01

Generating entangled graph states of qubits requires high entanglement rates, with efficient detection of multiple indistinguishable photons from separate qubits. Integrating defect-based qubits into photonic devices results in an enhanced photon collection efficiency, however, typically at the cost of a reduced defect emission energy homogeneity. Here, we demonstrate that the reduction in defect homogeneity in an integrated device can be partially offset by electric field tuning. Using photonic device-coupled implanted nitrogen vacancy (NV) centers in a GaP-on-diamond platform, we demonstrate large field-dependent tuning ranges and partial stabilization of defect emission energies. These results address some of the challenges of chip-scale entanglement generation.

Frequency Control of Single Quantum Emitters in Integrated Photonic Circuits.

PubMed

Schmidgall, Emma R; Chakravarthi, Srivatsa; Gould, Michael; Christen, Ian R; Hestroffer, Karine; Hatami, Fariba; Fu, Kai-Mei C

2018-02-14

Generating entangled graph states of qubits requires high entanglement rates with efficient detection of multiple indistinguishable photons from separate qubits. Integrating defect-based qubits into photonic devices results in an enhanced photon collection efficiency, however, typically at the cost of a reduced defect emission energy homogeneity. Here, we demonstrate that the reduction in defect homogeneity in an integrated device can be partially offset by electric field tuning. Using photonic device-coupled implanted nitrogen vacancy (NV) centers in a GaP-on-diamond platform, we demonstrate large field-dependent tuning ranges and partial stabilization of defect emission energies. These results address some of the challenges of chip-scale entanglement generation.

Product assurance technology for procuring reliable, radiation-hard, custom LSI/VLSI electronics

NASA Technical Reports Server (NTRS)

Buehler, M. G.; Allen, R. A.; Blaes, B. R.; Hicks, K. A.; Jennings, G. A.; Lin, Y.-S.; Pina, C. A.; Sayah, H. R.; Zamani, N.

1989-01-01

Advanced measurement methods using microelectronic test chips are described. These chips are intended to be used in acquiring the data needed to qualify Application Specific Integrated Circuits (ASIC's) for space use. Efforts were focused on developing the technology for obtaining custom IC's from CMOS/bulk silicon foundries. A series of test chips were developed: a parametric test strip, a fault chip, a set of reliability chips, and the CRRES (Combined Release and Radiation Effects Satellite) chip, a test circuit for monitoring space radiation effects. The technical accomplishments of the effort include: (1) development of a fault chip that contains a set of test structures used to evaluate the density of various process-induced defects; (2) development of new test structures and testing techniques for measuring gate-oxide capacitance, gate-overlap capacitance, and propagation delay; (3) development of a set of reliability chips that are used to evaluate failure mechanisms in CMOS/bulk: interconnect and contact electromigration and time-dependent dielectric breakdown; (4) development of MOSFET parameter extraction procedures for evaluating subthreshold characteristics; (5) evaluation of test chips and test strips on the second CRRES wafer run; (6) two dedicated fabrication runs for the CRRES chip flight parts; and (7) publication of two papers: one on the split-cross bridge resistor and another on asymmetrical SRAM (static random access memory) cells for single-event upset analysis.

A front end readout electronics ASIC chip for position sensitive solid state detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kravis, S.D.; Tuemer, T.O.; Visser, G.J.

1998-12-31

A mixed signal Application Specific Integrated Circuit (ASIC) chip for front end readout electronics of position sensitive solid state detectors has been manufactured. It is called RENA (Readout Electronics for Nuclear Applications). This chip can be used for both medical and industrial imaging of X-rays and gamma rays. The RENA chip is a monolithic integrated circuit and has 32 channels with low noise high input impedance charge sensitive amplifiers. It works in pulse counting mode with good energy resolution. It also has a self triggering output which is essential for nuclear applications when the incident radiation arrives at random. Different,more » externally selectable, operational modes that includes a sparse readout mode is available to increase data throughput. It also has externally selectable shaping (peaking) times.« less

Back-end and interface implementation of the STS-XYTER2 prototype ASIC for the CBM experiment

NASA Astrophysics Data System (ADS)

Kasinski, K.; Szczygiel, R.; Zabolotny, W.

2016-11-01

Each front-end readout ASIC for the High-Energy Physics experiments requires robust and effective hit data streaming and control mechanism. A new STS-XYTER2 full-size prototype chip for the Silicon Tracking System and Muon Chamber detectors in the Compressed Baryonic Matter experiment at Facility for Antiproton and Ion Research (FAIR, Germany) is a 128-channel time and amplitude measuring solution for silicon microstrip and gas detectors. It operates at 250 kHit/s/channel hit rate, each hit producing 27 bits of information (5-bit amplitude, 14-bit timestamp, position and diagnostics data). The chip back-end implements fast front-end channel read-out, timestamp-wise hit sorting, and data streaming via a scalable interface implementing the dedicated protocol (STS-HCTSP) for chip control and hit transfer with data bandwidth from 9.7 MHit/s up to 47 MHit/s. It also includes multiple options for link diagnostics, failure detection, and throttling features. The back-end is designed to operate with the data acquisition architecture based on the CERN GBTx transceivers. This paper presents the details of the back-end and interface design and its implementation in the UMC 180 nm CMOS process.

Quality response of even-aged 80-year-old white oak trees after thinning

Treesearch

David L. Sonderman

1984-01-01

Stem defects were studied over an 18-year period to determine the effect of thinning intensity on quality development of 80-year-old white oak trees. Seventy-nine white oak trees from a thinning study in Kentucky were analyzed from stereo photographs taken in 1960 and 1978. Stem-related defects were measured on the butt 8-foot and second 8-foot sections of each tree....

Effect of thinning on growth and potential quality of young white oak crop trees

Treesearch

Martin E. Dale; David L. Sonderman

1984-01-01

Relative change in several types of stem defects were studied over a 16-year period to determine the effect of thinning intensity on the development of tree quality. We studied quality changes on sample white oak crop trees that were selected from five density levels created in a 1961 thinning. Branch-related and other stem defects on the butt 16-foot section were...

Stand density-a factor affecting stem quality of young hardwoods

Treesearch

David L. Sonderman; David L. Sonderman

1985-01-01

A 14-year-old mixed oak stand was thinned in 1977 to stocking levels of 30, 50, and 60 percent and a control. From this stand, 117 trees were selected and their stem-related defects recorded. Six years later these same trees were reevaluated. The number of limb defects per square foot of surface area increased substantially more in the heavily thinned plots than in the...

ITO/gold nanoparticle/RGD peptide composites to enhance electrochemical signals and proliferation of human neural stem cells.

PubMed

Kim, Tae-Hyung; El-Said, Waleed Ahmed; An, Jeung Hee; Choi, Jeong-Woo

2013-04-01

A cell chip composed of ITO, gold nanoparticles (GNP) and RGD-MAP-C peptide composites was fabricated to enhance the electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The structural characteristics of the fabricated surfaces were confirmed by both scanning electron microscopy and surface-enhanced Raman spectroscopy. HB1.F3 cells were allowed to attach to various composites electrodes in the cell chip and the material-dependent effects on electrochemical signals and cell proliferation were analyzed. The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to be the best material in regards to enhancing the voltammetric signals of HB1.F3 cells when exposed to cyclic voltammetry, as well as for increasing cell proliferation. Differential pulse voltammetry was performed to evaluate the adverse effects of doxorubicin on HB1.F3 cells. In these experiments, negative correlations between cell viability and chemical concentrations were obseved, which were more sensitive than MTT viability assay especially at low concentrations (<0.1 μg/mL). In this basic science study, a cell chip composed of ITO, gold nanoparticles and RGD-MAP-C peptide composites was fabricated to enhance electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to best enhance the voltammetric signals of the studied cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Seamless Combination of Fluorescence-Activated Cell Sorting and Hanging-Drop Networks for Individual Handling and Culturing of Stem Cells and Microtissue Spheroids.

PubMed

Birchler, Axel; Berger, Mischa; Jäggin, Verena; Lopes, Telma; Etzrodt, Martin; Misun, Patrick Mark; Pena-Francesch, Maria; Schroeder, Timm; Hierlemann, Andreas; Frey, Olivier

2016-01-19

Open microfluidic cell culturing devices offer new possibilities to simplify loading, culturing, and harvesting of individual cells or microtissues due to the fact that liquids and cells/microtissues are directly accessible. We present a complete workflow for microfluidic handling and culturing of individual cells and microtissue spheroids, which is based on the hanging-drop network concept: The open microfluidic devices are seamlessly combined with fluorescence-activated cell sorting (FACS), so that individual cells, including stem cells, can be directly sorted into specified culturing compartments in a fully automated way and at high accuracy. Moreover, already assembled microtissue spheroids can be loaded into the microfluidic structures by using a conventional pipet. Cell and microtissue culturing is then performed in hanging drops under controlled perfusion. On-chip drop size control measures were applied to stabilize the system. Cells and microtissue spheroids can be retrieved from the chip by using a parallelized transfer method. The presented methodology holds great promise for combinatorial screening of stem-cell and multicellular-spheroid cultures.

Semiconductor chips, genes, and stem cells: new wine for new bottles?

PubMed

Rose, Simone A

2012-01-01

This Article analogizes early semiconductor technology and its surrounding economics with isolated genes, stem cells, and related bioproducts, and their surrounding economics, to make the case for sui generis (of its own class) intellectual property protection for isolated bioproducts. Just as early semiconductors failed to meet the patent social bargain requiring novelty and non-obviousness in the 1980s, isolated genes and stem cells currently fail to meet the patent bargain requirements of non-obviousness and eligible subject matter that entitle them to traditional intellectual property protection. Like early semiconductor chip designs, nevertheless, the high cost of upstream bioproduct research and development, coupled with the need to sustain continued economic growth of the biotechnology industry, mandates that Congress provide some level of exclusive rights to ensure continued funding for this research. Sui generis intellectual property protection for isolated bioproducts would preserve the incentive to continue innovation in the field. As illustrated by the semiconductor industry, however, such sui generis protection for this technology must include limitations that address the need to provide an appropriate level of public access to facilitate downstream product development and enrich the public domain.

Fast-growing willow shrub named `Fish Creek`

DOEpatents

Abrahamson, Lawrence P.; Kopp, Richard F.; Smart, Lawrence B.; Volk, Timothy A.

2007-05-08

A distinct male cultivar of Salix purpurea named `Fish Creek`, characterized by rapid stem growth producing greater than 30% more woody biomass than either of its parents (`94001` and `94006`) and 20% more biomass than a current production cultivar (`SV1`). `Fish Creek` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Fish Creek` displays a low incidence of rust disease or damage by beetles or sawflies.

Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold.

PubMed

Liu, Zeping; Yin, Xing; Ye, Qingsong; He, Wulin; Ge, Mengke; Zhou, Xiaofu; Hu, Jing; Zou, Shujuan

2016-07-01

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagen-hydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells - collagen-hydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 ± 20 µm and 203 ± 18 µm and porosity of 69 ± 0.5% and 50 ± 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells - collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells - collagen-hydroxyapatite and collagen-hydroxyapatite scaffold - induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation. © The Author(s) 2016.

Surface morphology and dislocation characteristics near the surface of 4H-SiC wafer using multi-directional scanning transmission electron microscopy.

PubMed

Sato, Takahiro; Orai, Yoshihisa; Suzuki, Yuya; Ito, Hiroyuki; Isshiki, Toshiyuki; Fukui, Munetoshi; Nakamura, Kuniyasu; Schamp, C T

2017-10-01

To improve the reliability of silicon carbide (SiC) electronic power devices, the characteristics of various kinds of crystal defects should be precisely understood. Of particular importance is understanding the correlation between the surface morphology and the near surface dislocations. In order to analyze the dislocations near the surface of 4H-SiC wafers, a dislocation analysis protocol has been developed. This protocol consists of the following process: (1) inspection of surface defects using low energy scanning electron microscopy (LESEM), (2) identification of small and shallow etch pits using KOH low temperature etching, (3) classification of etch pits using LESEM, (4) specimen preparation of several hundred nanometer thick sample using the in-situ focused ion beam micro-sampling® technique, (5) crystallographic analysis using the selected diffraction mode of the scanning transmission electron microscope (STEM), and (6) determination of the Burgers vector using multi-directional STEM (MD-STEM). The results show a correlation between the triangular terrace shaped surface defects and an hexagonal etch pit arising from threading dislocations, linear shaped surface defects and elliptical shaped etch pits arising from basal plane dislocations. Through the observation of the sample from two orthogonal directions via the MD-STEM technique, a basal plane dislocation is found to dissociate into an extended dislocation bound by two partial dislocations. A protocol developed and presented in this paper enables one to correlate near surface defects of a 4H-SiC wafer with the root cause dislocations giving rise to those surface defects. © The Author 2017. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CHIP protects against cardiac pressure overload through regulation of AMPK

PubMed Central

Schisler, Jonathan C.; Rubel, Carrie E.; Zhang, Chunlian; Lockyer, Pamela; Cyr, Douglas M.; Patterson, Cam

2013-01-01

Protein quality control and metabolic homeostasis are integral to maintaining cardiac function during stress; however, little is known about if or how these systems interact. Here we demonstrate that C terminus of HSC70-interacting protein (CHIP), a regulator of protein quality control, influences the metabolic response to pressure overload by direct regulation of the catalytic α subunit of AMPK. Induction of cardiac pressure overload in Chip–/– mice resulted in robust hypertrophy and decreased cardiac function and energy generation stemming from a failure to activate AMPK. Mechanistically, CHIP promoted LKB1-mediated phosphorylation of AMPK, increased the specific activity of AMPK, and was necessary and sufficient for stress-dependent activation of AMPK. CHIP-dependent effects on AMPK activity were accompanied by conformational changes specific to the α subunit, both in vitro and in vivo, identifying AMPK as the first physiological substrate for CHIP chaperone activity and establishing a link between cardiac proteolytic and metabolic pathways. PMID:23863712

The use of low resistivity substrates for optimal noise reduction, ground referencing, and current conduction in mixed signal ASICs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zimmerman, T.

1997-12-01

This paper is distilled from a talk given at the 3rd International Meeting on Front End Electronics in Taos, N.M. on Nov. 7,1997. It is based on experience gained by designing and testing the SVX3 128 channel silicon strip detector readout chip. The SVX3 chip organization is shown in Fig. 1. The Front End section consists of an integrator and analog pipeline designed at Fermilab, and the Back End section is an ADC plus sparsification and readout logic designed at LBL. SVX3 is a deadtimeless readout chip, which means that the front end is acquiring low level analog signals whilemore » the back end is digitizing and reading out digital signals. It is thus a true mixed signal chip, and demands close attention to avoid disastrous coupling from the digital to the analog sections. SVX3 is designed in a bulk CMOS process (i.e., the circuits sit in a silicon substrate). In such a process, the substrate becomes a potential coupling path. This paper discusses the effect of the substrate resistivity on coupling, and also goes into a more general discussion of grounding and referencing in mixed signal designs and how low resistivity substrates can be used to advantage. Finally, an alternative power supply current conduction method for ASICs is presented as an additional advantage which can be obtained with low resistivity substrates. 1 ref., 13 figs., 1 tab.« less

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Beigbeder, C.; Bernier, R.; Breton, D.; Bonneaud, G.; Caceres, T.; Chase, R.; Chauveau, J.; Del Buono, L.; Dohou, F.; Ducorps, A.; Gastaldi, F.; Genat, J. F.; Hrisoho, A.; Imbert, P.; Lebbolo, H.; Matricon, P.; Oxoby, G.; Renard, C.; Roos, L.; Sen, S.; Thiebaux, C.; Truong, K.; Tocut, V.; Vasileiadis, G.; Va'Vra, J.; Verderi, M.; Warner, D.; Wilson, R. J.; Wormser, G.; Zhang, B.; Zomer, F.

2000-12-01

Recent results from the Front-End electronics of the Detector of Internally Reflected Cerenkov light (DIRC) for the BaBar experiment at SLAC (Stanford, USA) are presented. It measures to better than 1 ns the arrival time of Cerenkov photoelectrons detected in a 11000 phototubes array and their amplitude spectra. It mainly comprises 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom digital time to digital chips (TDC) for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected front up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test results of the pre-production chips are presented, as well as system tests.

In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects

PubMed Central

Jiang, Tongmeng; Xu, Guojie; Wang, Qiuyan; Yang, Lihui; Zheng, Li; Zhao, Jinmin; Zhang, Xingdong

2017-01-01

In vitro cultured autologous mesenchymal stem cells (MSCs) within passage 5 have been approved for clinical application in stem cell-based treatment of cartilage defects. However, their chondrogenic potential has not yet been questioned or verified. In this study, the chondrogenic potential of bone marrow MSCs at passage 3 (P3 BMSCs) was investigated both in cartilage repair and in vitro, with freshly isolated bone marrow mononuclear cells (BMMNCs) as controls. The results showed that P3 BMSCs were inferior to BMMNCs not only in their chondrogenic differentiation ability but also as candidates for long-term repair of cartilage defects. Compared with BMMNCs, P3 BMSCs presented a decay in telomerase activity and a change in chromosomal morphology with potential anomalous karyotypes, indicating senescence. In addition, interindividual variability in P3 BMSCs is much higher than in BMMNCs, demonstrating genomic instability. Interestingly, remarkable downregulation in cell cycle, DNA replication and mismatch repair (MMR) pathways as well as in multiple genes associated with telomerase activity and chromosomal stability were found in P3 BMSCs. This result indicates that telomerase and chromosome anomalies might originate from expansion, leading to impaired stemness and pluripotency of stem cells. In vitro culture and expansion are not recommended for cell-based therapy, and fresh BMMNCs are the first choice. PMID:28569773

Vacuolar invertase gene silencing in potato (Solanum tuberosum L.) improves processing quality by decreasing the frequency of sugar-end defects

USDA-ARS?s Scientific Manuscript database

Sugar-end defect is a tuber quality disorder that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form da...

Language Classification using N-grams Accelerated by FPGA-based Bloom Filters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, A; Gokhale, M

N-Gram (n-character sequences in text documents) counting is a well-established technique used in classifying the language of text in a document. In this paper, n-gram processing is accelerated through the use of reconfigurable hardware on the XtremeData XD1000 system. Our design employs parallelism at multiple levels, with parallel Bloom Filters accessing on-chip RAM, parallel language classifiers, and parallel document processing. In contrast to another hardware implementation (HAIL algorithm) that uses off-chip SRAM for lookup, our highly scalable implementation uses only on-chip memory blocks. Our implementation of end-to-end language classification runs at 85x comparable software and 1.45x the competing hardware design.

Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

PubMed

Kaseb, Hatem O; Lewis, Dale W; Saunders, William S; Gollin, Susanne M

2016-09-01

Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex.

PubMed

Wachi, Tomoka; Cornell, Brett; Marshall, Courtney; Zhukarev, Vladimir; Baas, Peter W; Toyo-oka, Kazuhito

2016-06-01

14-3-3 proteins are ubiquitously-expressed and multifunctional proteins. There are seven isoforms in mammals with a high level of homology, suggesting potential functional redundancy. We previously found that two of seven isoforms, 14-3-3epsilon and 14-3-3zeta, are important for brain development, in particular, radial migration of pyramidal neurons in the developing cerebral cortex. In this work, we analyzed the function of another isoform, the protein 14-3-3gamma, with respect to neuronal migration in the developing cortex. We found that in utero 14-3-3gamma-deficiency resulted in delays in neuronal migration as well as morphological defects. Migrating neurons deficient in 14-3-3gamma displayed a thicker leading process stem, and the basal ends of neurons were not able to reach the boundary between the cortical plate and the marginal zone. Consistent with the results obtained from in utero electroporation, time-lapse live imaging of brain slices revealed that the ablation of the 14-3-3gamma proteins in pyramidal neurons slowed down their migration. In addition, the 14-3-3gamma deficient neurons showed morphological abnormalities, including increased multipolar neurons with a thicker leading processes stem during migration. These results indicate that the 14-3-3gamma proteins play an important role in radial migration by regulating the morphology of migrating neurons in the cerebral cortex. The findings underscore the pathological phenotypes of brain development associated with the disruption of different 14-3-3 proteins and will advance the preclinical data regarding disorders caused by neuronal migration defects. © 2015 Wiley Periodicals, Inc.

A new press-fit stem concept to reduce the risk of end-of-stem pain at revision TKA: a pre-clinical study.

PubMed

Completo, A; Fonseca, F; Simões, J A; Ramos, A; Relvas, C

2012-10-01

Revision total knee arthroplasty presents numerous technical challenges, with lower patient outcomes compared with those obtained in primary surgery. Extended stems have been used in revision total knee arthroplasty to improve component alignment and fixation. Hybrid fixation with cemented tibial tray and press-fit stem has shown good results. One of the disadvantages of this technique is pain related to the presence of a cementless diaphyseal engaging stem, often designated as end-of-stem pain. Patients with this pain have reported a decrease in overall satisfaction, as well as demonstrate a lower clinical outcome score. Clinical findings suggest that stem material and design are important factors in the development of end-of-stem pain. Therefore, a question can be raised: can a novel press-fit stem concept minimize bone strain changes at the stem tip? The hypothesis here considered lies upon the fact, that if periosteal cortex strain changes are minimized at the stem tip comparatively to the intact situation, the risk of end-of-stem pain might be minimized. This pre-clinical study was accomplished using synthetic tibiae to experimentally predict the periosteal cortex strains at the proximal and stem tip regions, with a commercial press-fit stem and a new stem concept. The results demonstrated that the new stem concept has the ability to minimize strain changes induced by the stem tip at the distal periosteal cortex and consequently, at the periosteal layer of bone tissue, which is highly pain sensitive, probably contributing to the reduction of the risk of end-of-stem pain. Copyright © 2012 Elsevier B.V. All rights reserved.

7 CFR 51.1911 - Damaged.

Code of Federal Regulations, 2012 CFR

2012-01-01

... stem to the blossom end. (c) Catfaces. These are irregular, dark, leathery scars at the blossom end of...) Growth cracks. These are ruptures or cracks radiating from the stem scar, or concentric to the stem scar... margin of the stem scar; except that very narrow, well healed cracks concentric to the stem scar shall...

7 CFR 51.1911 - Damaged.

Code of Federal Regulations, 2011 CFR

2011-01-01

... stem to the blossom end. (c) Catfaces. These are irregular, dark, leathery scars at the blossom end of...) Growth cracks. These are ruptures or cracks radiating from the stem scar, or concentric to the stem scar... margin of the stem scar; except that very narrow, well healed cracks concentric to the stem scar shall...

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

PubMed

Janner, Simone F M; Bosshardt, Dieter D; Cochran, David L; Chappuis, Vivianne; Huynh-Ba, Guy; Jones, Archie A; Buser, Daniel

2017-11-01

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5 weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM + membrane (group D + M), autogenous bone chips + DBBM + membrane (group A + D + M), DBBM alone (group D) or autogenous bone chips + DBBM (group A + D). Four animals were sacrificed after 3 weeks of healing and four animals after 12 weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P < 0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12 weeks of healing (P < 0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P < 0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

PubMed Central

Doulatov, Sergei; Vo, Linda T.; Macari, Elizabeth R.; Wahlster, Lara; Kinney, Melissa A.; Taylor, Alison M.; Barragan, Jessica; Gupta, Manav; McGrath, Katherine; Lee, Hsiang-Ying; Humphries, Jessica M.; DeVine, Alex; Narla, Anupama; Alter, Blanche P.; Beggs, Alan H.; Agarwal, Suneet; Ebert, Benjamin L.; Gazda, Hanna T.; Lodish, Harvey F.; Sieff, Colin A.; Schlaeger, Thorsten M.; Zon, Leonard I.; Daley, George Q.

2017-01-01

Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA. PMID:28179501

Spontaneous emergence of overgrown molar teeth in a colony of Prairie voles (Microtus ochrogaster)

PubMed Central

Jheon, Andrew H; Prochazkova, Michaela; Sherman, Michael; Manoli, Devanand S; Shah, Nirao M; Carbone, Lawrence; Klein, Ophir

2015-01-01

Continuously growing incisors are common to all rodents, which include the Microtus genus of voles. However, unlike many rodents, voles also possess continuously growing molars. Here, we report spontaneous molar defects in a population of Prairie voles (Microtus ochrogaster). We identified bilateral protuberances on the ventral surface of the mandible in several voles in our colony. In some cases, the protuberances broke through the cortical bone. The mandibular molars became exposed and infected, and the maxillary molars entered the cranial vault. Visualisation upon soft tissue removal and microcomputed tomography (microCT) analyses confirmed that the protuberances were caused by the overgrowth of the apical ends of the molar teeth. We speculate that the unrestricted growth of the molars was due to the misregulation of the molar dental stem cell niche. Further study of this molar phenotype may yield additional insight into stem cell regulation and the evolution and development of continuously growing teeth. PMID:25634121

The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells.

PubMed

Xu, Bowen; Cai, Ling; Butler, Jason M; Chen, Dongliang; Lu, Xiongdong; Allison, David F; Lu, Rui; Rafii, Shahin; Parker, Joel S; Zheng, Deyou; Wang, Gang Greg

2018-03-13

Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC "stemness" genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of "stemness" gene-expression programs and proper function of adult HSCs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Detection of small-size solder ball defects through heat conduction analysis

NASA Astrophysics Data System (ADS)

Zhou, Xiuyun; Chen, Yaqiu; Lu, Xiaochuan

2018-02-01

Aiming to solve the defect detection problem of a small-size solder ball in the high density chip, heat conduction analysis based on eddy current pulsed thermography is put forward to differentiate various defects. With establishing the 3D finite element model about induction heating, defects such as cracks and void can be distinguished by temperature difference resulting from heat conduction. Furthermore, the experiment of 0.4 mm-diameter solder balls with different defects is carried out to prove that crack and void solder can be distinguished. Three kinds of crack length on a gull-wing pin are selected, including 0.24 mm, 1.2 mm, and 2.16 mm, to verify that the small defect can be discriminated. Both the simulation study and experiment result show that the heat conduction analysis method is reliable and convenient.

Fast-growing shrub willow named `Owasco`

DOEpatents

Abrahamson, Lawrence P.; Kopp, Richard F.; Smart, Lawrence B.; Volk, Timothy A.

2007-07-03

A distinct female cultivar of Salix viminalis.times.Salix miyabeana named `Owasco`, characterized by rapid stem growth producing greater than 49% more woody biomass than one of its parents (`SX64`) and 39% more biomass than a current production cultivar (`SV1`). `Otisco` produced greater than 2.7-fold more stem biomass than two other current production cultivars, `SX67` and `SX61`. `Owasco` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Owasco` displays a low incidence of rust disease and is not damaged by potato leafhoppers.

Fast-growing willow shrub named `Millbrook`

DOEpatents

Abrahamson, Lawrence P [Marcellus, NY; Kopp, Richard F [Marietta, NY; Smart, Lawrence B [Geneva, NY; Volk, Timothy A [Syracuse, NY

2007-04-24

A distinct female cultivar of Salix purpurea.times.Salix miyabeana named `Millbrook`, characterized by rapid stem growth producing 9% more woody biomass than one of its parents (`SX64`) and 2% more biomass than a current production cultivar (`SV1`). `Millbrook` produced greater than 2-fold more stem biomass than two other current production cultivars, `SX67` and `SX61`. `Millbrook` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Millbrook` displays a low incidence of rust disease.

Fast-growing willow shrub named `Otisco`

DOEpatents

Abrahamson, Lawrence P.; Kopp, Richard F.; Smart, Lawrence B.; Volk, Timothy A.

2007-09-11

A distinct female cultivar of Salix viminalis.times.S. miyabeana named `Otisco`, characterized by rapid stem growth producing greater than 42% more woody biomass than one of its parents (`SX64`) and 33% more biomass than a current production cultivar (`SV1`). `Otisco` produced greater than 2.5-fold more stem biomass than two other current production cultivars, `SX67` and `SX61`. `Otisco` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Otisco` displays a low incidence of rust disease and is not damaged by potato leafhoppers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrahamson, Lawrence P; Kopp, Richard F; Smart, Lawrence B

A distinct female cultivar of Salix viminalis.times.S. miyabeana named `Otisco`, characterized by rapid stem growth producing greater than 42% more woody biomass than one of its parents (`SX64`) and 33% more biomass than a current production cultivar (`SV1`). `Otisco` produced greater than 2.5-fold more stem biomass than two other current production cultivars, `SX67` and `SX61`. `Otisco` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after twomore » to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Otisco` displays a low incidence of rust disease and is not damaged by potato leafhoppers.« less

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

PubMed

Hu, Bin; Li, Yan; Wang, Mohan; Zhu, Youming; Zhou, Yong; Sui, Baiyan; Tan, Yu; Ning, Yujie; Wang, Jie; He, Jiacai; Yang, Chi; Zou, Duohong

2018-06-10

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-L-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/β-tricalcium phosphate (β-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/β-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/β-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fast-growing willow shrub named `Fish Creek`

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrahamson, Lawrence P; Kopp, Richard F; Smart, Lawrence B

2007-05-08

A distinct male cultivar of Salix purpurea named `Fish Creek`, characterized by rapid stem growth producing greater than 30% more woody biomass than either of its parents (`94001` and `94006`) and 20% more biomass than a current production cultivar (`SV1`). `Fish Creek` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. Themore » stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Fish Creek` displays a low incidence of rust disease or damage by beetles or sawflies.« less

Fast-growing willow shrub named `Oneida`

DOEpatents

Abrahamson, Lawrence P [Marcellus, NY; Kopp, Richard F [Marietta, NY; Smart, Lawrence B [Geneva, NY; Volk, Timothy A [Syracuse, NY

2007-05-01

A distinct male cultivar of Salix purpurea.times.S. miyabeana named `Oneida`, characterized by rapid stem growth producing 2.7-times greater woody biomass than one of its parents (`SX67`) and greater than 36% more biomass than current production cultivars (`SV1` and `SX64`). `Oneida` can be planted from dormant stem cuttings, produces multiple stems after coppice, and the stem biomass can be harvested when the plant is dormant. In the spring following harvest, the plant will re-sprout very vigorously, producing new stems that can be harvested after two to four years of growth. This harvest cycle can be repeated several times. The stem biomass can be chipped and burned as a source of renewable energy, generating heat and/or electricity. `Oneida` displays a low incidence of rust disease or damage by beetles or sawflies.

Carboxyl Terminus of HSC70-interacting Protein (CHIP) Down-regulates NF-κB-inducing Kinase (NIK) and Suppresses NIK-induced Liver Injury*

PubMed Central

Jiang, Bijie; Shen, Hong; Chen, Zheng; Yin, Lei; Zan, Linsen; Rui, Liangyou

2015-01-01

Ser/Thr kinase NIK (NF-κB-inducing kinase) mediates the activation of the noncanonical NF-κB2 pathway, and it plays an important role in regulating immune cell development and liver homeostasis. NIK levels are extremely low in quiescent cells due to ubiquitin/proteasome-mediated degradation, and cytokines stimulate NIK activation through increasing NIK stability; however, regulation of NIK stability is not fully understood. Here we identified CHIP (carboxyl terminus of HSC70-interacting protein) as a new negative regulator of NIK. CHIP contains three N-terminal tetratricopeptide repeats (TPRs), a middle dimerization domain, and a C-terminal U-box. The U-box domain contains ubiquitin E3 ligase activity that promotes ubiquitination of CHIP-bound partners. We observed that CHIP bound to NIK via its TPR domain. In both HEK293 and primary hepatocytes, overexpression of CHIP markedly decreased NIK levels at least in part through increasing ubiquitination and degradation of NIK. Accordingly, CHIP suppressed NIK-induced activation of the noncanonical NF-κB2 pathway. CHIP also bound to TRAF3, and CHIP and TRAF3 acted coordinately to efficiently promote NIK degradation. The TPR but not the U-box domain was required for CHIP to promote NIK degradation. In mice, hepatocyte-specific overexpression of NIK resulted in liver inflammation and injury, leading to death, and liver-specific expression of CHIP reversed the detrimental effects of hepatic NIK. Our data suggest that CHIP/TRAF3/NIK interactions recruit NIK to E3 ligase complexes for ubiquitination and degradation, thus maintaining NIK at low levels. Defects in CHIP regulation of NIK may result in aberrant NIK activation in the liver, contributing to live injury, inflammation, and disease. PMID:25792747

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome

PubMed Central

Layman, W.S.; McEwen, D.P.; Beyer, L.A.; Lalani, S.R.; Fernbach, S.D.; Oh, E.; Swaroop, A.; Hegg, C.C.; Raphael, Y.; Martens, J.R.; Martin, D.M.

2009-01-01

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7Gt/+ olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development. PMID:19279158

Single-Chip CMUT-on-CMOS Front-End System for Real-Time Volumetric IVUS and ICE Imaging

PubMed Central

Gurun, Gokce; Tekes, Coskun; Zahorian, Jaime; Xu, Toby; Satir, Sarp; Karaman, Mustafa; Hasler, Jennifer; Degertekin, F. Levent

2014-01-01

Intravascular ultrasound (IVUS) and intracardiac echography (ICE) catheters with real-time volumetric ultrasound imaging capability can provide unique benefits to many interventional procedures used in the diagnosis and treatment of coronary and structural heart diseases. Integration of CMUT arrays with front-end electronics in single-chip configuration allows for implementation of such catheter probes with reduced interconnect complexity, miniaturization, and high mechanical flexibility. We implemented a single-chip forward-looking (FL) ultrasound imaging system by fabricating a 1.4-mm-diameter dual-ring CMUT array using CMUT-on-CMOS technology on a front-end IC implemented in 0.35-µm CMOS process. The dual-ring array has 56 transmit elements and 48 receive elements on two separate concentric annular rings. The IC incorporates a 25-V pulser for each transmitter and a low-noise capacitive transimpedance amplifier (TIA) for each receiver, along with digital control and smart power management. The final shape of the silicon chip is a 1.5-mm-diameter donut with a 430-µm center hole for a guide wire. The overall front-end system requires only 13 external connections and provides 4 parallel RF outputs while consuming an average power of 20 mW. We measured RF A-scans from the integrated single-chip array which show full functionality at 20.1 MHz with 43% fractional bandwidth. We also tested and demonstrated the image quality of the system on a wire phantom and an ex-vivo chicken heart sample. The measured axial and lateral point resolutions are 92 µm and 251 µm, respectively. We successfully acquired volumetric imaging data from the ex-vivo chicken heart with 60 frames per second without any signal averaging. These demonstrative results indicate that single-chip CMUT-on-CMOS systems have the potential to produce real-time volumetric images with image quality and speed suitable for catheter based clinical applications. PMID:24474131

Single-chip CMUT-on-CMOS front-end system for real-time volumetric IVUS and ICE imaging.

PubMed

Gurun, Gokce; Tekes, Coskun; Zahorian, Jaime; Xu, Toby; Satir, Sarp; Karaman, Mustafa; Hasler, Jennifer; Degertekin, F Levent

2014-02-01

Intravascular ultrasound (IVUS) and intracardiac echography (ICE) catheters with real-time volumetric ultrasound imaging capability can provide unique benefits to many interventional procedures used in the diagnosis and treatment of coronary and structural heart diseases. Integration of capacitive micromachined ultrasonic transducer (CMUT) arrays with front-end electronics in single-chip configuration allows for implementation of such catheter probes with reduced interconnect complexity, miniaturization, and high mechanical flexibility. We implemented a single-chip forward-looking (FL) ultrasound imaging system by fabricating a 1.4-mm-diameter dual-ring CMUT array using CMUT-on-CMOS technology on a front-end IC implemented in 0.35-μm CMOS process. The dual-ring array has 56 transmit elements and 48 receive elements on two separate concentric annular rings. The IC incorporates a 25-V pulser for each transmitter and a low-noise capacitive transimpedance amplifier (TIA) for each receiver, along with digital control and smart power management. The final shape of the silicon chip is a 1.5-mm-diameter donut with a 430-μm center hole for a guide wire. The overall front-end system requires only 13 external connections and provides 4 parallel RF outputs while consuming an average power of 20 mW. We measured RF A-scans from the integrated single- chip array which show full functionality at 20.1 MHz with 43% fractional bandwidth. We also tested and demonstrated the image quality of the system on a wire phantom and an ex vivo chicken heart sample. The measured axial and lateral point resolutions are 92 μm and 251 μm, respectively. We successfully acquired volumetric imaging data from the ex vivo chicken heart at 60 frames per second without any signal averaging. These demonstrative results indicate that single-chip CMUT-on-CMOS systems have the potential to produce realtime volumetric images with image quality and speed suitable for catheter-based clinical applications.

A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation.

PubMed

Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chih-Chen; Yet, Shaw-Fang; Hsu, Chia-Hsien

2016-07-06

The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

Epigenetic modulation by TFII-I during embryonic stem cell differentiation.

PubMed

Bayarsaihan, Dashzeveg; Makeyev, Aleksandr V; Enkhmandakh, Badam

2012-10-01

TFII-I transcription factors play an essential role during early vertebrate embryogenesis. Genome-wide mapping studies by ChIP-seq and ChIP-chip revealed that TFII-I primes multiple genomic loci in mouse embryonic stem cells and embryonic tissues. Moreover, many TFII-I-bound regions co-localize with H3K4me3/K27me3 bivalent chromatin within the promoters of lineage-specific genes. This minireview provides a summary of current knowledge regarding the function of TFII-I in epigenetic control of stem cell differentiation. Copyright © 2012 Wiley Periodicals, Inc.

AE (Acoustic Emission) for Flip-Chip CGA/FCBGA Defect Detection

NASA Technical Reports Server (NTRS)

Ghaffarian, Reza

2014-01-01

C-mode scanning acoustic microscopy (C-SAM) is a nondestructive inspection technique that uses ultrasound to show the internal feature of a specimen. A very high or ultra-high-frequency ultrasound passes through a specimen to produce a visible acoustic microimage (AMI) of its inner features. As ultrasound travels into a specimen, the wave is absorbed, scattered or reflected. The response is highly sensitive to the elastic properties of the materials and is especially sensitive to air gaps. This specific characteristic makes AMI the preferred method for finding "air gaps" such as delamination, cracks, voids, and porosity. C-SAM analysis, which is a type of AMI, was widely used in the past for evaluation of plastic microelectronic circuits, especially for detecting delamination of direct die bonding. With the introduction of the flip-chip die attachment in a package; its use has been expanded to nondestructive characterization of the flip-chip solder bumps and underfill. Figure 1.1 compares visual and C-SAM inspection approaches for defect detection, especially for solder joint interconnections and hidden defects. C-SAM is specifically useful for package features like internal cracks and delamination. C-SAM not only allows for the visualization of the interior features, it has the ability to produce images on layer-by-layer basis. Visual inspection; however, is only superior to C-SAM for the exposed features including solder dewetting, microcracks, and contamination. Ideally, a combination of various inspection techniques - visual, optical and SEM microscopy, C-SAM, and X-ray - need to be performed in order to assure quality at part, package, and system levels. This reports presents evaluations performed on various advanced packages/assemblies, especially the flip-chip die version of ball grid array/column grid array (BGA/CGA) using C-SAM equipment. Both external and internal equipment was used for evaluation. The outside facility provided images of the key features that could be detected using the most advanced C-SAM equipment with a skilled operator. Investigation continued using in-house equipment with its limitations. For comparison, representative X-rays of the assemblies were also gathered to show key defect detection features of these non-destructive techniques. Key images gathered and compared are: Compared the images of 2D X-ray and C-SAM for a plastic LGA assembly showing features that could be detected by either NDE technique. For this specific case, X-ray was a clear winner. Evaluated flip-chip CGA and FCBGA assemblies with and without heat sink by C-SAM. Only the FCCGA package that had no heat sink could be fully analyzed for underfill and bump quality. Cross-sectional microscopy did not revealed peripheral delamination features detected by C-SAM. Analyzed a number of fine pitch PBGA assemblies by C-SAM. Even though the internal features of the package assemblies could be detected, C-SAM was unable to detect solder joint failure at either the package or board level. Twenty times touch ups by solder iron with 700degF tip temperature, each with about 5 second duration, did not induce defects to be detected by C-SAM images. Other techniques need to be considered to induce known defects for characterization. Given NASA's emphasis on the use of microelectronic packages and assemblies and quality assurance on workmanship defect detection, understanding key features of various inspection systems that detect defects in the early stages of package and assembly is critical to developing approaches that will minimize future failures. Additional specific, tailored non-destructive inspection approaches could enable low-risk insertion of these advanced electronic packages having hidden and fine features.

Repair of Osteochondral Defects Using Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model

PubMed Central

Jia, Yanhui; Yuan, Mei; Guo, Weimin; Huang, Jingxiang; Zhao, Bin; Xu, Wenjing; Lu, Shibi

2017-01-01

Umbilical cord Wharton's jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor-β-induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications. PMID:28261617

Vacuolar invertase gene silencing in potato decreasing the frequency of sugar-end defects

USDA-ARS?s Scientific Manuscript database

Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one e...

Translational Applications of Tissue Engineering in Cardiovascular Medicine.

PubMed

Dogan, Arin; Elcin, A Eser; Elcin, Y Murat

2017-03-26

Cardiovascular diseases are the leading cause of global deaths. The current paradigm in medicine seeks novel approaches for the treatment of progressive or end-stage diseases. The organ transplantation option is limited in availability, and unfortunately, a significant number of patients are lost while waiting for donor organs. Animal studies have shown that upon myocardial infarction, it is possible to stop adverse remodeling in its tracks and reverse with tissue engineering methods. Regaining the myocardium function and avoiding further deterioration towards heart failure can benefit millions of people with a significantly lesser burden on healthcare systems worldwide. The advent of induced pluripotent stem cells brings the unique advantage of testing candidate drug molecules on organ-on-chip systems, which mimics human heart in vitro. Biomimetic three-dimensional constructs that contain disease-specific or normal cardiomyocytes derived from human induced pluripotent stem cells are a useful tool for screening drug molecules and studying dosage, mode of action and cardio-toxicity. Tissue engineering approach aims to develop the treatments for heart valve deficiency, ischemic heart disease and a wide range of vascular diseases. Translational research seeks to improve the patient's quality of life, progressing towards developing cures, rather than treatments. To this end, researchers are working on tissue engineered heart valves, blood vessels, cardiac patches, and injectable biomaterials, hence developing new ways for engineering bio-artificial organs or tissue parts that the body will adopt as its own. In this review, we summarize translational methods for cardiovascular tissue engineering and present useful tables on pre-clinical and clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimal fluorescence waveband determination for detecting defect cherry tomatoes using fluorescence excitation-emission matrix

USDA-ARS?s Scientific Manuscript database

A multi-spectral fluorescence imaging technique was used to detect defect cherry tomatoes. The fluorescence excitation and emission matrix was used to measure for defects, sound surface, and stem areas to determine the optimal fluorescence excitation and emission wavelengths for discrimination. Two-...

Optimization of Thermal Preprocessing for Efficient Combustion of Woody Biomass

NASA Astrophysics Data System (ADS)

Kumagai, Seiji; Aranai, Masahiko; Takeda, Koichi; Enda, Yukio

We attempted to optimize both drying time and temperature for stem chips and bark of Japanese cedar in order to obtain the largest release of combustion heat. Moisture release rates of the stem and bark during air-drying in an oven were evaluated. Higher and lower heating values of stem and bark, dried at different temperatures for different lengths of time, were also evaluated. The drying conditions of 180°C and 30min resulted in the largest heat release of the stem (˜ 4%increase compared to conditions of 105°C and 30min). The optimal drying conditions were not obvious for bark. However, for the drying process in actual plants, the conditions of 180°C and 30min were suggested to be acceptable for both stem and bark.

A graphical automated detection system to locate hardwood log surface defects using high-resolution three-dimensional laser scan data

Treesearch

Liya Thomas; R. Edward Thomas

2011-01-01

We have developed an automated defect detection system and a state-of-the-art Graphic User Interface (GUI) for hardwood logs. The algorithm identifies defects at least 0.5 inch high and at least 3 inches in diameter on barked hardwood log and stem surfaces. To summarize defect features and to build a knowledge base, hundreds of defects were measured, photographed, and...

Experiences in flip chip production of radiation detectors

NASA Astrophysics Data System (ADS)

Savolainen-Pulli, Satu; Salonen, Jaakko; Salmi, Jorma; Vähänen, Sami

2006-09-01

Modern imaging devices often require heterogeneous integration of different materials and technologies. Because of yield considerations, material availability, and various technological limitations, an extremely fine pitch is necessary to realize high-resolution images. Thus, there is a need for a hybridization technology that is able to join together readout amplifiers and pixel detectors at a very fine pitch. This paper describes radiation detector flip chip production at VTT. Our flip chip technology utilizes 25-μm diameter tin-lead solder bumps at a 50-μm pitch and is based on flux-free bonding. When preprocessed wafers are used, as is the case here, the total yield is defined only partly by the flip chip process. Wafer preprocessing done by a third-party silicon foundry and the flip chip process create different process defects. Wafer-level yield maps (based on probing) provided by the customer are used to select good readout chips for assembly. Wafer probing is often done outside of a real clean room environment, resulting in particle contamination and/or scratches on the wafers. Factors affecting the total yield of flip chip bonded detectors are discussed, and some yield numbers of the process are given. Ways to improve yield are considered, and finally guidelines for process planning and device design with respect to yield optimization are given.

Application of Stem Cells in Oral Disease Therapy: Progresses and Perspectives

PubMed Central

Yang, Bo; Qiu, Yi; Zhou, Niu; Ouyang, Hong; Ding, Junjun; Cheng, Bin; Sun, Jianbo

2017-01-01

Stem cells are undifferentiated and pluripotent cells that can differentiate into specialized cells with a more specific function. Stem cell therapies become preferred methods for the treatment of multiple diseases. Oral and maxillofacial defect is one kind of the diseases that could be most possibly cured by stem cell therapies. Here we discussed oral diseases, oral adult stem cells, iPS cells, and the progresses/challenges/perspectives of application of stem cells for oral disease treatment. PMID:28421002

Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips

PubMed Central

Jung, Woo-Chul; Heo, Young-Moo; Yoon, Gil-Sang; Shin, Kwang-Ho; Chang, Sung-Ho; Kim, Gun-Hee; Cho, Myeong-Woo

2007-01-01

Recently, the polymeric micro-fluidic biochip, often called LOC (lab-on-a-chip), has been focused as a cheap, rapid and simplified method to replace the existing biochemical laboratory works. It becomes possible to form miniaturized lab functionalities on a chip with the development of MEMS technologies. The micro-fluidic chips contain many micro-channels for the flow of sample and reagents, mixing, and detection tasks. Typical substrate materials for the chip are glass and polymers. Typical techniques for microfluidic chip fabrication are utilizing various micro pattern forming methods, such as wet-etching, micro-contact printing, and hot-embossing, micro injection molding, LIGA, and micro powder blasting processes, etc. In this study, to establish the basis of the micro pattern fabrication and mass production of polymeric micro-fluidic chips using injection molding process, micro machining method was applied to form micro-channels on the LOC molds. In the research, a series of machining experiments using micro end-mills were performed to determine optimum machining conditions to improve surface roughness and shape accuracy of designed simplified micro-channels. Obtained conditions were used to machine required mold inserts for micro-channels using micro end-mills. Test injection processes using machined molds and COC polymer were performed, and then the results were investigated.

[Reconstruction of tangential and circular infected bone defects].

PubMed

Schmidt, H G; Neikes, M; Zimmer, W

1987-12-01

In the treatment of bone infections the reconstruction and rehabilitation of bone defects is a problem that often requires treatment secondary to curative treatment of the infection. For the reconstruction of smaller and more extensive defects we used predominantly (92.7%) autogenous (autologous) untreated spongiosa and in only 7% of the cases allogenic (homologous) spongiosa from an organ bank, this being added if necessary. Recently the additionally introduced vascularized bone chip has become a useful extension of the therapy concept. The problems and complications of defect reconstruction are demonstrated for 705 cases of bone infection with 472 defects of different sizes, based on a comprehensive classification with defect calculation. Surgical technical approach and special aspects of after-treatment are described, as well as the results for every group of cases. We achieved stability and freedom from infection in a total of 93.7% of the patients. As was to be expected, the problems grow with the size of the defect. Particularly problematic are joint infections with adjacent extensive circular defect.

Adipose-derived stem cells for cartilage regeneration - moving towards clinical applicability

PubMed Central

2013-01-01

Despite multiple methods of treatment and a wealth of research in the field of regenerative medicine focusing on cartilage defects, the management of cartilage injuries remains a challenge. A recent study by Van Pham and colleagues proposes a method for preconditioning autologous adipose-derived stem cells. Their study offers evidence about the increased proliferative and chondrogenetic capabilities of platelet-rich plasma-treated adipose-derived stem cells and the increased efficiency of these in treating articular cartilage defects in mice. Even though the method needs further elaboration and the composition of the repair tissue requires investigation, the results are promising for the design of clinically acceptable cell therapies aimed at cartilage regeneration. PMID:24079605

Repair of Spontaneous Cerebrospinal Fluid Otorrhea from Defect of Middle Cranial Fossa

PubMed Central

Goh, Young Bum; Han, Chi-Sung

2013-01-01

Spontaneous cerebrospinal fluid (CSF) otorrhea is defined as CSF otorrhea where there are no identifiable causes including previous trauma, surgery, infection, neoplasm or congenital anomaly. The condition is rare. The origin of CSF leak is commonly a defect in the tegmen of the middle cranial fossa. The pathophysiology of spontaneous CSF otorrhea is unclear. Two theories of the etiology of bony defects of the temporal bone are the congenital bony defect theory and arachnoid granulation theory. The authors experienced a case of a 49-year-old female patient admitted with the complaint of persistent right ear fullness. Computed tomography revealed a large defect of the middle fossa and suspicious CSF otorrhea through the defect of tegmen tympani. Repair was successful with multiple bone chips using the transmastoid approach. The postoperative course was good and there has been no recurrence of the CSF leakage. PMID:24653924

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2015-10-01

mesenchymal stem cells (MSCs). The in- flammatory... mesenchymal stem cells and the wound healing process. Cells 2013;2:621-34. 17. Kumar A, Salimath BP, Stark GB, Finkenzeller G. 22 K.M. Davis et al.: Muscle...Gao X, Usas A, Tang Y, et al. A comparison of bone re- generation with human mesenchymal stem cells and mus- cle-derived stem cells and the

Automatic thermographic image defect detection of composites

NASA Astrophysics Data System (ADS)

Luo, Bin; Liebenberg, Bjorn; Raymont, Jeff; Santospirito, SP

2011-05-01

Detecting defects, and especially reliably measuring defect sizes, are critical objectives in automatic NDT defect detection applications. In this work, the Sentence software is proposed for the analysis of pulsed thermography and near IR images of composite materials. Furthermore, the Sentence software delivers an end-to-end, user friendly platform for engineers to perform complete manual inspections, as well as tools that allow senior engineers to develop inspection templates and profiles, reducing the requisite thermographic skill level of the operating engineer. Finally, the Sentence software can also offer complete independence of operator decisions by the fully automated "Beep on Defect" detection functionality. The end-to-end automatic inspection system includes sub-systems for defining a panel profile, generating an inspection plan, controlling a robot-arm and capturing thermographic images to detect defects. A statistical model has been built to analyze the entire image, evaluate grey-scale ranges, import sentencing criteria and automatically detect impact damage defects. A full width half maximum algorithm has been used to quantify the flaw sizes. The identified defects are imported into the sentencing engine which then sentences (automatically compares analysis results against acceptance criteria) the inspection by comparing the most significant defect or group of defects against the inspection standards.

Potato Types and Characteristics: Laboratory Exercises.

ERIC Educational Resources Information Center

Pavlista, Alexander D.

1997-01-01

Presents a number of simple exercises that demonstrate potato tuber characteristics and are designed for high school biology students and teachers. Exercises include Typing, Grading, Shape, Eye Characteristics, Defects, Specific Gravity, Dry Matter Content, Glucose Content, Baking, Frying/Chipping, and Taste Testing. (JRH)

7 CFR 51.2655 - Damage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... defects shall be considered as damage: (a) Cracks within the stem cavity when deep or not well healed, or... healed crack one-sixteenth inch in width extending one-half the greatest circumference of the stem cavity; (b) Cracks outside of the stem cavity when deep or not well healed, or when the crack has weakened...

7 CFR 51.2655 - Damage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... defects shall be considered as damage: (a) Cracks within the stem cavity when deep or not well healed, or... healed crack one-sixteenth inch in width extending one-half the greatest circumference of the stem cavity; (b) Cracks outside of the stem cavity when deep or not well healed, or when the crack has weakened...

Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

PubMed

Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

2013-05-01

Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

Identification of the Cause of the Stem Neck Fracture in the Hip Joint Endoprosthesis

NASA Astrophysics Data System (ADS)

Ryniewicz, A. M.; Bojko, Ł.; Ryniewicz, A.; Pałka, P.; Ryniewicz, W.

2018-02-01

Endoprosthesis stem fractures are among the rarest complications that occur after hip joint arthroplasty. The aim of this paper is to evaluate the causes of the fractures of the Aura II stem neck, which is an element of an endoprosthesis implanted in a patient. In order to achieve it, a radiogram was evaluated, the FEM analysis was carried out for the hip joint replaced using the Aura II prosthesis and scanning tests as well as a chemical analysis were performed for the focus of fatigue. The tests performed indicate that the most probable causes leading to the fatigue fracture of the Aura II stem under examination were material defects in the process of casting and forging (forging the material with delamination and the presence of brittle oxides and carbides) that resulted in a significant reduction of strength and resistance to corrosion. In the light of an unprecedented stem neck fracture, this information should be an indication for non-destructive tests of ready-made stems aiming to discover the material and technological defects that may arise in the process of casting and drop forging.

On-chip Magnetic Separation and Cell Encapsulation in Droplets

NASA Astrophysics Data System (ADS)

Chen, A.; Byvank, T.; Bharde, A.; Miller, B. L.; Chalmers, J. J.; Sooryakumar, R.; Chang, W.-J.; Bashir, R.

2012-02-01

The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment could prevent cross-contamination, provide high recovery yield and ability to study biological traits at a single cell level These advantages of on-chip biological experiments contrast to conventional methods, which require bulk samples that provide only averaged information on cell metabolism. We report on a device that integrates microfluidic technology with a magnetic tweezers array to combine the functionality of separation and encapsulation of objects such as immunomagnetically labeled cells or magnetic beads into pico-liter droplets on the same chip. The ability to control the separation throughput that is independent of the hydrodynamic droplet generation rate allows the encapsulation efficiency to be optimized. The device can potentially be integrated with on-chip labeling and/or bio-detection to become a powerful single-cell analysis device.

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

PubMed

Thangarajah, Tanujan; Shahbazi, Shirin; Pendegrass, Catherine J; Lambert, Simon; Alexander, Susan; Blunn, Gordon W

2016-01-01

Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

Defective Hematopoietic Stem Cell and Lymphoid Progenitor Development in the Ts65Dn Mouse Model of Down Syndrome: Potential Role of Oxidative Stress

PubMed Central

Lorenzo, Laureanne Pilar E.; Chen, Haiyan; Shatynski, Kristen E.; Clark, Sarah; Yuan, Rong; Harrison, David E.; Yarowsky, Paul J.

2011-01-01

Abstract Aims Down Syndrome (DS), a genetic disease caused by a triplication of chromosome 21, is characterized by increased markers of oxidative stress. In addition to cognitive defects, patients with DS also display hematologic disorders and increased incidence of infections and leukemia. Using the Ts65Dn mouse model of DS, the goal of this study was to examine hematopoietic stem and lymphoid progenitor cell function in DS. Results Analysis of hematopoietic progenitor populations showed that Ts65Dn mice possessed fewer functional hematopoietic stem cells and a significantly decreased percentage of bone marrow lymphoid progenitors. Increased reactive oxygen species and markers of oxidative stress were detected in hematopoietic stem cell populations and were associated with a loss of quiescence. Bone marrow progenitor populations expressed diminished levels of the IL-7Rα chain, which was associated with decreased proliferation and increased apoptosis. Modulating oxidative stress in vitro suggested that oxidative stress selectively leads to decreased IL-7Rα expression, and inhibits the survival of IL-7Rα-expressing hematopoietic progenitors, potentially linking increased reactive oxygen species and immunopathology. Innovation The study results identify a link between oxidative stress and diminished IL-7Rα expression and function. Further, the data suggest that this decrease in IL-7Rα is associated with defective hematopoietic development in Down Syndrome. Conclusion The data suggest that hematopoietic stem and lymphoid progenitor cell defects underlie immune dysfunction in DS and that increased oxidative stress and reduced cytokine signaling may alter hematologic development in Ts65Dn mice. Antioxid. Redox Signal. 15, 2083–2094. PMID:21504363

Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

PubMed Central

Amr, Sherif M.; Gouda, Ashraf; Koptan, Wael T.; Galal, Ahmad A.; Abdel-Fattah, Dina Sabry; Rashed, Laila A.; Atta, Hazem M.; Abdel-Aziz, Mohammad T.

2014-01-01

Objective To investigate the effect of bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells. Methods In 14 patients with chronic paraplegia caused by spinal cord injury, cord defects were grafted and stem cells injected into the whole construct and contained using a chitosan-laminin paste. Patients were evaluated using the International Standards for Classification of Spinal Cord Injuries. Results Chitosan disintegration leading to post-operative seroma formation was a complication. Motor level improved four levels in 2 cases and two levels in 12 cases. Sensory-level improved six levels in two cases, five levels in five cases, four levels in three cases, and three levels in four cases. A four-level neurological improvement was recorded in 2 cases and a two-level neurological improvement occurred in 12 cases. The American Spinal Impairment Association (ASIA) impairment scale improved from A to C in 12 cases and from A to B in 2 cases. Although motor power improvement was recorded in the abdominal muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee extensors (2–3 grades), ankle dorsiflexors (1–2 grades), long toe extensors (1–2 grades), and plantar flexors (0–2 grades), this improvement was too low to enable them to stand erect and hold their knees extended while walking unaided. Conclusion Mesenchymal stem cell-derived neural stem cell-like cell transplantation enhances recovery in chronic spinal cord injuries with defects bridged by sural nerve grafts combined with a chitosan-laminin scaffold. PMID:24090088

Periodontal tissue regeneration by combined implantation of adipose tissue-derived stem cells and platelet-rich plasma in a canine model.

PubMed

Tobita, Morikuni; Uysal, Cagri A; Guo, Xin; Hyakusoku, Hiko; Mizuno, Hiroshi

2013-12-01

One goal of periodontal therapy is to regenerate periodontal tissues. Stem cells, growth factors and scaffolds and biomaterials are vital for the restoration of the architecture and function of complex tissues. Adipose tissue-derived stem cells (ASCs) are an ideal population of stem cells for practical regenerative medicine. In addition, platelet-rich plasma (PRP) can be useful for its ability to stimulate tissue regeneration. PRP contains various growth factors and may be useful as a cell carrier in stem cell therapies. The purpose of this study was to determine whether a mixture of ASCs and PRP promoted periodontal tissue regeneration in a canine model. Autologous ASCs and PRP were implanted into areas with periodontal tissue defects. Periodontal tissue defects that received PRP alone or non-implantation were also examined. Histologic, immunohistologic and x-ray studies were performed 1 or 2 months after implantation. The amount of newly formed bone and the scale of newly formed cementum in the region of the periodontal tissue defect were analyzed on tissue sections. The areas of newly formed bone and cementum were greater 2 months after implantation of ASCs and PRP than at 1 month after implantation, and the radiopacity in the region of the periodontal tissue defect increased markedly by 2 months after implantation. The ASCs and PRP group exhibited periodontal tissue with the correct architecture, including alveolar bone, cementum-like structures and periodontal ligament-like structures, by 2 months after implantation. These findings suggest that a combination of autologous ASCs and PRP promotes periodontal tissue regeneration that develops the appropriate architecture for this complex tissue. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Solid State Lighting Program (Falcon)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeks, Steven

2012-06-30

Over the past two years, KLA-Tencor and partners successfully developed and deployed software and hardware tools that increase product yield for High Brightness LED (HBLED) manufacturing and reduce product development and factory ramp times. This report summarizes our development effort and details of how the results of the Solid State Light Program (Falcon) have started to help HBLED manufacturers optimize process control by enabling them to flag and correct identified killer defect conditions at any point of origin in the process manufacturing flow. This constitutes a quantum leap in yield management over current practice. Current practice consists of die dispositioningmore » which is just rejection of bad die at end of process based upon probe tests, loosely assisted by optical in-line monitoring for gross process deficiencies. For the first time, and as a result of our Solid State Lighting Program, our LED manufacturing partners have obtained the software and hardware tools that optimize individual process steps to control killer defects at the point in the processes where they originate. Products developed during our two year program enable optimized inspection strategies for many product lines to minimize cost and maximize yield. The Solid State Lighting Program was structured in three phases: i) the development of advanced imaging modes that achieve clear separation between LED defect types, improves signal to noise and scan rates, and minimizes nuisance defects for both front end and back end inspection tools, ii) the creation of defect source analysis (DSA) software that connect the defect maps from back-end and front-end HBLED manufacturing tools to permit the automatic overlay and traceability of defects between tools and process steps, suppress nuisance defects, and identify the origin of killer defects with process step and conditions, and iii) working with partners (Philips Lumileds) on product wafers, obtain a detailed statistical correlation of automated defect and DSA map overlay to failed die identified using end product probe test results. Results from our two year effort have led to “automated end-to-end defect detection” with full defect traceability and the ability to unambiguously correlate device killer defects to optically detected features and their point of origin within the process. Success of the program can be measured by yield improvements at our partner’s facilities and new product orders.« less

Amniotic Fluid-Derived Stem Cells for Cardiovascular Tissue Engineering Applications

PubMed Central

Petsche Connell, Jennifer; Camci-Unal, Gulden; Khademhosseini, Ali

2013-01-01

Recent research has demonstrated that a population of stem cells can be isolated from amniotic fluid removed by amniocentesis that are broadly multipotent and nontumorogenic. These amniotic fluid-derived stem cells (AFSC) could potentially provide an autologous cell source for treatment of congenital defects identified during gestation, particularly cardiovascular defects. In this review, the various methods of isolating, sorting, and culturing AFSC are compared, along with techniques for inducing differentiation into cardiac myocytes and endothelial cells. Although research has not demonstrated complete and high-yield cardiac differentiation, AFSC have been shown to effectively differentiate into endothelial cells and can effectively support cardiac tissue. Additionally, several tissue engineering and regenerative therapeutic approaches for the use of these cells in heart patches, injection after myocardial infarction, heart valves, vascularized scaffolds, and blood vessels are summarized. These applications show great promise in the treatment of congenital cardiovascular defects, and further studies of isolation, culture, and differentiation of AFSC will help to develop their use for tissue engineering, regenerative medicine, and cardiovascular therapies. PMID:23350771

The analysis method of the DRAM cell pattern hotspot

NASA Astrophysics Data System (ADS)

Lee, Kyusun; Lee, Kweonjae; Chang, Jinman; Kim, Taeheon; Han, Daehan; Hong, Aeran; Kim, Yonghyeon; Kang, Jinyoung; Choi, Bumjin; Lee, Joosung; Lee, Jooyoung; Hong, Hyeongsun; Lee, Kyupil; Jin, Gyoyoung

2015-03-01

It is increasingly difficult to determine degree of completion of the patterning and the distribution at the DRAM Cell Patterns. When we research DRAM Device Cell Pattern, there are three big problems currently, it is as follows. First, due to etch loading, it is difficult to predict the potential defect. Second, due to under layer topology, it is impossible to demonstrate the influence of the hotspot. Finally, it is extremely difficult to predict final ACI pattern by the photo simulation, because current patterning process is double patterning technology which means photo pattern is completely different from final etch pattern. Therefore, if the hotspot occurs in wafer, it is very difficult to find it. CD-SEM is the most common pattern measurement tool in semiconductor fabrication site. CD-SEM is used to accurately measure small region of wafer pattern primarily. Therefore, there is no possibility of finding places where unpredictable defect occurs. Even though, "Current Defect detector" can measure a wide area, every chip has same pattern issue, the detector cannot detect critical hotspots. Because defect detecting algorithm of bright field machine is based on image processing, if same problems occur on compared and comparing chip, the machine cannot identify it. Moreover this instrument is not distinguished the difference of distribution about 1nm~3nm. So, "Defect detector" is difficult to handle the data for potential weak point far lower than target CD. In order to solve those problems, another method is needed. In this paper, we introduce the analysis method of the DRAM Cell Pattern Hotspot.

Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration

PubMed Central

Flores, Natasha M.; Oviedo, Néstor J.; Sage, Julien

2016-01-01

The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians. PMID:27542689

Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration.

PubMed

Flores, Natasha M; Oviedo, Néstor J; Sage, Julien

2016-10-01

The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Histopathological Comparison between Bone Marrow- and Periodontium-derived Stem Cells for Bone Regeneration in Rabbit Calvaria.

PubMed

Kadkhoda, Z; Safarpour, A; Azmoodeh, F; Adibi, S; Khoshzaban, A; Bahrami, N

2016-01-01

Periodontitis is an important oral disease. Stem cell therapy has found its way in treatment of many diseases. To evaluate the regenerative potential of periodontal ligament-derived stem cells (PDLSCs) and osteoblast differentiated from PDLSC in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and pre-osteoblasts in calvarial defects. After proving the existence of surface markers by flow cytometry, BM-MSCs were differentiated into osteoblasts. 5 defects were made on rabbit calvaria. 3 of them were first covered with collagen membrane and then with BM-MSCs, PDLSCs, and pre-osteoblasts. The 4(th) defect was filled with collagen membrane and the 5(th) one was served as control. After 4 weeks, histological (quantitative) and histomorphological (qualitative) surveys were performed. Both cell lineages were positive for CD-90 cell marker, which was specifically related to stem cells. Alizarin red staining was done for showing mineral material. RT-PCR set up for the expression of Cbfa1 gene, BMP4 gene, and PGLAP gene, confirmed osteoblast differentiation. The findings indicated that although PDLSCs and pre-osteoblasts could be used for bone regeneration, the rate of regeneration in BM-MSCs-treated cavities was more significant (p<0.0001). The obtained results are probably attributable to the effective micro-environmental signals caused by different bone types and the rate of cell maturation.

Influence of prosthesis design and implantation technique on implant stresses after cementless revision THR

PubMed Central

2011-01-01

Background Femoral offset influences the forces at the hip and the implant stresses after revision THR. For extended bone defects, these forces may cause considerable bending moments within the implant, possibly leading to implant failure. This study investigates the influences of femoral anteversion and offset on stresses in the Wagner SL revision stem implant under varying extents of bone defect conditions. Methods Wagner SL revision stems with standard (34 mm) and increased offset (44 mm) were virtually implanted in a model femur with bone defects of variable extent (Paprosky I to IIIb). Variations in surgical technique were simulated by implanting the stems each at 4° or 14° of anteversion. Muscle and joint contact forces were applied to the reconstruction and implant stresses were determined using finite element analyses. Results Whilst increasing the implant's offset by 10 mm led to increased implant stresses (16.7% in peak tensile stresses), altering anteversion played a lesser role (5%). Generally, larger stresses were observed with reduced bone support: implant stresses increased by as much as 59% for a type IIIb defect. With increased offset, the maximum tensile stress was 225 MPa. Conclusion Although increased stresses were observed within the stem with larger offset and increased anteversion, these findings indicate that restoration of offset, key to restoring joint function, is unlikely to result in excessive implant stresses under routine activities if appropriate fixation can be achieved. PMID:21569522

Multichip imager with improved optical performance near the butt region

NASA Technical Reports Server (NTRS)

Kinnard, Kenneth P. (Inventor); Strong, Jr., Richard T. (Inventor); Goldfarb, Samuel (Inventor); Tower, John R. (Inventor)

1991-01-01

A compound imager consists of two or more individual chips, each with at least one line array of sensors thereupon. Each chip has a glass support plate attached to the side from which light reaches the line arrays. The chips are butted together end-to-end to make large line arrays of sensors. Because of imperfections in cutting, the butted surfaces define a gap. Light entering in the region of the gap is either lost or falls on an individual imager other than the one for which it is intended. This results in vignetting and/or crosstalk near the butted region. The gap is filled with an epoxy resin or other similar material which, when hardened, has an index of referaction near that of the glass support plate.

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Chauveau, J.; Del Buono, L.; Genat, J. F.; Lebbolo, H.; Roos, L.; Zhang, B.; Beigbeder, C.; Bernier, R.; Breton, D.; Caceres, T.; Chase, R.; Ducorps, A.; Hrisoho, A.; Imbert, P.; Sen, S.; Tocut, V.; Truong, K.; Wormser, G.; Zomer, F.; Bonneaud, G.; Dohou, F.; Gastaldi, F.; Matricon, P.; Renard, C.; Thiebaux, C.; Vasileiadis, G.; Verderi, M.; Oxoby, G.; Va'Vra, J.; Warner, D.; Wilson, R. J.

1999-08-01

The detector of Internally Reflected Cherenkov light (DIRC) of the BaBar detector (SLAC Stanford, USA) measures better than 1 ns the arrival time of Cherenkov photoelectrons, detected in a 11 000 phototubes array and their amplitude spectra. It mainly comprises of 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom Analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom Digital TDC chips for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected from up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test of the pre-production chips have been performed as well as system tests.

Matrilin-3 codelivery with adipose-derived mesenchymal stem cells promotes articular cartilage regeneration in a rat osteochondral defect model.

PubMed

Muttigi, Manjunatha S; Kim, Byoung Ju; Choi, Bogyu; Yoshie, Arai; Kumar, Hemant; Han, Inbo; Park, Hansoo; Lee, Soo-Hong

2018-03-01

Matrilin-3 is an essential extracellular matrix component present only in cartilaginous tissues. Matrilin-3 exerts chondroprotective effects by regulating an anti-inflammatory function and extracellular matrix components. We hypothesized that the codelivery of matrilin-3 with infrapatellar adipose-tissue-derived mesenchymal stem cells (Ad-MSCs) may enhance articular cartilage regeneration. Matrilin-3 treatment of Ad-MSCs in serum-free media induced collagen II and aggrecan expression, and matrilin-3 in chondrogenic media also enhanced in vitro chondrogenic differentiation. Next, the in vivo effect of matrilin-3 codelivery with Ad-MSCs on cartilage regeneration was assessed in an osteochondral defect model in Sprague Dawley rats: Ad-MSCs and hyaluronic acid were implanted at the defect site with or without matrilin-3 (140, 280, and 700 ng). Safranin O staining revealed that matrilin-3 (140 and 280 ng) treatment significantly improved cartilage regeneration and glycosaminoglycan accumulation. In the animals treated with 140-ng matrilin-3, in particular, the defect site exhibited complete integration with surrounding tissue and a smooth glistening surface. The International Cartilage Repair Society macroscopic and O'Driscoll microscopic scores for regenerated cartilage were furthermore shown to be considerably higher for this group (matrilin-3; 140 ng) compared with the other groups. Furthermore, the defects treated with 140-ng matrilin-3 revealed significant hyaline-like cartilage regeneration in the osteochondral defect model; in contrast, the defects treated with 700-ng matrilin-3 exhibited drastically reduced cartilage regeneration with mixed hyaline-fibrocartilage morphology. Codelivery of matrilin-3 with Ad-MSCs significantly influenced articular cartilage regeneration, supporting the potential use of this tissue-specific protein for a cartilage-targeted stem cell therapy. Copyright © 2017 John Wiley & Sons, Ltd.

Topological defects control collective dynamics in neural progenitor cell cultures

NASA Astrophysics Data System (ADS)

Kawaguchi, Kyogo; Kageyama, Ryoichiro; Sano, Masaki

2017-04-01

Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and -1/2 (half-integer due to the nematic feature that arises from the head-tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from -1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.

Senescence sweetening of chip and fry processing potatoes

USDA-ARS?s Scientific Manuscript database

Potato storage makes the crop available over an extended time period, but increases financial risk to growers and end users. Senescence sweetening limits storage duration for chip and fry processing potatoes because it results in an unacceptable accumulation of reducing sugars that result in dark-co...

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

PubMed Central

Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

2015-01-01

Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.

PubMed

Rao, Yang; Cui, Jihong; Yin, Lu; Liu, Wei; Liu, Wenguang; Sun, Mei; Yan, Xingrong; Wang, Ling; Chen, Fulin

2016-10-22

Embryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo. The stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model. Mouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs. pESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.

Barriers for Deriving Transgene-Free Pig iPS Cells with Episomal Vectors.

PubMed

Du, Xuguang; Feng, Tao; Yu, Dawei; Wu, Yuanyuan; Zou, Huiying; Ma, Shuangyu; Feng, Chong; Huang, Yongye; Ouyang, Hongsheng; Hu, Xiaoxiang; Pan, Dengke; Li, Ning; Wu, Sen

2015-11-01

To date no authentic embryonic stem cell (ESC) line or germline-competent-induced pluripotent stem cell (iPSC) line has been established for large animals. Despite this fact, there is an impression in the field that large animal ESCs or iPSCs are as good as mouse counterparts. Clarification of this issue is important for a healthy advancement of the stem cell field. Elucidation of the causes of this failure in obtaining high quality iPSCs/ESCs may offer essential clues for eventual establishment of authentic ESCs for large animals including humans. To this end, we first generated porcine iPSCs using nonintegrating replicating episomal plasmids. Although these porcine iPSCs met most pluripotency criteria, they could neither generate cloned piglets through nuclear transfer, nor contribute to later stage chimeras through morula injections or aggregations. We found that the reprogramming genes in iPSCs could not be removed even under negative selection, indicating they are required to maintain self-renewal. The persistent expression of these genes in porcine iPSCs in turn caused differentiation defects in vivo. Therefore, incomplete reprogramming manifested by a reliance on sustained expression of exogenous-reprogramming factors appears to be the main reason for the inability of porcine iPSCs to form iPSC-derived piglets. © 2015 AlphaMed Press.

Fundamental study of microelectronic chip response under laser ultrasonic-interferometric inspection using C-scan method

NASA Astrophysics Data System (ADS)

Yang, Lei; Gong, Jie; Ume, I. Charles

2014-02-01

In modern surface mount packaging technologies, such as flip chips, chip scale packages, and ball grid arrays(BGA), chips are attached to the substrates/printed wiring board (PWB) using solder bump interconnections. The quality of solder bumps between the chips and the substrate/board is difficult to inspect. Laser ultrasonic-interferometric technique was proved to be a promising approach for solder bump inspection because of its noncontact and nondestructive characteristics. Different indicators extracted from received signals have been used to predict the potential defects, such as correlation coefficient, error ratio, frequency shifting, etc. However, the fundamental understanding of the chip behavior under laser ultrasonic inspection is still missing. Specifically, it is not sure whether the laser interferometer detected out-of-plane displacements were due to wave propagation or structural vibration when the chip was excited by pulsed laser. Plus, it is found that the received signals are chip dependent. Both challenges impede the interpretation of acquired signals. In this paper, a C-scan method was proposed to study the underlying phenomenon during laser ultrasonic inspection. The full chip was inspected. The response of the chip under laser excitation was visualized in a movie resulted from acquired signals. Specifically, a BGA chip was investigated to demonstrate the effectiveness of this method. By characterizing signals using discrete wavelet transform(DWT), both ultrasonic wave propagation and vibration were observed. Separation of them was successfully achieved using ideal band-pass filter and visualized in resultant movies, too. The observed ultrasonic waves were characterized and their respective speeds were measured by applying 2-D FFT. The C-scan method, combined with different digital signal processing techniques, was proved to be an very effective methodology to learn the behavior of chips under laser excitation. This general procedure can be applied to any unknown chip before inspection. A wealth of information can be provided by this learning procedure, which greatly benefits the interpretation of inspection signals afterwards.

Cassava chip (Manihot esculenta Crantz) as an energy source for ruminant feeding.

PubMed

Wanapat, Metha; Kang, Sungchhang

2015-12-01

Cassava ( Manihot esculenta Crantz) is widely grown in sub-tropical and tropical areas, producing roots as an energy source while the top biomass including leaves and immature stems can be sun-dried and used as cassava hay. Cassava roots can be processed as dried chip or pellet. It is rich in soluble carbohydrate (75 to 85%) but low in crude protein (2 to 3%). Its energy value is comparable to corn meal but has a relatively higher rate of rumen degradation. Higher levels of non-protein nitrogen especially urea (1 to 4%) can be successfully incorporated in concentrates containing cassava chip as an energy source. Cassava chip can also be processed with urea and other ingredients (tallow, sulfur, raw banana meal, cassava hay, and soybean meal) to make products such as cassarea, cassa-ban, and cassaya. Various studies have been conducted in ruminants using cassava chip to replace corn meal in the concentrate mixtures and have revealed satisfactory results in rumen fermentation efficiency and the subsequent production of meat and milk. In addition, it was advantageous when used in combination with rice bran in the concentrate supplement. Practical home-made-concentrate using cassava chip can be easily prepared for use on farms. A recent development has involved enriching protein in cassava chips, yielding yeast fermented cassava chip protein (YEFECAP) of up to 47.5% crude protein, which can be used to replace soybean meal. It is therefore, recommended to use cassava chip as an alternative source of energy to corn meal when the price is economical and it is locally available.

Expression of Pluripotency Genes in Chondrocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells

PubMed Central

Stelcer, Ewelina; Kulcenty, Katarzyna; Rucinski, Marcin; Jopek, Karol; Trzeciak, Tomasz; Richter, Magdalena; Wroblewska, Joanna P.; Suchorska, Wiktoria M.

2018-01-01

Human induced pluripotent stem cells (hiPSCs) constitute an important breakthrough in regenerative medicine, particularly in orthopedics, where more effective treatments are urgently needed. Despite the promise of hiPSCs only limited data on in vitro chondrogenic differentiation of hiPSCs are available. Therefore, we compared the gene expression profile of pluripotent genes in hiPSC-derived chondrocytes (ChiPS) to that of an hiPSC cell line created by our group (GPCCi001-A). The results are shown on heatmaps and plots and confirmed by Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) analysis. Unlike the ChiPS, our GPCCi001-A cells maintained their pluripotency state during long-term culture, thus demonstrating that this cell line was comprised of stable, fully pluripotent hiPSCs. Moreover, these chondrocyte-like cells not only presented features that are characteristic of chondrocytes, but they also lost their pluripotency, which is an important advantage in favor of using this cell line in future clinical studies. PMID:29439516

Intramedullary Stabilization of Periprosthetic Fractures of the Femur Taking Special Account of Bone Defects.

PubMed

Eingartner, Christoph; Volkmann, Rüdiger; Ochs, Uwe; Egetemeyr, Daniel; Weise, Kuno

2007-10-01

Healing of the periprosthetic fracture and area of defective bone by the bone healing mechanisms of intramedullary stabilization. Reconstruction of the correct length, axial alignment, and rotation of the fractured femoral shaft by anchoring a revision stem in the intact femoral diaphysis. Periprosthetic femoral shaft fracture in the region of the prosthetic stem combined with preexistent loosening and/or defect in the periprosthetic bone bed (Vancouver classification type B2 and B3). General contraindications, local infection. Lateral transmuscular approach to the femoral shaft. Longitudinal osteotomy of the proximal femur taking the geometry of the fracture into account. Opening of an anterior "bone shell". Removal of the loose prosthetic stem and cement. Debridement. Preparation of the femoral diaphysis and insertion of a distally anchored revision stem. Distal locking. Repositioning of the "bone shell", reduction of the fracture, and retention with cerclage wires. Bed rest for approximately 1 week, mobilization with 20 kg partial weight bearing for 12 weeks, gradual increase in weight bearing with radiologic checks on progress, removal of the distal locking bolts after 12-24 months at the earliest. 21 patients (13 women, eight men) aged between 43 and 86 years (mean age: 71.2 years) with periprosthetic fracture of the femur, additional loosening of the stem in eight cases (Vancouver B2) and additional bone loss in 13 cases (Vancouver B3). Postoperative complications: two fractures following another fall (repeat operations: one replacement, one plate), four revisions due to subsidence of the stem (three replacements involving change to a standard stem with healed proximal femur, one replacement with another interlocked revision stem). Bone healing occurred for all fractures after a mean 5.6 months (3-11 months). Follow- up examination after a mean 4.5 years: all patients were able to walk, average Harris Score 70.5 points (29- 95 points).

Intramedullary stabilization of periprosthetic fractures of the femur taking special account of bone defects.

PubMed

Eingartner, Christoph; Volkmann, Rüdiger; Ochs, Uwe; Egetemeyr, Daniel; Weise, Kuno

2006-10-01

Healing of the periprosthetic fracture and area of defective bone by the bone healing mechanisms of intramedullary stabilization. Reconstruction of the correct length, axial alignment, and rotation of the fractured femoral shaft by anchoring a revision stem in the intact femoral diaphysis. Periprosthetic femoral shaft fracture in the region of the prosthetic stem combined with preexistent loosening and/or defect in the periprosthetic bone bed (Vancouver classification type B2 and B3). General contraindications, local infection. Lateral transmuscular approach to the femoral shaft. Longitudinal osteotomy of the proximal femur taking the geometry of the fracture into account. Opening of an anterior "bone shell". Removal of the loose prosthetic stem and cement. Debridement. Preparation of the femoral diaphysis and insertion of a distally anchored revision stem. Distal locking. Repositioning of the "bone shell", reduction of the fracture, and retention with cerclage wires. Bed rest for approximately 1 week, mobilization with 20 kg partial weight bearing for 12 weeks, gradual increase in weight bearing with radiologic checks on progress, removal of the distal locking bolts after 12-24 months at the earliest. 21 patients (13 women, eight men) aged between 43 and 86 years (mean age: 71.2 years) with periprosthetic fracture of the femur, additional loosening of the stem in eight cases (Vancouver B2) and additional bone loss in 13 cases (Vancouver B3). Postoperative complications: two fractures following another fall (repeat operations: one replacement, one plate), four revisions due to subsidence of the stem (three replacements involving change to a standard stem with healed proximal femur, one replacement with another interlocked revision stem). Bone healing occurred for all fractures after a mean 5.6 months (3-11 months). Follow-up examination after a mean 4.5 years: all patients were able to walk, average Harris Score 70.5 points (29-95 points).

Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect

PubMed Central

Behnia, Ali; Haghighat, Abbas; Talebi, Ardeshir; Nourbakhsh, Nosrat; Heidari, Fariba

2014-01-01

AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth (SHED) transplanted for bone regeneration in the dog mandibular defect. METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-and-through defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level. RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue (P = 0.248), woven bone (P = 0.248) and compact bone (P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period. CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs. PMID:25258673

Three-dimensional imaging of individual point defects using selective detection angles in annular dark field scanning transmission electron microscopy.

PubMed

Johnson, Jared M; Im, Soohyun; Windl, Wolfgang; Hwang, Jinwoo

2017-01-01

We propose a new scanning transmission electron microscopy (STEM) technique that can realize the three-dimensional (3D) characterization of vacancies, lighter and heavier dopants with high precision. Using multislice STEM imaging and diffraction simulations of β-Ga 2 O 3 and SrTiO 3 , we show that selecting a small range of low scattering angles can make the contrast of the defect-containing atomic columns substantially more depth-dependent. The origin of the depth-dependence is the de-channeling of electrons due to the existence of a point defect in the atomic column, which creates extra "ripples" at low scattering angles. The highest contrast of the point defect can be achieved when the de-channeling signal is captured using the 20-40mrad detection angle range. The effect of sample thickness, crystal orientation, local strain, probe convergence angle, and experimental uncertainty to the depth-dependent contrast of the point defect will also be discussed. The proposed technique therefore opens new possibilities for highly precise 3D structural characterization of individual point defects in functional materials. Copyright © 2016 Elsevier B.V. All rights reserved.

Resolving individual Shockley partials of a dissociated dislocation by STEM

NASA Astrophysics Data System (ADS)

Iwata, Hiroyuki; Saka, Hiroyasu

2017-02-01

A practical method was developed to image detailed features of defects in a crystal using STEM. This method is essentially a STEM version of the conventional CTEM g/3g weak beam dark field (WBDF) method. The method was successfully applied to resolving individual Shockley partials of a dissociated dislocation in a Cu-6.44at.%Al alloy.

Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.

PubMed

Mawad, Damia; Figtree, Gemma; Gentile, Carmine

2017-01-01

The stem cell microenvironment or niche plays a critical role in the regulation of survival, differentiation and behavior of stem cells and their progenies. Recapitulating each aspect of the stem cell niche is therefore essential for their optimal use in in vitro studies and in vivo as future therapeutics in humans. Engineering of optimal conditions for three-dimensional stem cell culture includes multiple transient and dynamic physiological stimuli, such as blood flow and tissue stiffness. Bioprinting and microfluidics technologies, including organs-on-a-chip, are among the most recent approaches utilized to replicate the three-dimensional stem cell niche for human tissue fabrication that allow the integration of multiple levels of tissue complexity, including blood flow. This chapter focuses on the physico-chemical and genetic cues utilized to engineer the stem cell niche and provides an overview on how both bioprinting and microfluidics technologies are improving our knowledge in this field for both disease modeling and tissue regeneration, including drug discovery and toxicity high-throughput assays and stem cell-based therapies in humans.

Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis

PubMed Central

Liang, Dong; Wang, Xia; Mittal, Ashok; Dhiman, Sonam; Hou, Shuan-Yu; Degenhardt, Karl; Astrof, Sophie

2014-01-01

Integrin α5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin α5β1 in cardiovascular development, we used the Mesp1Cre knock-in strain of mice to ablate integrin α5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin α5β1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures. PMID:25242040

Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†

PubMed Central

Mukherjee, Kusumika; Ishii, Kana; Pillalamarri, Vamsee; Kammin, Tammy; Atkin, Joan F.; Hickey, Scott E.; Xi, Qiongchao J.; Zepeda, Cinthya J.; Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.; Maas, Richard L.; Liao, Eric C.

2016-01-01

CAPZB is an actin-capping protein that caps the growing end of F-actin and modulates the cytoskeleton and tethers actin filaments to the Z-line of the sarcomere in muscles. Whole-genome sequencing was performed on a subject with micrognathia, cleft palate and hypotonia that harbored a de novo, balanced chromosomal translocation that disrupts the CAPZB gene. The function of capzb was analyzed in the zebrafish model. capzb−/− mutants exhibit both craniofacial and muscle defects that recapitulate the phenotypes observed in the human subject. Loss of capzb affects cell morphology, differentiation and neural crest migration. Differentiation of both myogenic stem cells and neural crest cells requires capzb. During palate morphogenesis, defective cranial neural crest cell migration in capzb−/− mutants results in loss of the median cell population, creating a cleft phenotype. capzb is also required for trunk neural crest migration, as evident from melanophores disorganization in capzb−/− mutants. In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. PMID:26758871

Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs)

PubMed Central

Matthias, Nadine; Hunt, Samuel D.; Wu, Jianbo; Lo, Jonathan; Smith Callahan, Laura A.; Li, Yong; Huard, Johnny; Darabi, Radbod

2018-01-01

Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA)muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method. Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding. These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects. PMID:29331939

Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Gwak, Eun-Hye; Rhee, Sang-Hoon; Lee, Jeong-Cheol; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2015-01-01

Peri-implantitis is a chronic inflammatory process with advanced bone loss and impaired healing potential. For peri-implantitis treatment, tissue engineering can be applied to enhance bone regeneration of peri-implant defects. This study aimed to evaluate ex vivo bone morphogenetic protein 2 (BMP2) gene delivery using canine periodontal ligament stem cells (PDLSCs) for regeneration of peri-implantitis defects. Canine PDLSCs were transduced with adenoviral vectors containing BMP2 (BMP2/PDLSCs). After peri-implantitis was induced by ligature placement in six beagle dogs, regenerative procedures were performed; hydroxyapatite (HA) particles and collagen gel with autologous canine PDLSCs (PDLSC group) or BMP2/PDLSCs (BMP/PDLSC group) or without cells (control group) were grafted into the defects and covered by an absorbable membrane. Three months later, the animals were sacrificed. In vitro, BMP2/PDLSCs showed similar levels of stem cell properties to PDLSCs, such as colony-forming efficiency and expression of MSC markers STRO-1 and CD 146. BMP2/PDLSCs produced BMP-2 until day 21 at a concentration of 4-8 ng/mL. In vivo, the BMP2/PDLSC group showed significantly more new bone formation and re-osseointegration in peri-implantitis defects compared to the other groups. In conclusion, ex vivo BMP2 gene delivery using PDLSCs enhanced new bone formation and re-osseointegration in peri-implantitis defects. © 2014 Wiley Periodicals, Inc.

Localized ridge defect augmentation using human pericardium membrane and demineralized bone matrix.

PubMed

Vidyadharan, Arun Kumar; Ravindran, Anjana

2014-01-01

Patient wanted to restore her lost teeth with implants in the lower left first molar and second premolar region. Cone beam computerized tomography (CBCT) revealed inadequate bone width and height around future implant sites. The extraction socket of second premolar area revealed inadequate socket healing with sparse bone fill after 4 months of extraction. To evaluate the clinical feasibility of using a collagen physical resorbable barrier made of human pericardium (HP) to augment localized alveolar ridge defects for the subsequent placement of dental implants. Ridge augmentation was done in the compromised area using Puros® demineralized bone matrix (DBM) Putty with chips and an HP allograft membrane. Horizontal (width) and vertical hard tissue measurements with CBCT were recorded on the day of ridge augmentation surgery, 4 month and 7 months follow-up. Intra oral periapical taken 1 year after implant installation showed minimal crestal bone loss. Bone volume achieved through guided bone regeneration was a gain of 4.8 mm horizontally (width) and 6.8 mm vertically in the deficient ridge within a period of 7 months following the procedure. The results suggested that HP Allograft membrane may be a suitable component for augmentation of localized alveolar ridge defects in conjunction with DBM with bone chips.

Strategy For Yield Control And Enhancement In VLSI Wafer Manufacturing

NASA Astrophysics Data System (ADS)

Neilson, B.; Rickey, D.; Bane, R. P.

1988-01-01

In most fully utilized integrated circuit (IC) production facilities, profit is very closely linked with yield. In even the most controlled manufacturing environments, defects due to foreign material are a still major contributor to yield loss. Ideally, an IC manufacturer will have ample engineering resources to address any problem that arises. In the real world, staffing limitations require that some tasks must be left undone and potential benefits left unrealized. Therefore, it is important to prioritize problems in a manner that will give the maximum benefit to the manufacturer. When offered a smorgasbord of problems to solve, most people (engineers included) will start with what is most interesting or the most comfortable to work on. By providing a system that accurately predicts the impact of a wide variety of defect types, a rational method of prioritizing engineering effort can be made. To that effect, a program was developed to determine and rank the major yield detractors in a mixed analog/digital FET manufacturing line. The two classical methods of determining yield detractors are chip failure analysis and defect monitoring on drop in test die. Both of these methods have short comings: 1) Chip failure analysis is painstaking and very time consuming. As a result, the sample size is very small. 2) Drop in test die are usually designed for device parametric analysis rather than defect analysis. To provide enough wafer real estate to do meaningful defect analysis would render the wafer worthless for production. To avoid these problems, a defect monitor was designed that provided enough area to detect defects at the same rate or better than the NMOS product die whose yield was to be optimized. The defect monitor was comprehensive and electrically testable using such equipment as the Prometrix LM25 and other digital testers. This enabled the quick accumulation of data which could be handled statistically and mapped individually. By scaling the defect densities found on the monitors to the known sensitivities of the product wafer, the defect types were ranked by defect limiting yield. (Limiting yield is the resultant product yield if there were no other failure mechanisms other than the type being considered.) These results were then compared to the product failure analysis results to verify that the monitor was finding the same types of defects in the same proportion which were troubling our product. Finally, the major defect types were isolated and reduced using the short loop capability of the monitor.

Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair.

PubMed

Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing; Liu, Huanhuan; Ouyang, Hong Wei

2014-10-01

Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair. ©AlphaMed Press.

Bone marrow-on-a-chip: Long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment.

PubMed

Sieber, Stefan; Wirth, Lorenz; Cavak, Nino; Koenigsmark, Marielle; Marx, Uwe; Lauster, Roland; Rosowski, Mark

2018-02-01

Multipotent haematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to date, no in vitro model exists that accurately mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, a novel three-dimensional coculture model is presented, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic multiorgan chip. The HSPCs were found to stay in their primitive state (CD34 + CD38 - ) and capable of granulocyte, erythrocyte, macrophage, megakaryocyte colony formation. Furthermore, a microenvironment was formed bearing molecular and structural similarity to the in vivo bone marrow niche containing extracellular matrix and signalling molecules known to play an important role in HSPC homeostasis. Here, a novel human in vitro bone marrow model is presented for the first time, capable of long-term culture of primitive HSPCs in a microfluidic environment. Copyright © 2017 John Wiley & Sons, Ltd.

Ultraviolet laser ablation as technique for defect repair of GaN-based light-emitting diodes

NASA Astrophysics Data System (ADS)

Passow, Thorsten; Kunzer, Michael; Pfeuffer, Alexander; Binder, Michael; Wagner, Joachim

2018-03-01

Defect repair of GaN-based light-emitting diodes (LEDs) by ultraviolet laser micromachining is reported. Percussion and helical drilling in GaN by laser ablation were investigated using 248 nm nanosecond and 355 nm picosecond pulses. The influence of laser ablation including different laser parameters on electrical and optical properties of GaN-based LED chips was evaluated. The results for LEDs on sapphire with transparent conductive oxide p-type contact on top as well as for thin-film LEDs are reported. A reduction of leakage current by up to six orders in magnitude and homogeneous luminance distribution after proper laser defect treatment were achieved.

Regeneration of periodontal tissues using allogeneic periodontal ligament stem cells in an ovine model.

PubMed

Mrozik, Krzysztof Marek; Wada, Naohisa; Marino, Victor; Richter, Ward; Shi, Songtao; Wheeler, Donna L; Gronthos, Stan; Bartold, P Mark

2013-11-01

To investigate the capacity of allogeneic periodontal ligament stem cells (PDLSCs) to regenerate periodontal tissues using an ovine periodontal defect model. Surgically created zero-wall dehiscence periodontal defects created in Merino sheep were filled with 1 × 10(7) allogeneic PDLSCs attached to Gelfoam(®), Gelfoam alone or left untreated. After 4 weeks, histological analysis was performed to assess periodontal regeneration. Allogeneic PDLSCs were well tolerated by recipient animals. The mean area of new alveolar bone was significantly greater in the PDLSC + Gelfoam treatment group compared with the defect-alone group. The PDLSC + Gelfoam and Gelfoam-only treatment groups displayed significantly greater length of new cementum and percentage of cementum regrowth compared with the defect-alone group. New Sharpey's fibers were generally more organized and significantly thicker within the PDLSC + Gelfoam treatment group. The PDLSC + Gelfoam treatment group also showed a trend of increased Sharpey's fiber attachment length compared with the Gelfoam-only and defect-alone groups. These studies support the potential use of allogeneic PDLSC preparations as viable therapies for periodontal regeneration in the clinical setting.

Bioprinting and Organ-on-Chip Applications Towards Personalized Medicine for Bone Diseases.

PubMed

Arrigoni, Chiara; Gilardi, Mara; Bersini, Simone; Candrian, Christian; Moretti, Matteo

2017-06-01

The skeleton supports and confers structure to the whole body but several pathological and traumatic conditions affect the bone tissue. Most of those pathological conditions are specific and different among different patients, such as bone defects due to traumatic injuries or bone remodeling alterations due to congenital diseases. In this context, the development of personalized therapies would be highly desirable. In recent years the advent of innovative techniques like bioprinting and microfluidic organ-on-chip raised hopes of achieving key tools helping the application of personalized therapies for bone diseases. In this review we will illustrate the latest progresses in the bioprinting of personalized bone grafts and generation of patient-specific bone-on-chip devices, describing current approaches and limitations and possible future improvements for more effective personalized bone grafts and disease models.

The use of type 1 collagen scaffold containing stromal cell-derived factor-1 to create a matrix environment conducive to partial-thickness cartilage defects repair.

PubMed

Zhang, Wei; Chen, Jialin; Tao, Jiadong; Jiang, Yangzi; Hu, Changchang; Huang, Lu; Ji, Junfeng; Ouyang, Hong Wei

2013-01-01

Despite the presence of cartilage-derived mesenchymal stem cells (C-MSCs) and synovial membrane-derived mesenchymal stem cells (SM-MSCs) populations, partial-thickness cartilage defects, in contrast to the full-thickness defects, are devoid of spontaneous repair capacity. This study aims to create an in situ matrix environment conducive to C-MSCs and SM-MSCs to promote cartilage self-repair. Spontaneous repair with MSCs migration into the defect area was observed in full-thickness defects, but not in partial-thickness defects in rabbit model. Ex vivo and in vitro studies showed that subchondral bone or type 1 collagen (col1) scaffold was more permissive for MSCs adhesion than cartilage or type 2 collagen (col2) scaffold and induced robust stromal cell-derived factors-1 (SDF-1) dependent migration of MSCs. Furthermore, creating a matrix environment with col1 scaffold containing SDF-1 enhanced in situ self-repair of partial-thickness defects in rabbit 6 weeks post-injury. Hence, the inferior self-repair capacity in partial-thickness defects is partially owing to the non-permissive matrix environment. Creating an in situ matrix environment conducive to C-MSCs and SM-MSCs migration and adhesion with col1 scaffold containing SDF-1 can be exploited to improve self-repair capacity of cartilage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Osteoinductive ceramics as a synthetic alternative to autologous bone grafting

PubMed Central

Yuan, Huipin; Fernandes, Hugo; Habibovic, Pamela; de Boer, Jan; Barradas, Ana M. C.; de Ruiter, Ad; Walsh, William R.; van Blitterswijk, Clemens A.; de Bruijn, Joost D.

2010-01-01

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of “smart” biomaterials. PMID:20643969

RF-Interrogated End-State Chip-Scale Atomic Clock

DTIC Science & Technology

2007-11-01

coherent population trapping,” Electronics Letters 37, (24), 1449-1451. [2] R. Lutwak , P. Vlitas, M. Varghese, M. Mescher, D. K. Serkland, and G. M...367. [9] R. Lutwak , D. Emmons, T. English, W. Riley, A. Duwel, M. Varghese, D. K. Serland, and G. M. Peake, 2003, “Chip-Scale Atomic Clock, Recent

Successful management of an equine carpal chip fracture by intra-articularly injected adipose-derived stromal vascular fraction after arthroscopic removal.

PubMed

Tyrnenopoulou, P; Karayannopoulou, M; Angelopoulou, S; Pyrros, A; Mparous, E; Koliakos, G; Diakakis, N

2016-01-01

Carpal chip fractures are common causes of lameness in racehorses. Due to disadvantages in surgical management, adjuvant treatment modalities are usually necessary. Adipose-derived stem cells (ADSCs) have the potential to differentiate into other cell types including bone and cartilage cells. Adipose-derived stromal vascular fraction (SVF) is produced during ADSCs isolation from adipose tissue. The purpose of this report was to present the successful management of a grade III chip fracture in the right carpus of a 5-year-old Thoroughbred gelding by intra-articularly injected autologous SVF one month after the arthroscopic removal of the fracture. This treatment resulted in lameness improvement and short rehabilitation period to previous racing activities. High performance levels and no recurrent injuries were recorded during a twenty month follow-up period.

Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration.

PubMed

Liu, Xiaolin; Yang, Yunlong; Li, Yan; Niu, Xin; Zhao, Bizeng; Wang, Yang; Bao, Chunyan; Xie, Zongping; Lin, Qiuning; Zhu, Linyong

2017-03-30

The regeneration of articular cartilage, which scarcely shows innate self-healing ability, is a great challenge in clinical treatment. Stem cell-derived exosomes (SC-Exos), an important type of extracellular nanovesicle, exhibit great potential for cartilage regeneration to replace stem cell-based therapy. Cartilage regeneration often takes a relatively long time and there is currently no effective administration method to durably retain exosomes at cartilage defect sites to effectively exert their reparative effect. Therefore, in this study, we exploited a photoinduced imine crosslinking hydrogel glue, which presents excellent operation ability, biocompatibility and most importantly, cartilage-integration, as an exosome scaffold to prepare an acellular tissue patch (EHG) for cartilage regeneration. It was found that EHG can retain SC-Exos and positively regulate both chondrocytes and hBMSCs in vitro. Furthermore, EHG can integrate with native cartilage matrix and promote cell deposition at cartilage defect sites, finally resulting in the promotion of cartilage defect repair. The EHG tissue patch therefore provides a novel, cell-free scaffold material for wound repair.

Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

PubMed

Guitart, Amelie V; Panagopoulou, Theano I; Villacreces, Arnaud; Vukovic, Milica; Sepulveda, Catarina; Allen, Lewis; Carter, Roderick N; van de Lagemaat, Louie N; Morgan, Marcos; Giles, Peter; Sas, Zuzanna; Gonzalez, Marta Vila; Lawson, Hannah; Paris, Jasmin; Edwards-Hicks, Joy; Schaak, Katrin; Subramani, Chithra; Gezer, Deniz; Armesilla-Diaz, Alejandro; Wills, Jimi; Easterbrook, Aaron; Coman, David; So, Chi Wai Eric; O'Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P; Pollard, Patrick J; Morton, Nicholas M; Finch, Andrew; Kranc, Kamil R

2017-03-06

Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1 / Hoxa9 -driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. © 2017 Guitart et al.

3D-Printing Composite Polycaprolactone-Decellularized Bone Matrix Scaffolds for Bone Tissue Engineering Applications.

PubMed

Rindone, Alexandra N; Nyberg, Ethan; Grayson, Warren L

2017-05-11

Millions of patients worldwide require bone grafts for treatment of large, critically sized bone defects from conditions such as trauma, cancer, and congenital defects. Tissue engineered (TE) bone grafts have the potential to provide a more effective treatment than current bone grafts since they would restore fully functional bone tissue in large defects. Most bone TE approaches involve a combination of stem cells with porous, biodegradable scaffolds that provide mechanical support and degrade gradually as bone tissue is regenerated by stem cells. 3D-printing is a key technique in bone TE that can be used to fabricate functionalized scaffolds with patient-specific geometry. Using 3D-printing, composite polycaprolactone (PCL) and decellularized bone matrix (DCB) scaffolds can be produced to have the desired mechanical properties, geometry, and osteoinductivity needed for a TE bone graft. This book chapter will describe the protocols for fabricating and characterizing 3D-printed PCL:DCB scaffolds. Moreover, procedures for culturing adipose-derived stem cells (ASCs) in these scaffolds in vitro will be described to demonstrate the osteoinductivity of the scaffolds.

High Tonnage Forest Biomass Production Systems from Southern Pine Energy Plantations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Steve; McDonald, Timothy; Fasina, Oladiran

In this study, a high-tonnage harvesting system designed specifically to operate efficiently in the expected stand types of a bioenergy scenario was built, deployed, and evaluated in a production setting. Stands on which the system was evaluated exhibited the heavy stocking levels (> 600 stems per acre) and tree size distributions with significant volume in small stems (down to 2” DBH) that were expected in the modified energy plantation silvicultural approach. The harvest system also was designed to be functional in the traditional plantation stands dominating the commercial forestry landscape in the region. The Tigercat 845D feller buncher, which wasmore » a prototype machine designed for the high tonnage harvest system, used a boom-mounted prototype DT1802 shear felling head and incorporated a number of options intended to maximize its small-stem productivity, including: a high-speed shear severing system that was cheaper to operate than a saw; a large-pocket felling head that allowed larger accumulations of small stems to be built before expending the time to drop them for the skidder; efficient, low ground pressure, tracked carrier system to decrease the amount of maneuvering, saving time and minimizing soil disturbance; and various energy-saving devices to lower fuel costs and minimize air quality impacts. Overall, the feller buncher represented a quantum advance in small-stem harvesting technology. Extensive testing showed the machine’s production rate to be relatively insensitive to piece size, much less so than comparable traditional equipment. In plantation stands, the feller buncher was able to produce approximately 100 green tons of biomass per productive machine hour (PMH), and in natural stands, it produced nearly 120 green tons per PMH. The ability of the high tonnage feller buncher to maintain high productivity in stands with smaller diameter stems is something that has not been achieved in previous feller buncher designs. The Tigercat 845D feller buncher is now a production machine for Tigercat and is being sold in their current product line. The high-speed felling system was paired with a Tigercat 630D skidder and high-capacity grapple; one that could match the felling productivity when pulling small stems. The harvesting system minimized hourly costs using a single, high-capacity skidder (with a single operator), rather than two smaller ones, which is the traditional practice. The skidder itself can be considered a mid-range size and had an engine no larger than other machines in its class, but it incorporated a very large capacity 25 ft2 grapple. The large grapple is well suited to grabbing and hauling a large bunch of small-diameter trees, as produced by the high tonnage feller buncher. The grapple worked effectively in larger stems as well, but its ability to carry large numbers of small stems meant the average payload did not drop as stand DBH decreased. Tests with the machine indicated its travel speeds were nearly the same as, or perhaps slightly better than, conventionally equipped skidders, but grapple capacity was 75% larger. Productivity and cost per ton of the new skidder were better than conventional skidders for average skid distances of any length greater than 100 feet. Measured skidder productivity was as high as 143 gt/PMH. Its productivity exceeded that of the high-capacity feller buncher for skid distances out to nearly 700 feet, so system productivity could be expected to remain high for stands of a size typical in the southern U.S. The Tigercat 630D skidder is a production machine for Tigercat and the large grapple can now be ordered by customers using it for small diameter trees. When the feller buncher and skidder are analyzed as a two-machine system, overall productivity is fixed at the level of the least productive machine. Results from a set of side-by-side tests in the same density stand with conventional feller bunchers and skidders showed that the high tonnage system produced 97 gt/PMH versus 68 gt/PMH for a comparable conventional system. Machine rate costs for felling and skidding were $2.31/gt and $3.72/gt for the high tonnage, and conventional systems, respectively. However, the most significant result of the project is that the high tonnage system was shown to be relatively insensitive to tree size. This ability to maintain felling and skidding productivity and cost as tree size decreases is a breakthrough in harvesting systems for southern pine plantations. The concept of transpirational drying of woody biomass was tested at an industrial scale at multiple locations during this project. Felled trees were allowed to dry in two scenarios: 1) in bunches where they were felled, and 2) in roadside piles. Although the wood piled in large piles at roadside did experience drying, the wood left in bunches experienced a greater moisture reduction. Drying times of 72 days in the late summer resulted in mean wood moisture content of 26% for skidder bunches and 39% for the large pile at roadside as compared to moisture contents of 55% to 58% for freshly cut trees. An existing whole-tree chipper, Precision 2675, was modified to allow production of chips smaller than the traditional pulp size chip (i.e. “microchips”). Feed rates and knife placements were retained in the new design, while additional pockets were incorporated in the chipper disk to allow the attachment of either four knives for pulp chips or eight knives for microchips. This design facilitated switching between the energy and pulp chip product options at relatively low expense (about ½ day downtime). Chipping of whole-trees into pulp chips and microchips with the Precision 2675 disk chipper resulted in average productivities of 79.5 gt/PMH and 70.7 gt/PMH, respectively. Production rates of the chipper were lower when producing microchips by about 10% relative to producing pulp chips, but rates were similar to those achievable when making clean pulp chips. Particle size analysis for clean pine microchips revealed 26.6% retention on a 13 mm (slightly less than 3/8-inch) round hole screen and 25.9% retention for whole-tree pine microchips. For comparison, clean pine pulp chips had 52.2% retained. Ash content (% dry basis) was 0.54% for clean pine microchips and 0.62% for whole-tree pine microchips. Ash content for clean pine pulp chips was 0.39%. For transpirationally-dried material there was 38.1% retention for whole-tree microchips on a 13mm screen compared to 70.1% for dried clean pulp chips. Ash content was 0.78% and 0.44% respectively for these two chip types. Clean pine microchips stored at roadside had 25.2% retention on a 13 mm screen and 0.50% ash content. For mixed species (pine and hardwood), whole-tree microchips had 25.1% retention on a 13 mm screen compared to 50.6% for whole-tree pulp chips. Ash content was 2.12% and 2.74% respectively for these two chip types. Clean hardwood microchips stored at roadside had 35.0% retention on a 13 mm screen and an ash content of 1.24%. There are two significant advantages to using transpirational drying: reduced transportation costs, and reduced drying costs (capital and operating costs) for the biorefinery. This project evaluated the potential to reduce transportation costs through transpirational drying, and it included a component that tested higher capacity chip trailers (23% larger volume) to be able to transport dry wood with a lower bulk density. For transpirationally-dried chips at 35% MC, the high-capacity trailers achieved loads with a mean payload of 24 tons with maximum payloads of 29 tons. The typical legal payload on this trailer is 28.5 tons. Therefore, the project demonstrated that it is possible to achieve maximum legal payloads on chip trailers with transpirationally dried wood. Assuming that the truck is loaded to the legal payload limit, the transportation costs of chips can be reduced from $15.91/dry ton (dt) for 56% MC wood to $10.77/dt for transpirationally dried wood at 35% MC (for an example 50-mile haul distance at $0.14 per one-way ton-mile). For longer haul distances, these savings in trucking costs become even more significant. These results have demonstrated how significant savings in transportation costs can be achieved through transpirational drying. Also, these results show that it may be possible to increase the procurement radius for a biorefinery by using transpirational drying. Further cost reductions can be realized by the biorefinery when drying costs are reduced. The goal of this study was development of a timber harvesting system as productive in stands optimized for biomass production as it was in stands grown for roundwood markets. If that goal is achieved, a logger can invest in a single suite of equipment and operate efficiently in any future silvicultural regime that might include energy feedstocks as an output. It was the premise of the study that a future biomass market would shift the age distribution and stem size in stands grown for energy downward, and the key strategy in developing a harvest system for that scenario would be creating one with logging costs relatively insensitive to tree size. Our vision for such a system included a felling machine with a large capacity head to minimize time spent building bunches, plus a skidder capable of moving large volumes of small trees. The study proposed building the system and testing it against existing equipment in stands similar to those envisioned as resulting from biomass-optimized silviculture. As stated previously, the new feller buncher and skidder evaluated on their own merits showed their designs were clearly a step in the right direction - their productivity was indeed high and less sensitive to reductions in stem size. Cost projections based on extensive time and production studies of the high tonnage and benchmark operations showed modest advantages in FOB costs of the new system in both ‘average’ and simulated ‘energy’ stands (7.7% and 9.5%, respectively). But it was clear, when coupled into a traditional logging system, the in-woods productivity advantage of the modified equipment was easily overwhelmed by inefficiencies in chipping or trucking. Some additional savings can be achieved by spreading the cost of the feller buncher over multiple chipping operations (another 7.5%), but generally, in stands with average DBH above 6 inches, the in-woods equipment was not limiting productivity, and costs were driven by chipping and transport. Our results were a positive step in lowering delivered cost of trees grown for energy purposes, but they also argue strongly for a more comprehensive approach in solving this issue. The procurement system in its entirety has to be optimized to take full advantage of the productivity gains achieved with the machines and transpirational drying techniques developed in this project. We have to understand the true costs of all logistical options, particularly those of the choice in chipping strategy and in truck allocation, both of which seemed, in this study, to be the greatest source of variability in cost, and often the most expensive operations as well.« less

Nano-volume drop patterning for rapid on-chip neuronal connect-ability assays.

PubMed

Petrelli, Alessia; Marconi, Emanuele; Salerno, Marco; De Pietri Tonelli, Davide; Berdondini, Luca; Dante, Silvia

2013-11-21

The ability of neurons to extend projections and to form physical connections among them (i.e., "connect-ability") is altered in several neuropathologies. The quantification of these alterations is an important read-out to investigate pathogenic mechanisms and for research and development of neuropharmacological therapies, however current morphological analysis methods are very time-intensive. Here, we present and characterize a novel on-chip approach that we propose as a rapid assay. Our approach is based on the definition on a neuronal cell culture substrate of discrete patterns of adhesion protein spots (poly-d-lysine, 23 ± 5 μm in diameter) characterized by controlled inter-spot separations of increasing distance (from 40 μm to 100 μm), locally adsorbed in an adhesion-repulsive agarose layer. Under these conditions, the connect-ability of wild type primary neurons from rodents is shown to be strictly dependent on the inter-spot distance, and can be rapidly documented by simple optical read-outs. Moreover, we applied our approach to identify connect-ability defects in neurons from a mouse model of 22q11.2 deletion syndrome/DiGeorge syndrome, by comparative trials with wild type preparations. The presented results demonstrate the sensitivity and reliability of this novel on-chip-based connect-ability approach and validate the use of this method for the rapid assessment of neuronal connect-ability defects in neuropathologies.

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

PubMed

Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

2016-01-01

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc.

The Proximal and Distal Femoral Canal Geometry Influences Cementless Stem Anchorage and Revision Hip and Knee Implant Stability.

PubMed

Heinecke, Markus; Rathje, Fabian; Layher, Frank; Matziolis, Georg

2018-05-01

Although cementless revision arthroplasty of the hip has become the gold standard, revision arthroplasty of the distal femur is controversial. This study evaluated the anchoring principles of different femoral revision stem designs in extended bone defect situations, taking into account the anatomical conditions of the proximal and distal femur, and the resulting primary stability. Cementless press-fit stems of 4 different designs were implanted in synthetic femurs. The specimens were analyzed by computed tomography and were tested considering axial/torsional stiffness and migration resistance. Different stem designs anchored in different femoral canal geometries achieved comparable primary stability. Despite considerably different anchorage lengths, no difference in migration behavior or stiffness was found. Both in the distal femur and in the proximal femur, the conical stems showed a combination of conical and 3-point anchorage. Regarding the cylindrical stem tested, a much shorter anchorage length was sufficient in the distal femur to achieve comparable primary stability. In the investigated osseous defect model, the stem design (conical vs cylindrical), not the geometry of the femoral canal (proximal vs distal), was decisive regarding the circumferential anchorage length. For the conical stems, it can be postulated that there are reserves available for achieving a conical-circular fixation as a result of the large contact length. For the cylindrical stems, only a small reserve for a stable anchorage can be assumed. [Orthopedics. 2018; 41(3):e369-e375.]. Copyright 2018, SLACK Incorporated.

High glucose alters the expression of genes involved in proliferation and cell-fate specification of embryonic neural stem cells.

PubMed

Fu, J; Tay, S S W; Ling, E A; Dheen, S T

2006-05-01

Maternal diabetes induces neural tube defects during embryogenesis. Since the neural tube is derived from neural stem cells (NSCs), it is hypothesised that in diabetic pregnancy neural tube defects result from altered expression of developmental control genes, leading to abnormal proliferation and cell-fate choice of NSCs. Cell viability, proliferation index and apoptosis of NSCs and differentiated cells from mice exposed to physiological or high glucose concentration medium were examined by a tetrazolium salt assay, 5-bromo-2'-deoxyuridine incorporation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and immunocytochemistry. Expression of developmental genes, including sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4), neurogenin 1/2 (Neurog1/2), achaete-scute complex-like 1 (Ascl1), oligodendrocyte transcription factor 1 (Olig1), oligodendrocyte lineage transcription factor 2 (Olig2), hairy and enhancer of split 1/5 (Hes1/5) and delta-like 1 (Dll1), was analysed by real-time RT-PCR. Proliferation index and neuronal specification in the forebrain of embryos at embryonic day 11.5 were examined histologically. High glucose decreased the proliferation of NSCs and differentiated cells. The incidence of apoptosis was increased in NSCs treated with high glucose, but not in the differentiated cells. High glucose also accelerated neuronal and glial differentiation from NSCs. The decreased proliferation index and early differentiation of neurons were evident in the telencephalon of embryos derived from diabetic mice. Exposure to high glucose altered the mRNA expression levels of Shh, Bmp4, Neurog1/2, Ascl1, Hes1, Dll1 and Olig1 in NSCs and Shh, Dll1, Neurog1/2 and Hes5 in differentiated cells. The changes in proliferation and differentiation of NSCs exposed to high glucose are associated with altered expression of genes that are involved in cell-cycle progression and cell-fate specification during neurulation. These changes may form the basis for the defective neural tube patterning observed in embryos of diabetic pregnancies.

In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins.

PubMed

Pakdaman, Yasaman; Sanchez-Guixé, Monica; Kleppe, Rune; Erdal, Sigrid; Bustad, Helene J; Bjørkhaug, Lise; Haugarvoll, Kristoffer; Tzoulis, Charalampos; Heimdal, Ketil; Knappskog, Per M; Johansson, Stefan; Aukrust, Ingvild

2017-04-30

Spinocerebellar ataxia, autosomal recessive 16 (SCAR16) is caused by biallelic mutations in the STIP1 homology and U-box containing protein 1 ( STUB1 ) gene encoding the ubiquitin E3 ligase and dimeric co-chaperone C-terminus of Hsc70-interacting protein (CHIP). It has been proposed that the disease mechanism is related to CHIP's impaired E3 ubiquitin ligase properties and/or interaction with its chaperones. However, there is limited knowledge on how these mutations affect the stability, folding, and protein structure of CHIP itself. To gain further insight, six previously reported pathogenic STUB1 variants (E28K, N65S, K145Q, M211I, S236T, and T246M) were expressed as recombinant proteins and studied using limited proteolysis, size-exclusion chromatography (SEC), and circular dichroism (CD). Our results reveal that N65S shows increased CHIP dimerization, higher levels of α-helical content, and decreased degradation rate compared with wild-type (WT) CHIP. By contrast, T246M demonstrates a strong tendency for aggregation, a more flexible protein structure, decreased levels of α-helical structures, and increased degradation rate compared with WT CHIP. E28K, K145Q, M211I, and S236T also show defects on structural properties compared with WT CHIP, although less profound than what observed for N65S and T246M. In conclusion, our results illustrate that some STUB1 mutations known to cause recessive SCAR16 have a profound impact on the protein structure, stability, and ability of CHIP to dimerize in vitro. These results add to the growing understanding on the mechanisms behind the disorder. © 2017 The Author(s).

An RFID tag system-on-chip with wireless ECG monitoring for intelligent healthcare systems.

PubMed

Wang, Cheng-Pin; Lee, Shuenn-Yuh; Lai, Wei-Chih

2013-01-01

This paper presents a low-power wireless ECG acquisition system-on-chip (SoC), including an RF front-end circuit, a power unit, an analog front-end circuit, and a digital circuitry. The proposed RF front-end circuit can provide the amplitude shift keying demodulation and distance to digital conversion to accurately receive the data from the reader. The received data will wake up the power unit to provide the required supply voltages of analog front-end (AFE) and digital circuitry. The AFE, including a pre-amplifier, an analog filter, a post-amplifier, and an analog-to-digital converter, is used for the ECG acquisition. Moreover, the EPC Class I Gen 2 UHF standard is employed in the digital circuitry for the handshaking of communication and the control of the system. The proposed SoC has been implemented in 0.18-µm standard CMOS process and the measured results reveal the communication is compatible to the RFID protocol. The average power consumption for the operating chip is 12 µW. Using a Sony PR44 battery to the supply power (605mAh@1.4V), the RFID tag SoC operates continuously for about 50,000 hours (>5 years), which is appropriate for wireless wearable ECG monitoring systems.

Sugar metabolism, chip color, invertase activity, and gene expression during long-term cold storage of potato (Solanum tuberosum) tubers from wild-type and vacuolar invertase silencing lines of Katahdin.

PubMed

Wiberley-Bradford, Amy E; Busse, James S; Jiang, Jiming; Bethke, Paul C

2014-11-16

Storing potato tubers at low temperatures minimizes sprouting and disease but can cause an accumulation of reducing sugars in a process called cold-induced sweetening. Tubers with increased amounts of reducing sugars produce dark-colored, bitter-tasting fried products with elevated amounts of acrylamide, a possible carcinogen. Vacuolar invertase (VInv), which converts sucrose produced by starch breakdown to glucose and fructose, is the key determinant of reducing sugar accumulation during cold-induced sweetening. In this study, wild-type tubers and tubers in which VInv expression was reduced by RNA interference were used to investigate time- and temperature-dependent changes in sugar contents, chip color, and expression of VInv and other genes involved in starch metabolism in tubers during long-term cold storage. VInv activities and tuber reducing sugar contents were much lower, and tuber sucrose contents were much higher, in transgenic than in wild-type tubers stored at 3-9°C for up to eight months. Large differences in VInv mRNA accumulation were not observed at later times in storage, especially at temperatures below 9°C, so differences in invertase activity were likely established early in the storage period and maintained by stability of the invertase protein. Sugar contents, chip color, and expression of several of the studied genes, including AGPase and GBSS, were affected by storage temperature in both wild-type and transgenic tubers. Though transcript accumulation for other sugar-metabolism genes was affected by storage temperature and duration, it was essentially unaffected by invertase silencing and altered sugar contents. Differences in stem- and bud-end sugar contents in wild-type and transgenic tubers suggested different compartmentalization of sucrose at the two ends of stored tubers. VInv silencing significantly reduced cold-induced sweetening in stored potato tubers, likely by means of differential VInv expression early in storage. Transgenic tubers retained sensitivity to storage temperature, and accumulated greater amounts of sucrose, glucose and fructose at 3°C than at 7-9°C. At each storage temperature, suppression of VInv expression and large differences in tuber sugar contents had no effect on expression of AGPase and GBSS, genes involved in starch metabolism, suggesting that transcription of these genes is not regulated by tuber sugar content.

7 CFR 51.2128 - Damage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... materially detracts from the appearance of the individual kernel, or the edible or shipping quality of the... maximum allowed for any one defect shall be considered as damage: (a) Chipped and scratched kernels, when the affected area on an individual kernel aggregates more than the equivalent of a circle one-quarter...

Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects.

PubMed

Lamm, Noa; Ben-David, Uri; Golan-Lev, Tamar; Storchová, Zuzana; Benvenisty, Nissim; Kerem, Batsheva

2016-02-04

Human pluripotent stem cells (hPSCs) frequently acquire chromosomal aberrations such as aneuploidy in culture. These aberrations progressively increase over time and may compromise the properties and clinical utility of the cells. The underlying mechanisms that drive initial genomic instability and its continued progression are largely unknown. Here, we show that aneuploid hPSCs undergo DNA replication stress, resulting in defective chromosome condensation and segregation. Aneuploid hPSCs show altered levels of actin cytoskeletal genes controlled by the transcription factor SRF, and overexpression of SRF rescues impaired chromosome condensation and segregation defects in aneuploid hPSCs. Furthermore, SRF downregulation in diploid hPSCs induces replication stress and perturbed condensation similar to that seen in aneuploid cells. Together, these results suggest that decreased SRF expression induces replicative stress and chromosomal condensation defects that underlie the ongoing chromosomal instability seen in aneuploid hPSCs. A similar mechanism may also operate during initiation of instability in diploid cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Reconstructive Surgery of Auricular Defects: An Overview.

PubMed

Ebrahimi, Ali; Kazemi, Alireza; Rasouli, Hamid Reza; Kazemi, Maryam; Kalantar Motamedi, Mohammad Hosein

2015-11-01

Despite the ongoing advances in surgical procedures and promising progress in bioengineering techniques, auricular reconstruction remains a significant challenge in plastic surgery. There are different causes for acquired auricular defects, including trauma, tumor ablation and burns. The management options for upper, middle and lower third auricular defects are briefly reviewed in the current paper. Original research papers investigating the plastic surgeons, otolaryngologists and maxillofacial surgeons in approaching the complicated issue of auricular reconstruction published from January 1995 to December 2014 were aggregated and used in the current study. Utilizing autologous stem cell populations to treat craniofacial defects is a promising field of ongoing investigations. Studies show that cartilage stem/progenitor cells (CSPCs) are highly chondrogenic and can produce elastic reconstructive material with long-term tissue restoration. Auricular reconstruction surgery is a challenging plastic procedure that requires great expertise and expert knowledge of the various techniques available. Novel techniques in the fields of reconstructive bioengineering and regenerative medicine are promising but further research is required before widespread clinical application.

Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration

PubMed Central

Liu, An-Qi; Hu, Cheng-Hu; Jin, Fang; Zhang, Li-Shu; Xuan, Kun

2018-01-01

Periodontal disease is a widespread disease, which without proper treatment, may lead to tooth loss in adults. Because stem cells from the inflammatory microenvironment created by periodontal disease exhibit impaired regeneration potential even under favorable conditions, it is difficult to obtain satisfactory therapeutic outcomes using traditional treatments, which only focus on the control of inflammation. Therefore, a new stem cell-based therapy known as cell aggregates/cell sheets technology has emerged. This approach provides sufficient numbers of stem cells with high viability for treating the defective site and offers new hope in the field of periodontal regeneration. However, it is not sufficient for regenerating periodontal tissues by delivering cell aggregates/cell sheets to the impaired microenvironment in order to suppress the function of resident cells. In the present review, we summarize some promising bioactive molecules that act as cellular signals, which recreate a favorable microenvironment for tissue regeneration, recruit endogenous cells into the defective site and enhance the viability of exogenous cells. PMID:29597317

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint

PubMed Central

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-01-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted. PMID:28670465

Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint.

PubMed

Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

2017-06-01

A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted.

The modular endoprosthesis for mandibular body replacement. Part 2: finite element analysis of endoprosthesis reconstruction of the mandible.

PubMed

Wong, Raymond C W; Tideman, Henk; Merkx, Matthias A W; Jansen, John; Goh, Suk Ming

2012-12-01

Problems with loosening of the modules for the modular endoprosthesis were encountered in animal studies for mandibular body replacement. We performed a finite element analysis to look at the stress distribution and areas of stress concentration in a human sized mandible. Variations were made to the stem and defect length to look at how the forces changed. The hypothesis was: (1) reconstruction with a modular endoprosthesis did not lead to areas of stress concentration beyond the material strength of cortical bone and titanium alloy; (2) changes in dimensions of the endoprosthesis did not cause a corresponding linear increase to the stresses. The endoprosthesis was modelled to create a male, female part with stems and a connection screw (Case I). The stem length was halved (Case II) and defect length doubled (Case III). Geometric data of a human sized mandible were obtained, a continuity defect created digitally at the right molar area and the models combined. Boundary conditions were set and the model loaded to get a bite force of 300 N at the incisor region. An intact mandible was used as a control. The right side of the reconstructed mandible became less rigid and flexed more. The highest stresses were within the endoprosthesis at two areas of stress concentration: (1) shear stress at the superior surface of the stems close to the junction of the stem and the module body; (2) compressive stresses at the bottom bevel of the dove-tailed connection. The stress distribution for Case I and II did not differ much except for the magnitude which was slightly higher for Case II. There was a tendency for outward bending at the module connection for Case III which potentially might cause loosening of the module connection. Displacements of the mandible were less than 1 mm throughout. The endoprosthesis with its present dimensions would be expected to perform adequately at a bite force of 300 N. An increase in defect length caused a tendency for bending at the stem and the module connection. With a decrease in stem length, there were little differences except a slight increase in magnitude. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Automated, Ultra-Sterile Solid Sample Handling and Analysis on a Chip

NASA Technical Reports Server (NTRS)

Mora, Maria F.; Stockton, Amanda M.; Willis, Peter A.

2013-01-01

There are no existing ultra-sterile lab-on-a-chip systems that can accept solid samples and perform complete chemical analyses without human intervention. The proposed solution is to demonstrate completely automated lab-on-a-chip manipulation of powdered solid samples, followed by on-chip liquid extraction and chemical analysis. This technology utilizes a newly invented glass micro-device for solid manipulation, which mates with existing lab-on-a-chip instrumentation. Devices are fabricated in a Class 10 cleanroom at the JPL MicroDevices Lab, and are plasma-cleaned before and after assembly. Solid samples enter the device through a drilled hole in the top. Existing micro-pumping technology is used to transfer milligrams of powdered sample into an extraction chamber where it is mixed with liquids to extract organic material. Subsequent chemical analysis is performed using portable microchip capillary electrophoresis systems (CE). These instruments have been used for ultra-highly sensitive (parts-per-trillion, pptr) analysis of organic compounds including amines, amino acids, aldehydes, ketones, carboxylic acids, and thiols. Fully autonomous amino acid analyses in liquids were demonstrated; however, to date there have been no reports of completely automated analysis of solid samples on chip. This approach utilizes an existing portable instrument that houses optics, high-voltage power supplies, and solenoids for fully autonomous microfluidic sample processing and CE analysis with laser-induced fluorescence (LIF) detection. Furthermore, the entire system can be sterilized and placed in a cleanroom environment for analyzing samples returned from extraterrestrial targets, if desired. This is an entirely new capability never demonstrated before. The ability to manipulate solid samples, coupled with lab-on-a-chip analysis technology, will enable ultraclean and ultrasensitive end-to-end analysis of samples that is orders of magnitude more sensitive than the ppb goal given in the Science Instruments.

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients

PubMed Central

Garçon, Loïc; Ge, Jingping; Manjunath, Shwetha H.; Mills, Jason A.; Apicella, Marisa; Parikh, Shefali; Sullivan, Lisa M.; Podsakoff, Gregory M.; Gadue, Paul; French, Deborah L.; Mason, Philip J.; Bessler, Monica

2013-01-01

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the “safe harbor” AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells. PMID:23744582

Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.

PubMed

Garçon, Loïc; Ge, Jingping; Manjunath, Shwetha H; Mills, Jason A; Apicella, Marisa; Parikh, Shefali; Sullivan, Lisa M; Podsakoff, Gregory M; Gadue, Paul; French, Deborah L; Mason, Philip J; Bessler, Monica; Weiss, Mitchell J

2013-08-08

Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the "safe harbor" AAVS1 locus alleviated abnormalities in ribosome biogenesis and hematopoiesis. Our studies show that pathological features of DBA are recapitulated by iPSCs, provide a renewable source of cells to model various tissue defects, and demonstrate proof of principle for genetic correction strategies in patient stem cells.

Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs).

PubMed

Matthias, Nadine; Hunt, Samuel D; Wu, Jianbo; Lo, Jonathan; Smith Callahan, Laura A; Li, Yong; Huard, Johnny; Darabi, Radbod

2018-03-01

Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA) muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method. Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding. These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

An on-chip coupled resonator optical waveguide single-photon buffer

PubMed Central

Takesue, Hiroki; Matsuda, Nobuyuki; Kuramochi, Eiichi; Munro, William J.; Notomi, Masaya

2013-01-01

Integrated quantum optical circuits are now seen as one of the most promising approaches with which to realize single-photon quantum information processing. Many of the core elements for such circuits have been realized, including sources, gates and detectors. However, a significant missing function necessary for photonic quantum information processing on-chip is a buffer, where single photons are stored for a short period of time to facilitate circuit synchronization. Here we report an on-chip single-photon buffer based on coupled resonator optical waveguides (CROW) consisting of 400 high-Q photonic crystal line-defect nanocavities. By using the CROW, a pulsed single photon is successfully buffered for 150 ps with 50-ps tunability while maintaining its non-classical properties. Furthermore, we show that our buffer preserves entanglement by storing and retrieving one photon from a time-bin entangled state. This is a significant step towards an all-optical integrated quantum information processor. PMID:24217422

Manufacturability of the X Architecture at the 90-nm technology node

NASA Astrophysics Data System (ADS)

Smayling, Michael C.; Sarma, Robin C.; Nagata, Toshiyuki; Arora, Narain; Duane, Michael P.; Oemardani, Shiany; Shah, Santosh

2004-05-01

In this paper, we discuss the results from a test chip that demonstrate the manufacturability and integration-worthiness of the X Architecture at the 90-nm technology node. We discuss how a collaborative effort between the design and chip making communities used the current generation of mask, lithography, wafer processing, inspection and metrology equipment to create 45 degree wires in typical metal pitches for the upper layers on a 90-nm device in a production environment. Cadence Design Systems created the test structure design and chip validation tools for the project. Canon"s KrF ES3 and ArF AS2 scanners were used for the lithography. Applied Materials used its interconnect fabrication technologies to produce the multilayer copper, low-k interconnect on 300-mm wafers. The results were confirmed for critical dimension and defect levels using Applied Materials" wafer inspection and metrology systems.

Customizing the genome as therapy for the β-hemoglobinopathies

PubMed Central

Canver, Matthew C.

2016-01-01

Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats–based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34+ hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders. PMID:27053533

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

PubMed Central

Mondadori, Carlotta; Mainardi, Valerio Luca; Talò, Giuseppe; Candrian, Christian; Święszkowski, Wojciech

2018-01-01

Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects. PMID:29535776

Microphysiological Systems (Tissue Chips) and their Utility for Rare Disease Research.

PubMed

Low, Lucie A; Tagle, Danilo A

2017-01-01

The scientific and technological development of microphysiological systems (MPS) modeling organs-on-chips, or "tissue chips" (TCs), has progressed rapidly over the past decade. Stem cell research and microfluidic concepts have combined to lead to the development of microphysiological platforms representing an ever-expanding list of different human organ systems. In the context of rare diseases, these bioengineered microfluidics platforms hold promise for modeling of disorders and could prove useful in the screening and efficacy testing of existing therapeutics. Additionally, they have the potential for replacing and refining animal use for new drugs and clinical treatments, or could even act as surrogate human systems for testing of new therapeutics in the future, which could be particularly useful in populations of rare disease sufferers. This chapter will discuss the current state of tissue chip research, and challenges facing the field. Additionally, we will discuss how these devices are being used to model basic cellular and molecular phenotypes of rare diseases, holding promise to provide new tools for understanding of disease pathologies and screening and efficacy testing of potential therapeutics for drug discovery.

Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model.

PubMed

Chang, Chih-Hung; Kuo, Tzong-Fu; Lin, Feng-Huei; Wang, Jyh-Horng; Hsu, Yuan-Ming; Huang, Huei-Ting; Loo, Shiao-Tung; Fang, Hsu-Wei; Liu, Hwa-Chang; Wang, Wen-Chih

2011-12-01

This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor β (TGF-β) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-β-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-β-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-β-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. Copyright © 2011 Orthopaedic Research Society.

A CMOS 0.18 μm 600 MHz clock multiplier PLL and a pseudo-LVDS driver for the high speed data transmission for the ALICE Inner Tracking System front-end chip

NASA Astrophysics Data System (ADS)

Lattuca, A.; Mazza, G.; Aglieri Rinella, G.; Cavicchioli, C.; Chanlek, N.; Collu, A.; Degerli, Y.; Dorokhov, A.; Flouzat, C.; Gajanana, D.; Gao, C.; Guilloux, F.; Hillemanns, H.; Hristozkov, S.; Junique, A.; Keil, M.; Kim, D.; Kofarago, M.; Kugathasan, T.; Kwon, Y.; Mager, M.; Sielewicz, K. Marek; Marin Tobon, C. Augusto; Marras, D.; Martinengo, P.; Mugnier, H.; Musa, L.; Pham, T. Hung; Puggioni, C.; Reidt, F.; Riedler, P.; Rousset, J.; Siddhanta, S.; Snoeys, W.; Song, M.; Usai, G.; Van Hoorne, J. Willem; Yang, P.

2016-01-01

This work presents the 600 MHz clock multiplier PLL and the pseudo-LVDS driver which are two essential components of the Data Transmission Unit (DTU), a fast serial link for the 1.2 Gb/s data transmission of the ALICE inner detector front-end chip (ALPIDE). The PLL multiplies the 40 MHz input clock in order to obtain the 600 MHz and the 200 MHz clock for a fast serializer which works in Double Data Rate mode. The outputs of the serializer feed the pseudo-LVDS driver inputs which transmits the data from the pixel chip to the patch panel with a limited number of signal lines. The driver drives a 5.3 m-6.5 m long differential transmission line by steering a maximum of 5 mA of current at the target speed. To overcome bandwidth limitations coming from the long cables the pre-emphasis can be applied to the output. Currents for the main and pre-emphasis driver can individually be adjusted using on-chip digital-to-analog converters. The circuits will be integrated in the pixel chip and are designed in the same 0.18 μm CMOS technology and will operate from the same 1.8 V supply. Design and test results of both circuits are presented.

A low-cost, manufacturable method for fabricating capillary and optical fiber interconnects for microfluidic devices.

PubMed

Hartmann, Daniel M; Nevill, J Tanner; Pettigrew, Kenneth I; Votaw, Gregory; Kung, Pang-Jen; Crenshaw, Hugh C

2008-04-01

Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels. UV light is manually directed onto the ends of the interconnects using a microscope. UV-curable glue is then allowed to wick to the end of the capillaries, fibers, or wires, where it is cured to form rigid, liquid-tight connections. In a variant of this technique, used with light-guiding capillaries and optical fibers, the UV light is directed into the capillaries or fibers, and the UV-glue is cured by the cone of light emerging from the end of each capillary or fiber. This technique is fully self-aligned, greatly improves both the quality and the manufacturability of the interconnects, and has the potential to enable the fabrication of interconnects in a fully automated fashion. Using these methods, including a semi-automated implementation of the second technique, over 10,000 interconnects have been formed in almost 2000 microfluidic chips made of a variety of rigid materials. The resulting interconnects withstand pressures up to at least 800psi, have unswept volumes estimated to be less than 10 femtoliters, and have dead volumes defined only by the length of the capillary.

Nanofat grafting under a split-thickness skin graft for problematic wound management.

PubMed

Kemaloğlu, Cemal Alper

2016-01-01

Obesity and certain medical disorders make the reconstruction of skin defects challenging. Different kind of procedure can be used for these defect, besides, skin grafting is one of the most common and simplest procedure. Fat grafting and stem cells which are located in the adipose tissue have been commonly used in plastic surgery for regeneration and rejuvenation purposes. To decrease graft failure rate we performed nanofat grafting under an autologous split-thickness skin graft in our patient who had a problematic wound. The case of a 35-year-old female patient with a traumatic skin defect on her left anterior crural region is described herein. After subsequent flap reconstruction, the result was disappointing and the defect size was widened. The defect was treated with combined grafting (nanofat grafting under an autologous split-thickness skin graft). At the 6 months follow-up assessment after combined grafting, the integrity of the skin graft was good with excellent pliability. Combined grafting for problematic wounds seems to be a useful technique for cases requiring reconstruction. The potential existence of stem cells may be responsible for the successful result in our patient.

Application of adipose-derived stem cells on scleral contact lens carrier in an animal model of severe acute alkaline burn.

PubMed

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2014-07-01

To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits.

Application of Adipose-Derived Stem Cells on Scleral Contact Lens Carrier in an Animal Model of Severe Acute Alkaline Burn

PubMed Central

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2015-01-01

Purpose To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. Materials and Methods After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Results Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Conclusion Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits. PMID:24901976

Bubble-free on-chip continuous-flow polymerase chain reaction: concept and application.

PubMed

Wu, Wenming; Kang, Kyung-Tae; Lee, Nae Yoon

2011-06-07

Bubble formation inside a microscale channel is a significant problem in general microfluidic experiments. The problem becomes especially crucial when performing a polymerase chain reaction (PCR) on a chip which is subject to repetitive temperature changes. In this paper, we propose a bubble-free sample injection scheme applicable for continuous-flow PCR inside a glass/PDMS hybrid microfluidic chip, and attempt to provide a theoretical basis concerning bubble formation and elimination. Highly viscous paraffin oil plugs are employed in both the anterior and posterior ends of a sample plug, completely encapsulating the sample and eliminating possible nucleation sites for bubbles. In this way, internal channel pressure is increased, and vaporization of the sample is prevented, suppressing bubble formation. Use of an oil plug in the posterior end of the sample plug aids in maintaining a stable flow of a sample at a constant rate inside a heated microchannel throughout the entire reaction, as compared to using an air plug. By adopting the proposed sample injection scheme, we demonstrate various practical applications. On-chip continuous-flow PCR is performed employing genomic DNA extracted from a clinical single hair root sample, and its D1S80 locus is successfully amplified. Also, chip reusability is assessed using a plasmid vector. A single chip is used up to 10 times repeatedly without being destroyed, maintaining almost equal intensities of the resulting amplicons after each run, ensuring the reliability and reproducibility of the proposed sample injection scheme. In addition, the use of a commercially-available and highly cost-effective hot plate as a potential candidate for the heating source is investigated.

Properties of medium-density fiberboard related to hardwood specific gravity

Treesearch

George E. Woodson

1976-01-01

Boards of acceptable quality were made from barky material, pressure-refined from 14 species of southern hardwoods. Static bending and tensile properties (parallel to surface) of specimens were negatively correlated to stem specific gravity (wood plus bark), chip bulk density, and fiber bulk density. Bending and tensile properties increased with increasing...

A microfluidic chip containing multiple 3D nanofibrous scaffolds for culturing human pluripotent stem cells

NASA Astrophysics Data System (ADS)

Wertheim, Lior; Shapira, Assaf; Amir, Roey J.; Dvir, Tal

2018-04-01

In microfluidics-based lab-on-a-chip systems, which are used for investigating the effect of drugs and growth factors on cells, the latter are usually cultured within the device’s channels in two-dimensional, and not in their optimal three-dimensional (3D) microenvironment. Herein, we address this shortfall by designing a microfluidic system, comprised of two layers. The upper layer of the system consists of multiple channels generating a gradient of soluble factors. The lower layer is comprised of multiple wells, each deposited with 3D, nanofibrous scaffold. We first used a mathematical model to characterize the fluid flow within the system. We then show that induced pluripotent stem cells can be seeded within the 3D scaffolds and be exposed to a well-mixed gradient of soluble factors. We believe that utilizing such system may enable in the future to identify new differentiation factors, investigate drug toxicity, and eventually allow to perform analyses on patient-specific tissues, in order to fit the appropriate combination and concentration of drugs.

In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins

PubMed Central

Pakdaman, Yasaman; Sanchez-Guixé, Monica; Kleppe, Rune; Erdal, Sigrid; Bustad, Helene J.; Bjørkhaug, Lise; Haugarvoll, Kristoffer; Tzoulis, Charalampos; Heimdal, Ketil; Knappskog, Per M.; Johansson, Stefan

2017-01-01

Spinocerebellar ataxia, autosomal recessive 16 (SCAR16) is caused by biallelic mutations in the STIP1 homology and U-box containing protein 1 (STUB1) gene encoding the ubiquitin E3 ligase and dimeric co-chaperone C-terminus of Hsc70-interacting protein (CHIP). It has been proposed that the disease mechanism is related to CHIP’s impaired E3 ubiquitin ligase properties and/or interaction with its chaperones. However, there is limited knowledge on how these mutations affect the stability, folding, and protein structure of CHIP itself. To gain further insight, six previously reported pathogenic STUB1 variants (E28K, N65S, K145Q, M211I, S236T, and T246M) were expressed as recombinant proteins and studied using limited proteolysis, size-exclusion chromatography (SEC), and circular dichroism (CD). Our results reveal that N65S shows increased CHIP dimerization, higher levels of α-helical content, and decreased degradation rate compared with wild-type (WT) CHIP. By contrast, T246M demonstrates a strong tendency for aggregation, a more flexible protein structure, decreased levels of α-helical structures, and increased degradation rate compared with WT CHIP. E28K, K145Q, M211I, and S236T also show defects on structural properties compared with WT CHIP, although less profound than what observed for N65S and T246M. In conclusion, our results illustrate that some STUB1 mutations known to cause recessive SCAR16 have a profound impact on the protein structure, stability, and ability of CHIP to dimerize in vitro. These results add to the growing understanding on the mechanisms behind the disorder. PMID:28396517

The use of small (2.7 mm) screws for arthroscopically guided repair of carpal chip fractures.

PubMed

Wright, I M; Smith, M R W

2011-05-01

Removal of large chip fractures of the carpal bones and the osteochondral deficits that result, have been associated with a worse prognosis than removal of small fragments in similar locations. Reducing the articular defects by repair of large osteochondral fragments may have advantages over removal. Horses with osteochondral chip fractures that were of sufficient size and infrastructure to be repaired with small (2.7 mm diameter) AO/ASIF cortex screws were identified and repair effected by arthroscopically guided internal fixation. Thirty-three horses underwent surgery to repair 35 fractures of the dorsodistal radial carpal bone (n = 25), the dorsal margin of the radial facet of the third carpal bone (n = 9) and the intermediate facet of the distal radius (n = 1). There were no surgical complications and fractures healed satisfactorily in 26 of 28 horses and 23 horses returned to racing performance. Arthroscopically guided repair of carpal chip fractures with small diameter cortex screws is technically feasible and experiences with 33 cases suggest that this may have advantages over fragment removal in managing such cases. Surgeons treating horses with large chip fractures of the carpal bones should consider arthroscopically guided internal fixation as an alternative to removal. © 2010 EVJ Ltd.

Bone Repair Cells for Craniofacial Regeneration

PubMed Central

Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

2012-01-01

Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

Auricular Cartilage Regeneration with Adipose-Derived Stem Cells in Rabbits

PubMed Central

Park, Hee-Young; Choi, Kyung-Un; Kim, Sung-Dong; Kong, Soo-Keun

2018-01-01

Tissue engineering cell-based therapy using induced pluripotent stem cells and adipose-derived stem cells (ASCs) may be promising tools for therapeutic applications in tissue engineering because of their abundance, relatively easy harvesting, and high proliferation potential. The purpose of this study was to investigate whether ASCs can promote the auricular cartilage regeneration in the rabbit. In order to assess their differentiation ability, ASCs were injected into the midportion of a surgically created auricular cartilage defect in the rabbit. Control group was injected with normal saline. After 1 month, the resected auricles were examined histopathologically and immunohistochemically. The expression of collagen type II and transforming growth factor-β1 (TGF-β1) were analyzed by quantitative polymerase chain reaction. Histopathology showed islands of new cartilage formation at the site of the surgically induced defect in the ASC group. Furthermore, Masson's trichrome staining and immunohistochemistry for S-100 showed numerous positive chondroblasts. The expression of collagen type II and TGF-β1 were significantly higher in the ASCs than in the control group. In conclusion, ASCs have regenerative effects on the auricular cartilage defect of the rabbit. These effects would be expected to contribute significantly to the regeneration of damaged cartilage tissue in vivo. PMID:29743810

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

Micro flow-through PCR in a PMMA chip fabricated by KrF excimer laser.

PubMed

Yao, Liying; Liu, Baoan; Chen, Tao; Liu, Shibing; Zuo, Tiechuan

2005-09-01

As the third PCR technology, micro flow-through PCR chip can amplify DNA specifically in an exponential fashion in vitro. Nowadays many academies in the world have successfully amplified DNA using their own-made flow-through PCR chip. In this paper, the ablation principle of PMMA at 248 nm excimer laser was studied, then a PMMA based flow-through PCR chip with 20 cycles was fabricated by excimer laser at 19 kv and 18 mm/min. The chip was bonded together with another cover chip at 105( composite function)C, 160 N and 20 minutes. In the end, it was integrated with electrical thermal thin films and Pt 100 temperature sensors. The temperature controllers was built standard PID digital temperature controller, the temperature control precision was +/- 0.2( composite function)C. The temperature grads between the three temperature zones were 16.5 and 22.2( composite function)C respectively, the gaps between the temperature zones could realize heat insulation.

Use of Adipose Derived Stem Cells to Treat Large Bone Defects. Addendum

DTIC Science & Technology

2009-07-01

optimal delivery . We have also completed characterization of our segmental defect model, including analysis of vascular ingrowth during defect healing...cells seeded in 1.2% Keltone alginate at a density of 12-15x106cells/ml were loaded on 24-well transwell insert membranes [6]. Once hydrogel discs...process from tissue culture plates and hydrogels does not alter the surface phenotype. Gene expression of surface markers and proteins associated with

Dry-film polymer waveguide for silicon photonics chip packaging.

PubMed

Hsu, Hsiang-Han; Nakagawa, Shigeru

2014-09-22

Polymer waveguide made by dry film process is demonstrated for silicon photonics chip packaging. With 8 μm × 11.5 μm core waveguide, little penalty is observed up to 25 Gbps before or after the light propagate through a 10-km long single-mode fiber (SMF). Coupling loss to SMF is 0.24 dB and 1.31 dB at the polymer waveguide input and output ends, respectively. Alignment tolerance for 0.5 dB loss increase is +/- 1.0 μm along both vertical and horizontal directions for the coupling from the polymer waveguide to SMF. The dry-film polymer waveguide demonstrates promising performance for silicon photonics chip packaging used in next generation optical multi-chip module.

The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function.

PubMed

Gu, Yue; Jones, Amanda E; Yang, Wei; Liu, Shanrun; Dai, Qian; Liu, Yudong; Swindle, C Scott; Zhou, Dewang; Zhang, Zhuo; Ryan, Thomas M; Townes, Tim M; Klug, Christopher A; Chen, Dongquan; Wang, Hengbin

2016-01-05

Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitination (ubH2A) level and regulates hematopoiesis in vivo. Here we investigated the function of Usp16 in mouse hematopoiesis. Conditional deletion of Usp16 in bone marrow resulted in a significant increase of global ubH2A level and lethality. Usp16 deletion did not change HSC number but was associated with a dramatic reduction of mature and progenitor cell populations, revealing a role in governing HSC lineage commitment. ChIP- and RNA-sequencing studies in HSC and progenitor cells revealed that Usp16 bound to many important hematopoietic regulators and that Usp16 deletion altered the expression of genes in transcription/chromosome organization, immune response, hematopoietic/lymphoid organ development, and myeloid/leukocyte differentiation. The altered gene expression was partly rescued by knockdown of PRC1 subunits, suggesting that Usp16 and PRC1 counterbalance each other to regulate cellular ubH2A level and gene expression in the hematopoietic system. We further discovered that knocking down Cdkn1a (p21cip1), a Usp16 target and regulated gene, rescued the altered cell cycle profile and differentiation defect of Usp16-deleted HSCs. Collectively, these studies identified Usp16 as one of the histone H2A deubiquitinases, which coordinates with the H2A ubiquitin ligase PRC1 to regulate hematopoiesis, and revealed cell cycle regulation by Usp16 as key for HSC differentiation.

Electromigration and thermomigration in lead-free tin-silver-copper and eutectic tin-lead flip chip solder joints

NASA Astrophysics Data System (ADS)

Ou Yang, Fan-Yi

Phase separation and microstructure change of eutectic SnPb and SnAgCu flip chip solder joint were investigated under thermomigration, electromigration, stressmigration and the combination of these effects. Different morphological behaviors under DC and AC electromigration were seen. Phase separation with Pb rich phase migration to the anode was observed when current density is below 1.6 x 104 A/cm2 at 100°C. For some cases, phase separation of Pb-rich phase and Su-rich phase as well as refinement of lamellar microstructure has also been observed. We propose that the refinement is due to recrystallization. On the other hand, time-dependent melting of eutectic SnPb flip chip solder joints has been observed to occur frequently with current density above 1.6 x 104 A/cm 2at 100°C. It has been found that it is due to joule heating of the on-chip Al interconnects. We found that electromigration has especially generated voids at the anode of the Al. This damage has greatly increased the resistance of the Al, which produces the heat needed to melt the solder joint. Owing to the line-to-bump configuration in flip chip solder joints, current crowding occurs when electrons enters into or exits from the solder bump. At the cathode contact, current crowding induced pancake-type void formation was observed widely. Furthermore, at the anode contact, we note that hillock or whisker forms. The cross-sectioned surface in SnPb showed dimple and bulge after electromigration, while that of SnAgCu remained flat. The difference is due to a larger back stress in the SnAgCu, consequently electromigration in SnAgCu is slower than that in SnPb. For thermomigration in eutectic SnPb flip chip solder joints, phase separation of Sn and Pb occurred, with Pb moving to the cold end. Both Sn and Pb have a stepwise concentration profile across solder bump. Refinement of lamellar microstructure was observed, indicating recrystallization. Also, thermomigration in eutectic SnAgCu flip chip solder joint were presented. It seems that vacancy flux plays a dominant role in thermomigration in Pb-free solder bumps; voids formed on the cold end and Sn moved to the hot end.

Fabrication and characterization of on-chip optical nonlinear chalcogenide nanofiber devices.

PubMed

Zhang, Qiming; Li, Ming; Hao, Qiang; Deng, Dinghuan; Zhou, Hui; Zeng, Heping; Zhan, Li; Wu, Xiang; Liu, Liying; Xu, Lei

2010-11-15

Chalcogenide (As(2)S(3)) nanofibers as narrow as 200 nm in diameter are drawn by the fiber pulling method, are successfully embedded in SU8 polymer, and form on-chip waveguides and high-Q microknot resonators (Q = 3.9 × 10(4)) with smooth cleaved end faces. Resonance tuning of resonators is realized by localized laser irradiation. Strong supercontinuum generation with a bandwidth of 500 nm is achieved in a 7-cm-long on-chip chalcogenide waveguide. Our result provides a method for the development of compact, high-optical-quality, and robust photonic devices.

Human unrestricted somatic stem cells loaded in nanofibrous PCL scaffold and their healing effect on skin defects.

PubMed

Bahrami, Hoda; Keshel, Saeed Heidari; Chari, Aliakbar Jafari; Biazar, Esmaeil

2016-09-01

Unrestricted somatic stem cells (USSCs) loaded in nanofibrous polycaprolactone (PCL) scaffolds can be used for skin regeneration when grafted onto full-thickness skin defects of rats. Nanofibrous PCL scaffolds were designed by the electrospinning method and crosslinked with laminin protein. Afterwards, the scaffolds were evaluated by scanning electron microscopy, and physical and mechanical assays. In this study, nanofibrous PCL scaffolds loaded with USSCs were grafted onto the skin defects. The wounds were subsequently investigated 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; study samples exhibited the most pronounced effect on wound closure, with statistically significant improvement in wound healing being seen at 21 days post-operatively. Histological examinations of healed wounds from all samples showed a thin epidermis plus recovered skin appendages in the dermal layer for samples with cell. Thus, the graft of nanofibrous PCL scaffolds loaded with USSC showed better results during the healing process of skin defects in rat models.

Influence of stand density on stem quality in pole-size northern hardwoods.

Treesearch

Richard M. Godman; David J. Books

1971-01-01

Relates the type and frequency of limbs and limb-related defects in the first two logs of five hardwood species to residual basal area 15 years after initial cutting. Also discusses other tree characteristics influenced by stand density and the applicability of present silvicultural guides to improve stem quality.

A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits.

PubMed

Dashtdar, Havva; Rothan, Hussin A; Tay, Terence; Ahmad, Raja Elina; Ali, Razif; Tay, Liang Xin; Chong, Pan Pan; Kamarul, Tunku

2011-09-01

Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p < 0.05). Quantitative analysis of GAGs was consistent with these results. Histological and immunohistochemical analysis demonstrated hyaline-like cartilage regeneration in the transplanted sites. Significant differences between the histological scores based on O'Driscoll histological grading were observed between contralateral knees at both 3 and 6 months (p < 0.05). No significant differences were observed between the Britberg, O'Driscoll scores, and GAGs/total protein content when comparing defect sites treated with MSC and CMSC (p > 0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes. Copyright © 2011 Orthopaedic Research Society.

Harnessing extracellular vesicles to direct endochondral repair of large bone defects

PubMed Central

Ferreira, E.

2018-01-01

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006. PMID:29922444

The C-stem in clinical practice: fifteen-year follow-up of a triple tapered polished cemented stem.

PubMed

Purbach, Bodo; Kay, Peter R; Siney, Paul D; Fleming, Patricia A; Wroblewski, B Michael

2013-09-01

The triple tapered polished cemented stem, C-Stem, introduced in 1993 was based on the original Charnley concept of the "flat back" polished stem. We present our continuing experience with the C-Stem in 621 consecutive primary arthroplasties implanted into 575 patients between 1993 and 1997. Four hundred and eighteen arthroplasties had a clinical and radiological follow-up past 10 years with a mean follow-up of 13 years (10-15). There were no revisions for stem loosening but 2 stems were revised for fracture - both with a defective cement mantle proximally. The stem design and the surgical technique support the original Charnley concept of limited stem subsidence within the cement mantle and the encouraging results continue to stand as a credit to Sir John Charnley's original philosophy. Copyright © 2013 Elsevier Inc. All rights reserved.

Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial.

PubMed

Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min; Zhang, Xi-Yu; Zhang, Yong-Jie; Dong, Guang-Ying; Lu, Hong; Chu, Qing; Xu, Jie; Yu, Yang; Wu, Rui-Xin; Yin, Yuan; Shi, Songtao; Jin, Yan

2016-02-19

Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05). This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size. NCT01357785 Date registered: 18 May 2011.

Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair.

PubMed

Dupont, Kenneth M; Boerckel, Joel D; Stevens, Hazel Y; Diab, Tamim; Kolambkar, Yash M; Takahata, Masahiko; Schwarz, Edward M; Guldberg, Robert E

2012-03-01

Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.

Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects.

PubMed

Oliveira, João T; Gardel, Leandro S; Rada, Tommaso; Martins, Luís; Gomes, Manuela E; Reis, Rui L

2010-09-01

In this work, the ability of gellan gum hydrogels coupled with autologous cells to regenerate rabbit full-thickness articular cartilage defects was tested. Five study groups were defined: (a) gellan gum with encapsulated chondrogenic predifferentiated rabbit adipose stem cells (ASC + GF); (b) gellan gum with encapsulated nonchondrogenic predifferentiated rabbit adipose stem cells (ASC); (c) gellan gum with encapsulated rabbit articular chondrocytes (AC) (standard control); (d) gellan gum alone (control); (e) empty defect (control). Full-thickness articular cartilage defects were created and the gellan gum constructs were injected and left for 8 weeks. The macroscopic aspect of the explants showed a progressive increase of similarity with the lateral native cartilage, stable integration at the defect site, more pronouncedly in the cell-loaded constructs. Tissue scoring showed that ASC + GF exhibited the best results regarding tissue quality progression. Alcian blue retrieved similar results with a better outcome for the cell-loaded constructs. Regarding real-time PCR analyses, ASC + GF had the best progression with an upregulation of collagen type II and aggrecan, and a downregulation of collagen type I. Gellan gum hydrogels combined with autologous cells constitute a promising approach for the treatment of articular cartilage defects, and adipose derived cells may constitute a valid alternative to currently used articular chondrocytes. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Histone H3K9 Trimethylase Eggless Controls Germline Stem Cell Maintenance and Differentiation

PubMed Central

Zhou, Jian; McDowell, William; Park, Jungeun; Haug, Jeff; Staehling, Karen; Tang, Hong; Xie, Ting

2011-01-01

Epigenetic regulation plays critical roles in the regulation of cell proliferation, fate determination, and survival. It has been shown to control self-renewal and lineage differentiation of embryonic stem cells. However, epigenetic regulation of adult stem cell function remains poorly defined. Drosophila ovarian germline stem cells (GSCs) are a productive adult stem cell system for revealing regulatory mechanisms controlling self-renewal and differentiation. In this study, we show that Eggless (Egg), a H3K9 methyltransferase in Drosophila, is required in GSCs for controlling self-renewal and in escort cells for regulating germ cell differentiation. egg mutant ovaries primarily exhibit germ cell differentiation defects in young females and gradually lose GSCs with time, indicating that Egg regulates both germ cell maintenance and differentiation. Marked mutant egg GSCs lack expression of trimethylated H3K9 (H3k9me3) and are rapidly lost from the niche, but their mutant progeny can still differentiate into 16-cell cysts, indicating that Egg is required intrinsically to control GSC self-renewal but not differentiation. Interestingly, BMP-mediated transcriptional repression of differentiation factor bam in marked egg mutant GSCs remains normal, indicating that Egg is dispensable for BMP signaling in GSCs. Normally, Bam and Bgcn interact with each other to promote GSC differentiation. Interestingly, marked double mutant egg bgcn GSCs are still lost, but their progeny are able to differentiate into 16-cell cysts though bgcn mutant GSCs normally do not differentiate, indicating that Egg intrinsically controls GSC self-renewal through repressing a Bam/Bgcn-independent pathway. Surprisingly, RNAi-mediated egg knockdown in escort cells leads to their gradual loss and a germ cell differentiation defect. The germ cell differentiation defect is at least in part attributed to an increase in BMP signaling in the germ cell differentiation niche. Therefore, this study has revealed the essential roles of histone H3K9 trimethylation in controlling stem cell maintenance and differentiation through distinct mechanisms. PMID:22216012

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2015-10-01

Fracture, Mesenchymal Stem Cells , Paracrine Review Article Hylonome The authors have no conflict of interest. Corresponding author: Melissa Kacena...Cowin AJ, Kaur P. Pericytes, mesenchymal stem cells and the wound healing process. Cells 2013;2:621-34. 17. Kumar A, Salimath BP, Stark GB, Finkenzeller G... Cell Mater 2009;18:96-111. 39. Gao X, Usas A, Tang Y, et al. A comparison of bone re- generation with human mesenchymal stem cells and mus- cle

Crossbar Nanocomputer Development

DTIC Science & Technology

2012-04-01

their utilization. Areas such as neuromorphic computing, signal processing, arithmetic processing, and crossbar computing are only some of the...due to its intrinsic, network-on- chip flexibility to re-route around defects. Preliminary efforts in crossbar computing have been demonstrated by...they approach their scaling limits [2]. Other applications that memristive devices are suited for include FPGA [3], encryption [4], and neuromorphic

Optimization of manufacturing of emitter-coupled logic to decrease surface of chip

NASA Astrophysics Data System (ADS)

Pankratov, E. L.; Bulaeva, E. A.

2015-11-01

In this paper, we introduce an approach to increase integration rate of bipolar heterotransistors. The approach based on doping of required parts of heterostructure by diffusion or implantation and optimization of annealing of dopant and/or radiation defects. As simplification of the considered approach to increase integration rate we consider possibility to used common collector.

Aerial imaging technology for photomask qualification: from a microscope to a metrology tool

NASA Astrophysics Data System (ADS)

Garetto, Anthony; Scherübl, Thomas; Peters, Jan Hendrik

2012-09-01

Photomasks carry the structured information of the chip designs printed with lithography scanners onto wafers. These structures, for the most modern technologies, are enlarged by a factor of 4 with respect to the final circuit design, and 20-60 of these photomasks are needed for the production of a single completed chip used, for example, in computers or cell phones. Lately, designs have been reported to be on the drawing board with close to 100 of these layers. Each of these photomasks will be reproduced onto the wafer several hundred times and typically 5000-50 000 wafers will be produced with each of them. Hence, the photomasks need to be absolutely defect-free to avoid any fatal electrical shortcut in the design or drastic performance degradation. One well-known method in the semiconductor industry is to analyze the aerial image of the photomask in a dedicated tool referred to as Aerial Imaging Measurement System, which emulates the behavior of the respective lithography scanner used for the imaging of the mask. High-end lithography scanners use light with a wavelength of 193 nm and high numerical apertures (NAs) of 1.35 utilizing a water film between the last lens and the resist to be illuminated (immersion scanners). Complex illumination shapes enable the imaging of structures well below the wavelength used. Future lithography scanners will work at a wavelength of 13.5 nm [extreme ultraviolet (EUV)] and require the optical system to work with mirrors in vacuum instead of the classical lenses used in current systems. The exact behavior of these systems is emulated by the Aerial Image Measurement System (AIMS™; a Trademark of Carl Zeiss). With these systems, any position of the photomask can be imaged under the same illumination condition used by the scanners, and hence, a prediction of the printing behavior of any structure can be derived. This system is used by mask manufacturers in their process flow to review critical defects or verify defect repair success. In this paper, we give a short introduction into the lithography roadmap driving the development cycles of the AIMS systems focusing primarily on the complexity of the structures to be reviewed. Second, we describe the basic principle of the AIMS technology and how it is used. The last section is dedicated to the development of the latest generation of the AIMS for EUV, which is cofinanced by several semiconductor companies in order to close a major gap in the mask manufacturing infrastructure and the challenges to be met.

Morphological characteristics of loblolly pine wood as related to specific gravity, growth rate and distance from pith

Treesearch

Charles W. McMillin

1968-01-01

Earlywood and latewood tracheid length and transverse cellular dimensions of wood removed from stems of loblolly pine (Pinus taeda L.) and factorially aegregated by specific gravity, rings from the pith, and growth rate were determined from sample chips. The independent relationships of each factor with fiber morphology are described.

Analysis on storage off-gas emissions from woody, herbaceous, and torrefied biomass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tumuluru, Jaya Shankar; Lim, C. Jim; Bi, Xiaotao T.

Wood chips, torrefied wood chips, ground switchgrass, and wood pellets were tested for off-gas emissions during storage. Storage canisters with gas-collection ports were used to conduct experiments at room temperature of 20 °C and in a laboratory oven set at 40 °C. Commercially-produced wood pellets yielded the highest carbon monoxide (CO) emissions at both 20 and 40 °C (1600 and 13,000 ppmv), whereas torrefied wood chips emitted the lowest of about <200 and <2000 ppmv. Carbon dioxide (CO₂) emissions from wood pellets were 3000 ppmv and 42,000 ppmv, whereas torrefied wood chips registered at about 2000 and 25,000 ppmv, atmore » 20 and 40 °C at the end of 11 days of storage. CO emission factors (milligrams per kilogram of biomass) calculated were lowest for ground switchgrass and torrefied wood chips (2.68 and 4.86 mg/kg) whereas wood pellets had the highest CO of about 10.60 mg/kg, respectively, at 40 °C after 11 days of storage. In the case of CO₂, wood pellets recorded the lowest value of 55.46 mg/kg, whereas switchgrass recorded the highest value of 318.72 mg/kg. This study concludes that CO emission factor is highest for wood pellets, CO₂ is highest for switchgrass and CH₄ is negligible for all feedstocks except for wood pellets, which is about 0.374 mg/kg at the end of 11-day storage at 40 °C.« less

Analysis on storage off-gas emissions from woody, herbaceous, and torrefied biomass

DOE PAGES

Tumuluru, Jaya Shankar; Lim, C. Jim; Bi, Xiaotao T.; ...

2015-03-02

Wood chips, torrefied wood chips, ground switchgrass, and wood pellets were tested for off-gas emissions during storage. Storage canisters with gas-collection ports were used to conduct experiments at room temperature of 20 °C and in a laboratory oven set at 40 °C. Commercially-produced wood pellets yielded the highest carbon monoxide (CO) emissions at both 20 and 40 °C (1600 and 13,000 ppmv), whereas torrefied wood chips emitted the lowest of about <200 and <2000 ppmv. Carbon dioxide (CO₂) emissions from wood pellets were 3000 ppmv and 42,000 ppmv, whereas torrefied wood chips registered at about 2000 and 25,000 ppmv, atmore » 20 and 40 °C at the end of 11 days of storage. CO emission factors (milligrams per kilogram of biomass) calculated were lowest for ground switchgrass and torrefied wood chips (2.68 and 4.86 mg/kg) whereas wood pellets had the highest CO of about 10.60 mg/kg, respectively, at 40 °C after 11 days of storage. In the case of CO₂, wood pellets recorded the lowest value of 55.46 mg/kg, whereas switchgrass recorded the highest value of 318.72 mg/kg. This study concludes that CO emission factor is highest for wood pellets, CO₂ is highest for switchgrass and CH₄ is negligible for all feedstocks except for wood pellets, which is about 0.374 mg/kg at the end of 11-day storage at 40 °C.« less

A 0.5 cm(3) four-channel 1.1 mW wireless biosignal interface with 20 m range.

PubMed

Morrison, Tim; Nagaraju, Manohar; Winslow, Brent; Bernard, Amy; Otis, Brian P

2014-02-01

This paper presents a self-contained, single-chip biosignal monitoring system with wireless programmability and telemetry interface suitable for mainstream healthcare applications. The system consists of low-noise front end amplifiers, ADC, MICS/ISM transmitter and infrared programming capability to configure the state of the chip. An on-chip packetizer ensures easy pairing with standard off-the-shelf receivers. The chip is realized in the IBM 130 nm CMOS process with an area of 2×2 mm(2). The entire system consumes 1.07 mW from a 1.2 V supply. It weighs 0.6 g including a zinc-air battery. The system has been extensively tested in in vivo biological experiments and requires minimal human interaction or calibration.

A 2- to 7-Year Follow-Up of a Modular Iliac Screw Cup in Major Acetabular Defects: Clinical, Radiographic and Survivorship Analysis With Comparison to the Literature.

PubMed

Cadossi, Matteo; Garcia, Flávio Luís; Sambri, Andrea; Andreoli, Isabella; Dallari, Dante; Pignatti, Giovanni

2017-01-01

Inadequate acetabular bone stock is a major issue in total hip arthroplasty, and several treatment options are available. Stemmed cups have been used in this scenario with variable results. A novel modular polyaxial uncemented iliac screw cup (HERM-BS-Sansone cup-Citieffe s.r.l., Calderara di Reno, Bologna, Italy) has been recently introduced to overcome the drawbacks of stemmed cups. In this retrospective study, we report the results of this cup in patients with large acetabular bone defects at 2- to 7-year follow-up. We evaluated a consecutive series of 121 hips (118 revisions and 3 complex primary arthroplasties) treated with this novel cup at a mean follow-up of 46 months. Kaplan-Meier survival analysis was performed with implant revision for any reason as a primary end point. Further survival analysis was performed excluding septic failures. Clinical outcome was assessed with the Harris Hip Score. There had been 7 reoperations: 1 for aseptic loosening, 5 for deep infection, and 1 for recurrent dislocation. In 5 cases, the cup was removed; estimated survival rate at 5-year follow-up with implant removal for any reason was 95.6% (95% confidence interval = 91-99), and 98.3% (95% CI = 96-100) excluding those failed for infection. Mean Harris Hip Score at latest follow-up was 77 points (range, 44-95; standard deviation = 11.9). The present findings show the short-term efficacy of the iliac screw cup with respect to implant survival. A longer follow-up and a larger number of patients are necessary to confirm the encouraging preliminary results. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies on Auditory and Vestibular End Organs and Brain Stem Nuclei. [inner ear damage and hearing defects

NASA Technical Reports Server (NTRS)

Ades, H. W.

1974-01-01

Cats were exposed to tones of 125, 1000, 2000, and 4000 Hz at sound pressure levels in the range 120 to 157.5 db, and for durations of one hour (1000, 2000, 4000 Hz) or four hours (125 Hz). Pure tone audiograms were obtained for each animal before and after exposure. Cochleas of animals were examined by phase-contrast microscopy. Extent of inner ear damage and range of frequencies for which hearing loss occurred increased as exposure tone was decreased in frequency. For example, exposure to 4000 Hz produced damage in a restricted region of the cochlea and hearing loss for a relatively narrow range of frequencies; exposure to 125 Hz produced wide-spread inner ear damage and hearing loss throughout the frequency range 125 to 6000 Hz.

Customizing the genome as therapy for the β-hemoglobinopathies.

PubMed

Canver, Matthew C; Orkin, Stuart H

2016-05-26

Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats-based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34(+) hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders. © 2016 by The American Society of Hematology.

Determination of Specific Forces and Tool Deflections in Micro-milling of Ti-6Al-4V alloy using Finite Element Simulations and Analysis

NASA Astrophysics Data System (ADS)

Farina, Simone; Thepsonti, Thanongsak; Ceretti, Elisabetta; Özel, Tugrul

2011-05-01

Titanium alloys offer superb properties in strength, corrosion resistance and biocompatibility and are commonly utilized in medical devices and implants. Micro-end milling process is a direct and rapid fabrication method for manufacturing medical devices and implants in titanium alloys. Process performance and quality depend upon an understanding of the relationship between cutting parameters and forces and resultant tool deflections to avoid tool breakage. For this purpose, FE simulations of chip formation during micro-end milling of Ti-6Al-4V alloy with an ultra-fine grain solid carbide two-flute micro-end mill are investigated using DEFORM software. At first, specific forces in tangential and radial directions of cutting during micro-end milling for varying feed advance and rotational speeds have been determined using designed FE simulations for chip formation process. Later, these forces are applied to the micro-end mill geometry along the axial depth of cut in 3D analysis of ABAQUS. Consequently, 3D distributions for tool deflections & von Misses stress are determined. These analyses will yield in establishing integrated multi-physics process models for high performance micro-end milling and a leap-forward to process improvements.

Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koshi; Murono, Shigeyuki; Omori, Koichi

2017-07-01

Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Navigating tissue chips from development to dissemination: A pharmaceutical industry perspective

PubMed Central

Fabre, Kristin; Chakilam, Ananthsrinivas; Dragan, Yvonne; Duignan, David B; Eswaraka, Jeetu; Gan, Jinping; Guzzie-Peck, Peggy; Otieno, Monicah; Jeong, Claire G; Keller, Douglas A; de Morais, Sonia M; Phillips, Jonathan A; Proctor, William; Sura, Radhakrishna; Van Vleet, Terry; Watson, David; Will, Yvonne; Tagle, Danilo; Berridge, Brian

2017-01-01

Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery. Despite the tremendous science and innovation invested in these tissue chips, significant challenges remain to be addressed to enable their routine adoption into the industrial laboratory. This article describes the main steps that need to be taken and highlights key considerations in order to transform tissue chip technology from the hands of the innovators into those of the industrial scientists. Written by scientists from 13 pharmaceutical companies and partners at the National Institutes of Health, this article uniquely captures a consensus view on the progression strategy to facilitate and accelerate the adoption of this valuable technology. It concludes that success will be delivered by a partnership approach as well as a deep understanding of the context within which these chips will actually be used. Impact statement The rapid pace of scientific innovation in the tissue chip (TC) field requires a cohesive partnership between innovators and end users. Near term uptake of these human-relevant platforms will fill gaps in current capabilities for assessing important properties of disposition, efficacy and safety liabilities. Similarly, these platforms could support mechanistic studies which aim to resolve challenges later in development (e.g. assessing the human relevance of a liability identified in animal studies). Building confidence that novel capabilities of TCs can address real world challenges while they themselves are being developed will accelerate their application in the discovery and development of innovative medicines. This article outlines a strategic roadmap to unite innovators and end users thus making implementation smooth and rapid. With the collective contributions from multiple international pharmaceutical companies and partners at National Institutes of Health, this article should serve as an invaluable resource to the multi-disciplinary field of TC development. PMID:28622731

Navigating tissue chips from development to dissemination: A pharmaceutical industry perspective.

PubMed

Ewart, Lorna; Fabre, Kristin; Chakilam, Ananthsrinivas; Dragan, Yvonne; Duignan, David B; Eswaraka, Jeetu; Gan, Jinping; Guzzie-Peck, Peggy; Otieno, Monicah; Jeong, Claire G; Keller, Douglas A; de Morais, Sonia M; Phillips, Jonathan A; Proctor, William; Sura, Radhakrishna; Van Vleet, Terry; Watson, David; Will, Yvonne; Tagle, Danilo; Berridge, Brian

2017-10-01

Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these chips have the potential to increase the predictive power of preclinical modeling, which in turn will move the pharmaceutical industry closer to its aspiration of clinically relevant and ultimately animal-free drug discovery. Despite the tremendous science and innovation invested in these tissue chips, significant challenges remain to be addressed to enable their routine adoption into the industrial laboratory. This article describes the main steps that need to be taken and highlights key considerations in order to transform tissue chip technology from the hands of the innovators into those of the industrial scientists. Written by scientists from 13 pharmaceutical companies and partners at the National Institutes of Health, this article uniquely captures a consensus view on the progression strategy to facilitate and accelerate the adoption of this valuable technology. It concludes that success will be delivered by a partnership approach as well as a deep understanding of the context within which these chips will actually be used. Impact statement The rapid pace of scientific innovation in the tissue chip (TC) field requires a cohesive partnership between innovators and end users. Near term uptake of these human-relevant platforms will fill gaps in current capabilities for assessing important properties of disposition, efficacy and safety liabilities. Similarly, these platforms could support mechanistic studies which aim to resolve challenges later in development (e.g. assessing the human relevance of a liability identified in animal studies). Building confidence that novel capabilities of TCs can address real world challenges while they themselves are being developed will accelerate their application in the discovery and development of innovative medicines. This article outlines a strategic roadmap to unite innovators and end users thus making implementation smooth and rapid. With the collective contributions from multiple international pharmaceutical companies and partners at National Institutes of Health, this article should serve as an invaluable resource to the multi-disciplinary field of TC development.

Periodontal ligament versus bone marrow mesenchymal stem cells in combination with Bio-Oss scaffolds for ectopic and in situ bone formation: A comparative study in the rat.

PubMed

Yu, Bo-Han; Zhou, Qian; Wang, Zuo-Lin

2014-08-01

The aim of this study was to compare the osteogenic effects of periodontal ligament stem cells (PDLSCs) versus bone marrow mesenchymal stem cells (BMMSCs) in combination with Bio-Oss scaffolds on subcutaneous and critical-size defects in the immunodeficient rat calvarium. PDLSCs and BMMSCs were obtained from the same canine donor. Twenty-four rats were randomly assigned to one of four experimental groups (n = 6 each): group A (no-graft negative control), group B (Bio-Oss positive control), group C (BMMSC/Bio-Oss test group), and group D (PDLSC/Bio-Oss test group). Eight weeks post-transplantation, ectopic and in situ bone regeneration was evaluated by micro-computed tomography (µ-CT), histology, histomorphometry, and immunohistochemistry. The stem cell/Bio-Oss constructs were significantly superior to the controls in terms of their ability to promote osteogenesis (p < 0.01), while the PDLSC/Bio-Oss construct tended to be superior to the BMMSC/Bio-Oss construct. Thus, engineered stem cell/Bio-Oss complexes can successfully reconstruct critical-size defects in rats, and PDLSCs and BMMSCs are both suitable as seed cells. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

7 CFR 52.3188 - Work sheet for dried prunes.

Code of Federal Regulations, 2011 CFR

2011-01-01

... defects, including off-color and poor texture 20 percent Poor texture, end cracks, skin or flesh damage, 3..., decay But no more than 6 percent But no more than 8 percent End cracks,2 skin or flesh damage, 3... (including all factors) 1 Percentages of defects are “by weight.” 2 Except that each 1 percent of end cracks...

Calpain-Mediated positional information directs cell wall orientation to sustain plant stem cell activity, growth and development

USDA-ARS?s Scientific Manuscript database

Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental f...

The study of develop optimization to control various resist defect in Photomask fabrication

NASA Astrophysics Data System (ADS)

Lim, JongHoon; Kim, ByungJu; Son, JaeSik; Park, EuiSang; Kim, SangPyo; Yim, DongGyu

2015-07-01

To reduce the pattern size in photomask is an inevitable trend because of the minimization of chip size. So it makes a big challenge to control defects in photomask industry. Defects below a certain size that had not been any problem in previous technology node are becoming an issue as the patterns are smaller. Therefore, the acceptable tolerance levels for current defect size and quantity are dramatically reduced. Because these defects on photomask can be the sources of the repeating defects on wafer, small size defects smaller than 200nm should not be ignored any more. Generally, almost defects are generated during develop process and etch process. Especially it is difficult to find the root cause of defects formed during the develop process because of their various types and very small size. In this paper, we studied how these small defects can be eliminated by analyzing the defects and tuning the develop process. There are 3 types of resist defects which are named as follows. The first type is `Popcorn' defect which is mainly occurred in negative resist and exists on the dark features. The second type is `Frog eggs' defect which is occurred in 2nd process of HTPSM and exists on the wide space area. The last type is `Spot' defect which also exists on the wide space area. These defects are generally appeared on the entire area of a plate and the number of these defects is about several hundred. It is thought that the original source is the surface's hydrophilic state before develop process or the incongruity between resist and developer. This study shows that the optimizing the develop process can be a good solution for some resist defects.

Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.

PubMed

Koga, Hideyuki; Shimaya, Masayuki; Muneta, Takeshi; Nimura, Akimoto; Morito, Toshiyuki; Hayashi, Masaya; Suzuki, Shiro; Ju, Young-Jin; Mochizuki, Tomoyuki; Sekiya, Ichiro

2008-01-01

Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect. For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined. Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment. Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.

Field-programmable lab-on-a-chip based on microelectrode dot array architecture.

PubMed

Wang, Gary; Teng, Daniel; Lai, Yi-Tse; Lu, Yi-Wen; Ho, Yingchieh; Lee, Chen-Yi

2014-09-01

The fundamentals of electrowetting-on-dielectric (EWOD) digital microfluidics are very strong: advantageous capability in the manipulation of fluids, small test volumes, precise dynamic control and detection, and microscale systems. These advantages are very important for future biochip developments, but the development of EWOD microfluidics has been hindered by the absence of: integrated detector technology, standard commercial components, on-chip sample preparation, standard manufacturing technology and end-to-end system integration. A field-programmable lab-on-a-chip (FPLOC) system based on microelectrode dot array (MEDA) architecture is presented in this research. The MEDA architecture proposes a standard EWOD microfluidic component called 'microelectrode cell', which can be dynamically configured into microfluidic components to perform microfluidic operations of the biochip. A proof-of-concept prototype FPLOC, containing a 30 × 30 MEDA, was developed by using generic integrated circuits computer aided design tools, and it was manufactured with standard low-voltage complementary metal-oxide-semiconductor technology, which allows smooth on-chip integration of microfluidics and microelectronics. By integrating 900 droplet detection circuits into microelectrode cells, the FPLOC has achieved large-scale integration of microfluidics and microelectronics. Compared to the full-custom and bottom-up design methods, the FPLOC provides hierarchical top-down design approach, field-programmability and dynamic manipulations of droplets for advanced microfluidic operations.

Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.

PubMed

Veronesi, Francesca; Maglio, Melania; Tschon, Matilde; Aldini, Nicolò Nicoli; Fini, Milena

2014-07-01

Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc.

Chondrogenic potential of injectable κ-carrageenan hydrogel with encapsulated adipose stem cells for cartilage tissue-engineering applications.

PubMed

Popa, Elena G; Caridade, Sofia G; Mano, João F; Reis, Rui L; Gomes, Manuela E

2015-05-01

Due to the limited self-repair capacity of cartilage, regenerative medicine therapies for the treatment of cartilage defects must use a significant amount of cells, preferably applied using a hydrogel system that can promise their delivery and functionality at the specific site. This paper discusses the potential use of κ-carrageenan hydrogels for the delivery of stem cells obtained from adipose tissue in the treatment of cartilage tissue defects. The developed hydrogels were produced by an ionotropic gelation method and human adipose stem cells (hASCs) were encapsulated in 1.5% w/v κ-carrageenan solution at a cell density of 5 × 10(6) cells/ml. The results from the analysis of the cell-encapsulating hydrogels, cultured for up to 21 days, indicated that κ-carrageenan hydrogels support the viability, proliferation and chondrogenic differentiation of hASCs. Additionally, the mechanical analysis demonstrated an increase in stiffness and viscoelastic properties of κ-carrageenan gels with their encapsulated cells with increasing time in culture with chondrogenic medium. These results allowed the conclusion that κ-carrageenan exhibits properties that enable the in vitro functionality of encapsulated hASCs and thus may provide the basis for new successful approaches for the treatment of cartilage defects. Copyright © 2013 John Wiley & Sons, Ltd.

Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET.

PubMed

Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; van Bokhoven, Hans; Wiman, Klas G; Zhou, Huiqing; Aberdam, Daniel; Petit, Isabelle

2013-02-05

Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18(+) cells but failed to further differentiate into K14(+) cells (epidermis/limbus) or K3/K12(+) cells (corneal epithelium). APR-246 (PRIMA-1(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves the way for future therapy of EEC.

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

PubMed

Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

2016-11-01

Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

PubMed

Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

2013-11-15

Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Electromechanical control of nitrogen-vacancy defect emission using graphene NEMS

PubMed Central

Reserbat-Plantey, Antoine; Schädler, Kevin G.; Gaudreau, Louis; Navickaite, Gabriele; Güttinger, Johannes; Chang, Darrick; Toninelli, Costanza; Bachtold, Adrian; Koppens, Frank H. L.

2016-01-01

Despite recent progress in nano-optomechanics, active control of optical fields at the nanoscale has not been achieved with an on-chip nano-electromechanical system (NEMS) thus far. Here we present a new type of hybrid system, consisting of an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. Electromechanical control of the photons emitted by the NVC is provided by electrostatic tuning of the graphene NEMS position, which is transduced to a modulation of NVC emission intensity. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field dipole–dipole interaction. This class of optomechanical coupling increases strongly for smaller distances, making it suitable for nanoscale devices. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, integrated optomechanical information processing and open new avenues towards quantum optomechanics. PMID:26742541

Bioengineered Systems and Designer Matrices That Recapitulate the Intestinal Stem Cell Niche.

PubMed

Wang, Yuli; Kim, Raehyun; Hinman, Samuel S; Zwarycz, Bailey; Magness, Scott T; Allbritton, Nancy L

2018-03-01

The relationship between intestinal stem cells (ISCs) and the surrounding niche environment is complex and dynamic. Key factors localized at the base of the crypt are necessary to promote ISC self-renewal and proliferation, to ultimately provide a constant stream of differentiated cells to maintain the epithelial barrier. These factors diminish as epithelial cells divide, migrate away from the crypt base, differentiate into the postmitotic lineages, and end their life span in approximately 7 days when they are sloughed into the intestinal lumen. To facilitate the rapid and complex physiology of ISC-driven epithelial renewal, in vivo gradients of growth factors, extracellular matrix, bacterial products, gases, and stiffness are formed along the crypt-villus axis. New bioengineered tools and platforms are available to recapitulate various gradients and support the stereotypical cellular responses associated with these gradients. Many of these technologies have been paired with primary small intestinal and colonic epithelial cells to re-create select aspects of normal physiology or disease states. These biomimetic platforms are becoming increasingly sophisticated with the rapid discovery of new niche factors and gradients. These advancements are contributing to the development of high-fidelity tissue constructs for basic science applications, drug screening, and personalized medicine applications. Here, we discuss the direct and indirect evidence for many of the important gradients found in vivo and their successful application to date in bioengineered in vitro models, including organ-on-chip and microfluidic culture devices.

Proximal Femoral Reconstructions with Bone Impaction Grafting and Metal Mesh

PubMed Central

Comba, Fernando; Piccaluga, Francisco

2009-01-01

Extensive circumferential proximal cortical bone loss is considered by some a contraindication for impaction bone grafting in the femur. We asked whether reconstruction with a circumferential metal mesh, impacted bone allografts, and a cemented stem would lead to acceptable survival in these patients. We retrospectively reviewed 14 patients (15 hips) with severe proximal femoral bone defects (average, 12 cm long; 14 type IV and one type IIIB using the classification of Della Valle and Paprosky) reconstructed with this method. The minimum followup was 20 months (average, 43.2 months; range, 20–72 months). Preoperative Merle D’Aubigné and Postel score averaged 4.8 points. With revision of the stem as the end point, the survivorship of the implant was 100% at one year and 86.6% at 72 months. The mean functional score at last followup was 14.4 points. We observed two fractures of the metal mesh at 31 and 48 months in cases reconstructed with a stem that did not bypass the mesh. Dislocation (3 cases) and acute deep infection (3 cases) were the most frequent complications. Patients with complete absence of the proximal femur may be candidates for biological proximal femoral reconstructions using this salvage procedure. Bone impaction grafting must be a routine technique if this method is selected. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:19294476

Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

PubMed

Zhang, S; Chu, W C; Lai, R C; Lim, S K; Hui, J H P; Toh, W S

2016-12-01

Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 μg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Magnetic resonance imaging tractography as a diagnostic tool in patients with spinal cord injury treated with human embryonic stem cells.

PubMed

Shroff, Geeta

2017-02-01

Introduction Spinal cord injury is a cause of severe disability and mortality. The pharmacological and non-pharmacological methods used, are unable to improve the quality of life in spinal cord injury. Spinal disorders have been treated with human embryonic stem cells. Magnetic resonance imaging and tractography were used as imaging modality to document the changes in the damaged cord, but the magnetic resonance imaging tractography was seen to be more sensitive in detecting the changes in the spinal cord. The present study was conducted to evaluate the diagnostic modality of magnetic resonance imaging tractography to determine the efficacy of human embryonic stem cells in chronic spinal cord injury. Materials and methods The study included the patients with spinal cord injury for whom magnetic resonance imaging tractography was performed before and after the therapy. Omniscan (gadodiamide) magnetic resonance imaging tractography was analyzed to assess the spinal defects and the improvement by human embryonic stem cell treatment. The patients were also scored by American Spinal Injury Association scale. Results Overall, 15 patients aged 15-44 years with clinical manifestations of spinal cord injury had magnetic resonance imaging tractography performed. The average treatment period was nine months. The majority of subjects ( n = 13) had American Spinal Injury Association score A, and two patients were at score C at the beginning of therapy. At the end of therapy, 10 patients were at score A, two patients were at score B and three patients were at score C. Improvements in patients were clearly understood through magnetic resonance imaging tractography as well as in clinical signs and symptoms. Conclusion Magnetic resonance imaging tractography can be a crucial diagnostic modality to assess the improvement in spinal cord injury patients.

Visual and x-ray inspection characteristics of eutectic and lead free assemblies

NASA Technical Reports Server (NTRS)

Ghaffarian, R.

2003-01-01

For high reliability applications, visual inspection has been the key technique for most conventional electronic package assemblies. Now, the use of x-ray technique has become an additional inspection requirement for quality control and detection of unique defects due to manufacturing of advanced electronic array packages such as ball grid array (BGAs) and chip scale packages (CSPs).

Electrochemical Detection of Human Mesenchymal Stem Cell Differentiation on Fabricated Gold Nano-Dot Cell Chips.

PubMed

An, Jeung Hee; Kim, Seung U; Park, Mi-Kyung; Choi, Jeong Woo

2015-10-01

Human mesenchymal stem cells (MSCs) have the capacity for self-renewal and maintain pluripotency, which is defined by their ability to differentiate into cells such as osteoblasts, neurons, and glial cells. In this study, we report a method for defining the status of human MSCs based on electrochemical detection systems. Gold nano-dot structures were fabricated using a nanoporous alumina mask, and the structural formations were confirmed by scanning electron microscopy (SEM). Human MSCs were allowed to attach to RGD (Arg-Gly-Asp) peptide nanopatterned surfaces, and electrochemical tools were applied to the MSCs attached on the chip surface. The cultured MSCs were shown to differentiate into neural cell types, as indicated by immunocytochemical staining for tyrosine hydroxylase and beta tubulin III. Following treatment with basic fibroblast growth factor (bFGF) for 14 days, most of the B10 cells exhibited bipolar or multipolar morphology with branched processes, and the proportion of B10 cells expressing neuronal cell markers considerably increased. Electrophysiological recordings from MSCs treated with bFGF for 5-14 days were examined with cyclic voltammetry, and the electrochemical signals were shown to increase during differentiation from MSCs to neuronal cells. This human MSC cell line is a useful tool for studying organogenesis, specifically neurogenesis, and in addition, the cell line provides a valuable source of cells for cell therapy. The electrochemical measurement system proposed here could be utilized in electrical cell chips for numerous applications, including cell differentiation, disease diagnosis, drug detection, and on-site monitoring.

[Fatigue damage analysis of porcelain in all-ceramic crowns].

PubMed

Liu, Yi-hong; Feng, Hai-lan; Liu, Guang-hua; Shen, Zhi-jian

2010-02-18

To investigate the fatigue damage mechanism of porcelain, and its relation with the microscopic defects in clinically failed all-ceramic crowns. Collecting the bilayered all-ceramic crowns failed in vivo. The fractured surfaces and occlusial surfaces of failed crowns were examined by an optical microscope followed by detailed fractography investigations using a field emission scanning electron microscope. When chemical impurities were of concern, energy-dispersive X-ray spectroscopy analysis was performed to examine chemical composition. A standard practice for fractography failure analysis of advanced ceramics is applied to disclose the fracture mode, and damage character. Three types of fracture features are defined as breakdown of the entire crown, and porcelain chipping-off/delamination. Alumina crowns were usually characterized by breakdown of the entire crown, while zirconia crowns by porcelain chipping-off and delamination. The fatigue damage of porcelain was classified into surface wear, cone crack, and porcelain delamination. The observed microscopic defects in this study included air bubbles and impurity particles. The multi-point occlusial contacts were recommended in all-ceramic restorations clinically. The thickness of porcelain is important for the anti-fatigue ability of porcelain. Cautions have to be taken to avoid contaminations during the veneering processes.

First-principles engineering of charged defects for two-dimensional quantum technologies

NASA Astrophysics Data System (ADS)

Wu, Feng; Galatas, Andrew; Sundararaman, Ravishankar; Rocca, Dario; Ping, Yuan

2017-12-01

Charged defects in two-dimensional (2D) materials have emerging applications in quantum technologies such as quantum emitters and quantum computation. The advancement of these technologies requires a rational design of ideal defect centers, demanding reliable computation methods for the quantitatively accurate prediction of defect properties. We present an accurate, parameter-free, and efficient procedure to evaluate the quasiparticle defect states and thermodynamic charge transition levels of defects in 2D materials. Importantly, we solve critical issues that stem from the strongly anisotropic screening in 2D materials, that have so far precluded the accurate prediction of charge transition levels in these materials. Using this procedure, we investigate various defects in monolayer hexagonal boron nitride (h -BN ) for their charge transition levels, stable spin states, and optical excitations. We identify CBVN (nitrogen vacancy adjacent to carbon substitution of boron) to be the most promising defect candidate for scalable quantum bit and emitter applications.

Accelerated defect visualization of microelectronic systems using binary search with fixed pitch-catch distance laser ultrasonic scanning

NASA Astrophysics Data System (ADS)

Park, Byeongjin; Sohn, Hoon

2018-04-01

The practicality of laser ultrasonic scanning is limited because scanning at a high spatial resolution demands a prohibitively long scanning time. Inspired by binary search, an accelerated defect visualization technique is developed to visualize defect with a reduced scanning time. The pitch-catch distance between the excitation point and the sensing point is also fixed during scanning to maintain a high signal-to-noise ratio of measured ultrasonic responses. The approximate defect boundary is identified by examining the interactions between ultrasonic waves and defect observed at the scanning points that are sparsely selected by a binary search algorithm. Here, a time-domain laser ultrasonic response is transformed into a spatial ultrasonic domain response using a basis pursuit approach so that the interactions between ultrasonic waves and defect can be better identified in the spatial ultrasonic domain. Then, the area inside the identified defect boundary is visualized as defect. The performance of the proposed defect visualization technique is validated through an experiment on a semiconductor chip. The proposed defect visualization technique accelerates the defect visualization process in three aspects: (1) The number of measurements that is necessary for defect visualization is dramatically reduced by a binary search algorithm; (2) The number of averaging that is necessary to achieve a high signal-to-noise ratio is reduced by maintaining the wave propagation distance short; and (3) With the proposed technique, defect can be identified with a lower spatial resolution than the spatial resolution required by full-field wave propagation imaging.

Silvicultural tools applicable in forests burned by a mixed severity fire regime

Treesearch

Russell T. Graham; Theresa B. Jain

2005-01-01

The silvicultural tools applicable for use in forests burned by mixed severity fire regimes are as highly variable as the structures and compositions the fires have historically created. Singly or in combination chunking, chipping, slashing, and piling can alter the character of surface fuels (e.g., small trees, shrubs, branches, and stems). These treatments can be...

Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

PubMed

Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

2018-05-04

Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

Demineralized Bone Matrix Scaffolds Modified by CBD-SDF-1α Promote Bone Regeneration via Recruiting Endogenous Stem Cells.

PubMed

Shi, Jiajia; Sun, Jie; Zhang, Wen; Liang, Hui; Shi, Qin; Li, Xiaoran; Chen, Yanyan; Zhuang, Yan; Dai, Jianwu

2016-10-07

The reconstruction of bone usually depends on substitute transplantation, which has drawbacks including the limited bone substitutes available, comorbidity, immune rejection, and limited endogenous bone regeneration. Here, we constructed a functionalized bone substitute by combining application of the demineralized bone matrix (DBM) and collagen-binding stromal-cell-derived factor-1α (CBD-SDF-1α). DBM was a poriferous and biodegradable bone substitute, derived from bovine bone and consisting mainly of collagen. CBD-SDF-1α could bind to collagen and be controllably released from the DBM to mobilize stem cells. In a rat femur defect model, CBD-SDF-1α-modified DBM scaffolds could efficiently mobilize CD34 + and c-kit + endogenous stem cells homing to the injured site at 3 days after implantation. According to the data from micro-CT, CBD-SDF-1α-modified DBM scaffolds could help the bone defects rejoin with mineralization accumulated and bone volume expanded. Interestingly, osteoprotegerin (OPG) and osteopontin (OPN) were highly expressed in CBD-SDF-1α group at an early time after implantation, while osteocalcin (OCN) was more expanded. H&E and Masson's trichrome staining showed that the CBD-SDF-1α-modified DBM scaffold group had more osteoblasts and that the bone defect rejoined earlier. The ultimate strength of the regenerated bone was investigated by three-point bending, showing that the CBD-SDF-1α group had superior strength. In conclusion, CBD-SDF-1α-modified DBM scaffolds could promote bone regeneration by recruiting endogenous stem cells.

In situ electrochemical detection of embryonic stem cell differentiation.

PubMed

Yea, Cheol-Heon; An, Jeung Hee; Kim, Jungho; Choi, Jeong-Woo

2013-06-20

Stem cell sensors have emerged as a promising technique to electrochemically monitor the functional status and viability of stem cells. However, efficient electrochemical analysis techniques are required for the development of effective electrochemical stem cell sensors. In the current study, we report a newly developed electrochemical cyclic voltammetry (CV) system to determine the status of mouse embryonic stem (ES) cells. 1-Naphthly phosphate (1-NP), which was dephosphorylated by alkaline phosphatase into a 1-naphthol on an undifferentiated mouse ES cell, was used as a substrate to electrochemically monitor the differentiation status of mouse ES cells. The peak current in the cyclic voltammetry of 1-NP increased linearly with the concentration of pure 1-NP (R(2)=0.9623). On the other hand, the peak current in the electrochemical responses of 1-NP decreased as the number of undifferentiated ES cells increased. The increased dephosphorylation of 1-NP to 1-naphthol made a decreased electrochemical signal. Non-toxicity of 1-NP was confirmed. In conclusion, the proposed electrochemical analysis system can be applied to an electrical stem cell chip for diagnosis, drug detection and on-site monitoring. Copyright © 2013 Elsevier B.V. All rights reserved.

Mutations That Affect the Efficiency of Translation of mRNA for the cII Gene of Coliphage Lambda

PubMed Central

Dul, Ed; Mahoney, Michael E.; Wulff, Daniel L.

1987-01-01

Starting with the λ pRE- strain λctr1 cy3008, which forms clear plaques, we have isolated two mutant strains, λdya2 ctr1 cy3008 and λ dya3 ctr1 cy3008, that form plaques with very slightly turbid centers. The dya2 and dya3 mutations lie in the region of overlap between the PRE promoter and the ribosome recognition region of the cII gene, and have nucleotide alterations at positions -1 and +5 of pRE, and alterations of cII mRNA at -16 and -21 nucleotides before the initial AUG codon of the gene. Both mutations destabilize a stem structure that may be formed by cII mRNA, and dya2 also changes the sequence on cII mRNA that is complementary to the 3'-end of 16 S rRNA from 5'-UAAGGA-3' to 5'-UGAGGA-3'.—The dya2 and dya3 mutations, along with the ctr1 mutation, which destabilizes either of two alternate stem structures which may be formed by cII mRNA (these being more stable stem structures than the one affected by dya2 and dya3), were tested for their ability to reverse two cII- mutations that are characterized by inefficient translation of cII mRNA. These are cII3088, an A → G mutation four bases before the initial AUG codon, and cII3059 , a GUU → GAU (Val2 → Asp) second codon mutation. It was found that ctr1 completely reverses the translation defects of these two mutations, while dya2 partially reverses these translation defects. The dya3 mutation has no effect on translation efficiency under any condition tested. However neither the ctr1 mutation nor the dya2 mutation has much effect on translation efficiency in an otherwise cII+ background, indicating that other factors must limit the rate of translation of cII mRNA under these conditions. PMID:2953647

Fiber optic to integrated optical chip coupler

NASA Technical Reports Server (NTRS)

Pikulski, Joseph I. (Inventor); Ramer, O. Glenn (Inventor)

1987-01-01

Optical fibers are clamped by a block onto a substrate. Thereupon, metal is plated over the fibers to hold them in place upon the substrate. The clamp block is removed and the opening, resulting from the clamp block's presence, is then plated in. The built-up metallic body is a coupling which holds the fibers in position so that the ends can be polished for coupling to an integrated optical chip upon a coupling fixture.

Changes in stem quality of young thinned hardwoods

Treesearch

David L. Sonderman; David L. Sonderman

1986-01-01

Describes changes in limb-related defects on 18-year-old, even-aged hardwoods 6 years after thinning. Stocking levels of 30, 45, and 60 percent were studied. There were fewer defects per square foot of surface area in the higher stocking plots than in the lower stocking plots. The average number of live limbs decreased 83 percent in the unthinned plots and increased...

Predicting internal yellow-poplar log defect features using surface indicators

Treesearch

R. Edward Thomas

2008-01-01

Determining the defects that are located within the log is crucial to understanding the tree/log resource for efficient processing. However, existing means of doing this non-destructively requires the use of expensive X-ray/CT, MRI, or microwave technology. These methods do not lend themselves to fast, efficient, and cost-effective analysis of logs and tree stems in...

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

Atherosclerosis and clonal hematopoyesis: A new risk factor.

PubMed

Páramo Fernández, José A

Recent research has revealed that clonal hematopoyesis of indeterminate potential (CHIP) characterized by the acquisition of somatic mutations in hematopoietic stem cells, is not only a common age-related disorder and a premalignant condition, but it is also associated with the development of atherosclerotic vascular diseases. Mutations in DNMT3A, TET2 and ASXL1 were each individually associated with coronary heart disease, stroke and coronary calcification. Therefore, CHIP emerges as a new risk factor for atherosclerotic vascular pathologies and its detection may be relevant as a new therapeutic target in order to modify the natural course of the disease. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Potential roughness near lithographically fabricated atom chips

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krueger, P.; Laboratoire Kastler Brossel, Ecole Normale Superieure, 24 Rue Lhomond, F-75005 Paris; Andersson, L. M.

2007-12-15

Potential roughness has been reported to severely impair experiments in magnetic microtraps. We show that these obstacles can be overcome as we measure disorder potentials that are reduced by two orders of magnitude near lithographically patterned high-quality gold layers on semiconductor atom chip substrates. The spectrum of the remaining field variations exhibits a favorable scaling. A detailed analysis of the magnetic field roughness of a 100-{mu}m-wide wire shows that these potentials stem from minute variations of the current flow caused by local properties of the wire rather than merely from rough edges. A technique for further reduction of potential roughnessmore » by several orders of magnitude based on time-orbiting magnetic fields is outlined.« less

Allogeneic adipose-derived stem cells regenerate bone in a critical-sized ulna segmental defect

PubMed Central

Wen, Congji; Yan, Hai; Fu, Shibo; Qian, Yunliang

2016-01-01

Adipose-derived stem cells (ASCs) with multilineage potential can be induced into osteoblasts, adipocytes and chondrocytes. ASCs as seed cell are widely used in the field of tissue engineering, but most studies either use autologous cells as the source or an immunodeficient animal as the host. In our present study, we explored the feasibility of applying allogeneic ASCs and demineralized bone matrix (DBM) scaffolds for repairing tubular bone defects without using immunosuppressive therapy. Allogeneic ASCs were expanded and seeded on DBM scaffolds and induced to differentiate along the osteogenic lineage. Eight Sprague–Dawley (SD) rats were used in this study and bilateral critical-sized defects (8 mm) of the ulna were created and divided into two groups: with ASC-DBM constructs or DBM alone. The systemic immune response and the extent of bone healing were evaluated post-operatively. Twenty-four weeks after implantation, digital radiography (DR) testing showed that new bones had formed in the experimental group. By contrast, no bone tissue formation was observed in the control group. This study demonstrated that allogeneic ASCs could promote bone regeneration and repair tubular bone defects combined with DBM by histologically typical bone without systemic immune response PMID:25819682

The Drosophila nuclear lamina protein otefin is required for germline stem cell survival.

PubMed

Barton, Lacy J; Pinto, Belinda S; Wallrath, Lori L; Geyer, Pamela K

2013-06-24

LEM domain (LEM-D) proteins are components of an extensive protein network that assembles beneath the inner nuclear envelope. Defects in LEM-D proteins cause tissue-restricted human diseases associated with altered stem cell homeostasis. Otefin (Ote) is a Drosophila LEM-D protein that is intrinsically required for female germline stem cell (GSC) maintenance. Previous studies linked Ote loss with transcriptional activation of the key differentiation gene bag-of-marbles (bam), leading to the model in which Ote tethers the bam gene to the nuclear periphery for gene silencing. Using genetic and phenotypic analyses of multiple ote(-/-) backgrounds, we obtained evidence that is inconsistent with this model. We show that bam repression is maintained in ote(-/-) GSCs and that germ cell loss persists in ote(-/-), bam(-/-) mutants, together demonstrating that GSC loss is independent of bam transcription. We show that the primary defect in ote(-/-) GSCs is a block of differentiation, which ultimately leads to germ cell death. Copyright © 2013 Elsevier Inc. All rights reserved.

Periodontal Ligament Stem Cell-Mediated Treatment for Periodontitis in Miniature Swine

PubMed Central

Liu, Yi; Zheng, Ying; Ding, Gang; Fang, Dianji; Zhang, Chunmei; Bartold, Peter Mark; Gronthos, Stan; Shi, Songtao; Wang, Songlin

2009-01-01

Periodontitis is a periodontal tissue infectious disease and the most common cause for tooth loss in adults. It has been linked to many systemic disorders, such as coronary artery disease, stroke, and diabetes. At present, there is no ideal therapeutic approach to cure periodontitis and achieve optimal periodontal tissue regeneration. In this study, we explored the potential of using autologous periodontal ligament stem cells (PDLSCs) to treat periodontal defects in a porcine model of periodontitis. The periodontal lesion was generated in the first molars area of miniature pigs by the surgical removal of bone and subsequent silk ligament suture around the cervical portion of the tooth. Autologous PDLSCs were obtained from extracted teeth of the miniature pigs and then expanded ex vivo to enrich PDLSC numbers. When transplanted into the surgically created periodontal defect areas, PDLSCs were capable of regenerating periodontal tissues, leading to a favorable treatment for periodontitis. This study demonstrates the feasibility of using stem cell-mediated tissue engineering to treat periodontal diseases. PMID:18238856

A three-dimensional bucking system for optimal bucking of Central Appalachian hardwoods

Treesearch

Jingxin Wang; Jingang Liu; Chris B. LeDoux

2009-01-01

An optimal tree stembucking systemwas developed for central Appalachian hardwood species using three-dimensional (3D) modeling techniques. ActiveX Data Objects were implemented via MS Visual C++/OpenGL to manipulate tree data which were supported by a backend relational data model with five data entity types for stems, grades and prices, logs, defects, and stem shapes...

Effect of thinning on mixed-oak stem quality

Treesearch

David L. Sonderman; Everette D. Rast; Everette D. Rast

1988-01-01

Changes in limb-;elated stem defect were studied from 1977 to 1982 on 595 mixed-oak trees fbllowing a schedule of thinnings dating back to 1962. All of the thinnings were controlled by stocking goals rather than predetermined time intervals. Results show that heavy and moderate thinnings, as opposed to light thinnings,lhad an adverse effect on the number and size of...

Stem cell research: applicability in dentistry.

PubMed

Mathur, Shivani; Chopra, Rahul; Pandit, I K; Srivastava, Nikhil; Gugnani, Neeraj

2014-01-01

In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, the inability of most tissues and organs to repair and regenerate after damage is a problem that needs to be solved. Stem cell research is being pursued in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells that will offer hope to people suffering from various ailments. Regeneration of damaged periodontal tissue, bone, pulp, and dentin is a problem that dentists face today. Stem cells present in dental pulp, periodontal ligament, and alveolar bone marrow have the potential to repair and regenerate teeth and periodontal structures. These stem cells can be harvested from dental pulp, periodontal ligament, and/or alveolar bone marrow; expanded; embedded in an appropriate scaffold; and transplanted back into a defect to regenerate bone and tooth structures. These cells have the potential to regenerate dentin, periodontal ligament, and cementum and can also be used to restore bone defects. The kind of scaffold, the source of cells, the type of in vitro culturing, and the type of surgical procedure to be used all require careful consideration. The endeavor is clearly multidisciplinary in nature, and the practicing dental surgeon has a critical role in it. Playing this role in the most effective way requires awareness of the huge potential associated with the use of stem cells in a clinical setting, as well as a proper understanding of the related problems.

Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

PubMed

Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2004-01-01

The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

2016-01-01

Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

FANCL ubiquitinates β-catenin and enhances its nuclear function.

PubMed

Dao, Kim-Hien T; Rotelli, Michael D; Petersen, Curtis L; Kaech, Stefanie; Nelson, Whitney D; Yates, Jane E; Hanlon Newell, Amy E; Olson, Susan B; Druker, Brian J; Bagby, Grover C

2012-07-12

Bone marrow failure is a nearly universal complication of Fanconi anemia. The proteins encoded by FANC genes are involved in DNA damage responses through the formation of a multisubunit nuclear complex that facilitates the E3 ubiquitin ligase activity of FANCL. However, it is not known whether loss of E3 ubiquitin ligase activity accounts for the hematopoietic stem cell defects characteristic of Fanconi anemia. Here we provide evidence that FANCL increases the activity and expression of β-catenin, a key pluripotency factor in hematopoietic stem cells. We show that FANCL ubiquitinates β-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions. Specifically, β-catenin modified with lysine-11 ubiquitin chain extension efficiently activates a lymphocyte enhancer-binding factor-T cell factor reporter. We also show that FANCL-deficient cells display diminished capacity to activate β-catenin leading to reduced transcription of Wnt-responsive targets c-Myc and Cyclin D1. Suppression of FANCL expression in normal human CD34(+) stem and progenitor cells results in fewer β-catenin active cells and inhibits expansion of multilineage progenitors. Together, these results suggest that diminished Wnt/β-catenin signaling may be an underlying molecular defect in FANCL-deficient hematopoietic stem cells leading to their accelerated loss.

Effect of aging on stem cells

PubMed Central

Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

2017-01-01

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects. PMID:28261550

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

PubMed

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-09-04

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer

PubMed Central

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R k; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-01-01

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors. PMID:28869585

Advanced in-production hotspot prediction and monitoring with micro-topography

NASA Astrophysics Data System (ADS)

Fanton, P.; Hasan, T.; Lakcher, A.; Le-Gratiet, B.; Prentice, C.; Simiz, J.-G.; La Greca, R.; Depre, L.; Hunsche, S.

2017-03-01

At 28nm technology node and below, hot spot prediction and process window control across production wafers have become increasingly critical to prevent hotspots from becoming yield-limiting defects. We previously established proof of concept for a systematic approach to identify the most critical pattern locations, i.e. hotspots, in a reticle layout by computational lithography and combining process window characteristics of these patterns with across-wafer process variation data to predict where hotspots may become yield impacting defects [1,2]. The current paper establishes the impact of micro-topography on a 28nm metal layer, and its correlation with hotspot best focus variations across a production chip layout. Detailed topography measurements are obtained from an offline tool, and pattern-dependent best focus (BF) shifts are determined from litho simulations that include mask-3D effects. We also establish hotspot metrology and defect verification by SEM image contour extraction and contour analysis. This enables detection of catastrophic defects as well as quantitative characterization of pattern variability, i.e. local and global CD uniformity, across a wafer to establish hotspot defect and variability maps. Finally, we combine defect prediction and verification capabilities for process monitoring by on-product, guided hotspot metrology, i.e. with sampling locations being determined from the defect prediction model and achieved prediction accuracy (capture rate) around 75%

Trehalose Improves Human Fibroblast Deficits in a New CHIP-Mutation Related Ataxia

PubMed Central

Casarejos, Maria Jose; Perucho, Juan; López-Sendón, Jose Luis; García de Yébenes, Justo; Bettencourt, Conceição; Gómez, Ana; Ruiz, Carolina; Heutink, Peter; Rizzu, Patrizia; Mena, Maria Angeles

2014-01-01

In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein misfolding and proteostasis were evaluated. Recent studies have revealed that mutations in STUB-1 gene lead to a growing list of molecular defects as deregulation of protein quality, inhibition of proteasome, cell death, decreased autophagy and alteration in CHIP and HSP70 levels. In this CHIP-mutant patient fibroblasts the inhibition of proteasome with epoxomicin induced severe pathophysiological age-associated changes, cell death and protein ubiquitination. Additionally, treatment with epoxomicin produced a dose-dependent increase in the number of cleaved caspase-3 positive cells. However, co-treatment with trehalose, a disaccharide of glucose present in a wide variety of organisms and known as a autophagy enhancer, reduced these pathological events. Trehalose application also increased CHIP and HSP70 expression and GSH free radical levels. Furthermore, trehalose augmented macro and chaperone mediated autophagy (CMA), rising the levels of LC3, LAMP2, CD63 and increasing the expression of Beclin-1 and Atg5-Atg12. Trehalose treatment in addition increased the percentage of immunoreactive cells to HSC70 and LAMP2 and reduced the autophagic substrate, p62. Although this is an individual case based on only one patient and the statistical comparisons are not valid between controls and patient, the low variability among controls and the obvious differences with this patient allow us to conclude that trehalose, through its autophagy activation capacity, anti-aggregation properties, anti-oxidative effects and lack of toxicity, could be very promising for the treatment of CHIP-mutation related ataxia, and possibly a wide spectrum of neurodegenerative disorders related to protein disconformation. PMID:25259530

Wideband Fully-Programmable Dual-Mode CMOS Analogue Front-End for Electrical Impedance Spectroscopy

PubMed Central

Valente, Virgilio; Demosthenous, Andreas

2016-01-01

This paper presents a multi-channel dual-mode CMOS analogue front-end (AFE) for electrochemical and bioimpedance analysis. Current-mode and voltage-mode readouts, integrated on the same chip, can provide an adaptable platform to correlate single-cell biosensor studies with large-scale tissue or organ analysis for real-time cancer detection, imaging and characterization. The chip, implemented in a 180-nm CMOS technology, combines two current-readout (CR) channels and four voltage-readout (VR) channels suitable for both bipolar and tetrapolar electrical impedance spectroscopy (EIS) analysis. Each VR channel occupies an area of 0.48 mm2, is capable of an operational bandwidth of 8 MHz and a linear gain in the range between −6 dB and 42 dB. The gain of the CR channel can be set to 10 kΩ, 50 kΩ or 100 kΩ and is capable of 80-dB dynamic range, with a very linear response for input currents between 10 nA and 100 μA. Each CR channel occupies an area of 0.21 mm2. The chip consumes between 530 μA and 690 μA per channel and operates from a 1.8-V supply. The chip was used to measure the impedance of capacitive interdigitated electrodes in saline solution. Measurements show close matching with results obtained using a commercial impedance analyser. The chip will be part of a fully flexible and configurable fully-integrated dual-mode EIS system for impedance sensors and bioimpedance analysis. PMID:27463721

Self-priming compartmentalization digital LAMP for point-of-care.

PubMed

Zhu, Qiangyuan; Gao, Yibo; Yu, Bingwen; Ren, Hao; Qiu, Lin; Han, Sihai; Jin, Wei; Jin, Qinhan; Mu, Ying

2012-11-21

Digital nucleic acid amplification provides unprecedented opportunities for absolute nucleic acid quantification by counting of single molecules. This technique is useful for molecular genetic analysis in cancer, stem cell, bacterial, non-invasive prenatal diagnosis in which many biologists are interested. This paper describes a self-priming compartmentalization (SPC) microfluidic chip platform for performing digital loop-mediated amplification (LAMP). The energy for the pumping is pre-stored in the degassed bulk PDMS by exploiting the high gas solubility of PDMS; therefore, no additional structures other than channels and reservoirs are required. The sample and oil are sequentially sucked into the channels, and the pressure difference of gas dissolved in PDMS allows sample self-compartmentalization without the need for further chip manipulation such as with pneumatic microvalves and control systems, and so on. The SPC digital LAMP chip can be used like a 384-well plate, so, the world-to-chip fluidic interconnections are avoided. The microfluidic chip contains 4 separate panels, each panel contains 1200 independent 6 nL chambers and can be used to detect 4 samples simultaneously. Digital LAMP on the microfluidic chip was tested quantitatively by using β-actin DNA from humans. The self-priming compartmentalization behavior is roughly predictable using a two-dimensional model. The uniformity of compartmentalization was analyzed by fluorescent intensity and fraction of volume. The results showed that the feasibility and flexibility of the microfluidic chip platform for amplifying single nucleic acid molecules in different chambers made by diluting and distributing sample solutions. The SPC chip has the potential to meet the requirements of a general laboratory: power-free, valve-free, operating at isothermal temperature, inexpensive, sensitive, economizing labour time and reagents. The disposable analytical devices with appropriate air-tight packaging should be useful for point-of-care, and enabling it to become one of the common tools for biology research, especially, in point-of-care testing.

Stability and Antioxidant Activity of Annatto (Bixa orellana L.) Tocotrienols During Frying and in Fried Tortilla Chips.

PubMed

Winkler-Moser, Jill K; Bakota, Erica L; Hwang, Hong-Sik

2018-02-01

Annatto tocotrienols (AnT3), which contain approximately 90% δ-tocotrienol (δ-T3), were added to mid-oleic sunflower oil used for frying tortilla chips over 3 d. The objectives were to evaluate their stability during frying, absorption by the fried food, and activity as antioxidants in frying oil and in tortilla chips during storage. AnT3 did not significantly affect the stability of the oil during frying or the sensory profiles of freshly fried chips. The naturally present α-tocopherol (α-T) in the oil degraded at a lower rate in the presence of AnT3, resulting in significantly higher α-T by the end of the frying study. Levels of tocopherols and tocotrienols in the chips mirrored oil levels. AnT3 did not affect the sensory profile of the chips after 1 wk of storage at 50 °C, but after 3 wk of storage, the control chips had higher levels of painty and rancid flavors compared to chips with AnT3. Headspace hexanal was also significantly higher in the control chips compared to the chips with AnT3 after 3 wk of storage. Annatto tocotrienols, containing primarily delta- and gamma-tocotrienols, were added to mid-oleic sunflower oil used for frying tortilla chips. The tocotrienols were absorbed by the chips along with the oil. They slowed the degradation of α tocopherol during frying, and reduced levels of painty and rancid flavor scores as well as headspace hexanal in chips that were stored for 3 wk at elevated temperatures. The results indicated that fried snack foods such as tortilla chips may be a suitable and convenient vehicle for enriching tocotrienols in the diet, and that tocotrienols may also enhance the shelf-life of fried foods. © 2018 Institute of Food Technologists®.

High-temperature, high-pressure optical cell

NASA Technical Reports Server (NTRS)

Harris, R. P. (Inventor); Holland, L. R. (Inventor); Smith, R. E. (Inventor)

1986-01-01

The invention is an optical cell for containment of chemicals under conditions of high temperature and high pressure. The cell is formed of a vitreous silica tube, two optical windows comprising a vitreous silica rod inserted into the ends of a tube, and fused into position in the tube ends. Windows are spaced apart to form a cavity enclosed by the tube and the windows. A hole is drilled radially through the tube and into the cavity. Another vitreous silica tube is fused to the silica tube around the hole to form the stem, which is perpendicular to the long axis of the tube. The open end of the stem is used to load chemicals into the cavity. Then the stem may be sealed, and if desired, it may be shortened in order to reduce the volume of the cavity, which extends into the stem.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice.

PubMed

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-04-23

Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective.

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

THE MELTING MECHANISM OF DNA TETHERED TO A SURFACE

PubMed Central

QAMHIEH, KHAWLA; WONG, KA-YIU; LYNCH, GILLIAN C.; PETTITT, B. MONTGOMERY

2009-01-01

The details of melting of DNA immobilized on a chip or nanoparticle determines the sensitivity and operating characteristics of many analytical and synthetic biotechnological devices. Yet, little is known about the differences in how the DNA melting occurs between a homogeneous solution and that on a chip. We used molecular dynamics simulations to explore possible pathways for DNA melting on a chip. Simulation conditions were chosen to ensure that melting occurred in a submicrosecond timescale. The temperature was set to 400 K and the NaCl concentration was set to 0.1 M. We found less symmetry than in the solution case where for oligomeric double-stranded nucleic acids both ends melted with roughly equal probability. On a prepared silica surface we found melting is dominated by fraying from the end away from the surface. Strand separation was hindered by nonspecific surface adsorption at this temperature. At elevated temperatures the melted DNA was attracted to even uncharged organically coated surfaces demonstrating surface fouling. While hybridization is not the simple reverse of melting, this simulation has implications for the kinetics of hybridization. PMID:19802357

78 FR 23472 - Amendments to Existing Validated End-User Authorizations: CSMC Technologies Corporation in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... of Wuxi CR Semiconductor Wafers & Chips Co., Ltd. and CSMC Technologies Fab 1 Co., Ltd., which is... Validated End-User: CSMC Technologies Corporation. Eligible Destinations: CSMC Technologies Fab 1 Co., Ltd., 14 Liangxi Road, Wuxi, Jiangsu 214061, China. CSMC Technologies Fab 2 Co., Ltd., 8 Xinzhou Rd., Wuxi...

A MEMS-based, wireless, biometric-like security system

NASA Astrophysics Data System (ADS)

Cross, Joshua D.; Schneiter, John L.; Leiby, Grant A.; McCarter, Steven; Smith, Jeremiah; Budka, Thomas P.

2010-04-01

We present a system for secure identification applications that is based upon biometric-like MEMS chips. The MEMS chips have unique frequency signatures resulting from fabrication process variations. The MEMS chips possess something analogous to a "voiceprint". The chips are vacuum encapsulated, rugged, and suitable for low-cost, highvolume mass production. Furthermore, the fabrication process is fully integrated with standard CMOS fabrication methods. One is able to operate the MEMS-based identification system similarly to a conventional RFID system: the reader (essentially a custom network analyzer) detects the power reflected across a frequency spectrum from a MEMS chip in its vicinity. We demonstrate prototype "tags" - MEMS chips placed on a credit card-like substrate - to show how the system could be used in standard identification or authentication applications. We have integrated power scavenging to provide DC bias for the MEMS chips through the use of a 915 MHz source in the reader and a RF-DC conversion circuit on the tag. The system enables a high level of protection against typical RFID hacking attacks. There is no need for signal encryption, so back-end infrastructure is minimal. We believe this system would make a viable low-cost, high-security system for a variety of identification and authentication applications.

Silicon sample holder for molecular beam epitaxy on pre-fabricated integrated circuits

NASA Technical Reports Server (NTRS)

Hoenk, Michael E. (Inventor); Grunthaner, Paula J. (Inventor); Grunthaner, Frank J. (Inventor)

1994-01-01

The sample holder of the invention is formed of the same semiconductor crystal as the integrated circuit on which the molecular beam expitaxial process is to be performed. In the preferred embodiment, the sample holder comprises three stacked micro-machined silicon wafers: a silicon base wafer having a square micro-machined center opening corresponding in size and shape to the active area of a CCD imager chip, a silicon center wafer micro-machined as an annulus having radially inwardly pointing fingers whose ends abut the edges of and center the CCD imager chip within the annulus, and a silicon top wafer micro-machined as an annulus having cantilevered membranes which extend over the top of the CCD imager chip. The micro-machined silicon wafers are stacked in the order given above with the CCD imager chip centered in the center wafer and sandwiched between the base and top wafers. The thickness of the center wafer is about 20% less than the thickness of the CCD imager chip. Preferably, four titanium wires, each grasping the edges of the top and base wafers, compress all three wafers together, flexing the cantilever fingers of the top wafer to accommodate the thickness of the CCD imager chip, acting as a spring holding the CCD imager chip in place.

In Vivo Tracking of Mesechymal Stem Cells Using Fluorescent Nanoparticles in an Osteochondral Repair Model

PubMed Central

Lee, Jong Min; Kim, Byung-Soo; Lee, Haeshin; Im, Gun-Il

2012-01-01

We devised and tested an in vivo system to monitor the migration of mesenchymal stem cells (MSCs) within the marrow cavity. In vitro studies confirmed that platelet-derived growth factor (PDGF)-AA had the most potent chemotactic effect of the tested factors, and possessed the greatest number of receptors in MSCs. MSCs were labeled with fluorescent nanoparticles and injected into the marrow cavity of nude rats through osteochondral defects created in the distal femur. The defects were sealed with HCF (heparin-conjugated fibrin) or PDGF-AA-loaded HCF. In the HCF-only group, the nanoparticle-labeled MSCs dispersed outside the marrow cavity within 3 days after injection. In the PDGF-AA-loaded HCF group, the labeled cells moved time-dependently for 14 days toward the osteochondral defect. HCF-PDGF in low dose (LD; 8.5 ng/µl) was more effective than HCF-PDGF in high dose (HD; 17 ng/µl) in recruiting the MSCs to the osteochondral defect. After 21 days, the defects treated with PDGF and transforming growth factor (TGF)-β1-loaded HCF showed excellent cartilage repair compared with other groups. Further studies confirmed that this in vivo osteochondral MSCs tracking system (IOMTS) worked for other chemoattractants (chemokine (C-C motif) ligand 2 (CCL2) and PDGF-BB). IOMTS can provide a useful tool to examine the effect of growth factors or chemokines on endogenous cartilage repair. PMID:22491215

Restoration of a Critical Mandibular Bone Defect Using Human Alveolar Bone-Derived Stem Cells and Porous Nano-HA/Collagen/PLA Scaffold

PubMed Central

Wang, Xing; Xing, Helin; Zhang, Guilan; Wu, Xia; Zou, Xuan; Feng, Lin; Wang, Dongsheng; Li, Meng; Zhao, Jing; Du, Jianwei; Lv, Yan; E, Lingling; Liu, Hongchen

2016-01-01

Periodontal bone defects occur in a wide variety of clinical situations. Adult stem cell- and biomaterial-based bone tissue regeneration are a promising alternative to natural bone grafts. Recent evidence has demonstrated that two populations of adult bone marrow mesenchymal stromal cells (BMSCs) can be distinguished based on their embryonic origins. These BMSCs are not interchangeable, as bones preferentially heal using cells that share the same embryonic origin. However, the feasibility of tissue engineering using human craniofacial BMSCs was unclear. The goal of this study was to explore human craniofacial BMSC-based therapy for the treatment of localized mandibular defects using a standardized, minimally invasive procedure. The BMSCs' identity was confirmed. Scanning electron microscopy, a cell proliferation assay, and supernatant detection indicated that the nHAC/PLA provided a suitable environment for aBMSCs. Real-time PCR and electrochemiluminescence immunoassays demonstrated that osteogenic markers were upregulated by osteogenic preinduction. Moreover, in a rabbit critical-size mandibular bone defect model, total bone formation in the nHAC/PLA + aBMSCs group was significantly higher than in the nHAC/PLA group but significantly lower than in the nHAC/PLA + preinduced aBMSCs. These findings demonstrate that this engineered bone is a valid alternative for the correction of mandibular bone defects. PMID:27118977

Human intrabony defect regeneration with micro-grafts containing dental pulp stem cells: A randomized controlled clinical trial.

PubMed

Ferrarotti, Francesco; Romano, Federica; Gamba, Mara Noemi; Quirico, Andrea; Giraudi, Marta; Audagna, Martina; Aimetti, Mario

2018-05-19

The goal of this study was to evaluate if dental pulp stem cells (DPSCs) delivered into intrabony defects in a collagen scaffold would enhance the clinical and radiographic parameters of periodontal regeneration. In this randomized controlled trial, 29 chronic periodontitis patients presenting one deep intrabony defect and requiring extraction of one vital tooth were consecutively enrolled. Defects were randomly assigned to test or control treatments which both consisted of the use of minimally invasive surgical technique. The dental pulp of the extracted tooth was mechanically dissociated to obtain micro-grafts rich in autologous DPSCs. Test sites (n=15) were filled with micro-grafts seeded onto collagen sponge, whereas control sites (n=14) with collagen sponge alone. Clinical and radiographic parameters were recorded at baseline, 6 and 12 months postoperatively. Test sites exhibited significantly more PD reduction (4.9 mm versus 3.4 mm), CAL gain (4.5 versus 2.9 mm) and bone defect fill (3.9 versus 1.6 mm) than controls. Moreover, residual PD < 5 mm (93% versus 50%) and CAL gain ≥ 4 mm (73% versus 29%) was significantly more frequent in the test group. Application of DPSCs significantly improved clinical parameters of periodontal regeneration one year after treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Huanglongbing increases Diplodia Stem End Rot in Citrus sinensis

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), one of the most devastating diseases of citrus is caused by the a-Proteobacteria Candidatus Liberibacter. Diplodia natalensis Pole-Evans is a fungal pathogen which has been known to cause a postharvest stem-end rot of citrus, the pathogen infects citrus fruit under the calyx, an...

Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots

PubMed Central

Berninger, Markus T.; Wexel, Gabriele; Rummeny, Ernst J.; Imhoff, Andreas B.; Anton, Martina

2013-01-01

The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects is much more complex and a far greater surgical and therapeutic challenge. The damaged tissue does not only include the superficial cartilage layer but also the subchondral bone. For deep, osteochondral damage, as it occurs for example with osteochondrosis dissecans, the full thickness of the defect needs to be replaced to restore the joint surface 1. Eligible therapeutic procedures have to consider these two different tissues with their different intrinsic healing potential 2. In the last decades, several surgical treatment options have emerged and have already been clinically established 3-6. Autologous or allogeneic osteochondral transplants consist of articular cartilage and subchondral bone and allow the replacement of the entire osteochondral unit. The defects are filled with cylindrical osteochondral grafts that aim to provide a congruent hyaline cartilage covered surface 3,7,8. Disadvantages are the limited amount of available grafts, donor site morbidity (for autologous transplants) and the incongruence of the surface; thereby the application of this method is especially limited for large defects. New approaches in the field of tissue engineering opened up promising possibilities for regenerative osteochondral therapy. The implantation of autologous chondrocytes marked the first cell based biological approach for the treatment of full-thickness cartilage lesions and is now worldwide established with good clinical results even 10 to 20 years after implantation 9,10. However, to date, this technique is not suitable for the treatment of all types of lesions such as deep defects involving the subchondral bone 11. The sandwich-technique combines bone grafting with current approaches in Tissue Engineering 5,6. This combination seems to be able to overcome the limitations seen in osteochondral grafts alone. After autologous bone grafting to the subchondral defect area, a membrane seeded with autologous chondrocytes is sutured above and facilitates to match the topology of the graft with the injured site. Of course, the previous bone reconstruction needs additional surgical time and often even an additional surgery. Moreover, to date, long-term data is missing 12. Tissue Engineering without additional bone grafting aims to restore the complex structure and properties of native articular cartilage by chondrogenic and osteogenic potential of the transplanted cells. However, again, it is usually only the cartilage tissue that is more or less regenerated. Additional osteochondral damage needs a specific further treatment. In order to achieve a regeneration of the multilayered structure of osteochondral defects, three-dimensional tissue engineered products seeded with autologous/allogeneic cells might provide a good regeneration capacity 11. Beside autologous chondrocytes, mesenchymal stem cells (MSC) seem to be an attractive alternative for the development of a full-thickness cartilage tissue. In numerous preclinical in vitro and in vivo studies, mesenchymal stem cells have displayed excellent tissue regeneration potential 13,14. The important advantage of mesenchymal stem cells especially for the treatment of osteochondral defects is that they have the capacity to differentiate in osteocytes as well as chondrocytes. Therefore, they potentially allow a multilayered regeneration of the defect. In recent years, several scaffolds with osteochondral regenerative potential have therefore been developed and evaluated with promising preliminary results 1,15-18. Furthermore, fibrin glue as a cell carrier became one of the preferred techniques in experimental cartilage repair and has already successfully been used in several animal studies 19-21 and even first human trials 22. The following protocol will demonstrate an experimental technique for isolating mesenchymal stem cells from a rabbit's bone marrow, for subsequent proliferation in cell culture and for preparing a standardized in vitro-model for fibrin-cell-clots. Finally, a technique for the implantation of pre-established fibrin-cell-clots into artificial osteochondral defects of the rabbit's knee joint will be described. PMID:23728213

Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect.

PubMed

Kumar, Sanjay; Ponnazhagan, Selvarangan

2012-04-01

Although the number of mesenchymal stem cells (MSC) in the bone marrow is sufficient to maintain skeletal homeostasis, in osteopenic pathology, aggravated osteoclast activity or insufficient osteoblast numbers ensue, affecting normal bone remodeling. Most of the currently available therapies are anti-resorptive with limited osteogenic potential. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in tissue repair, amplification of endogenous stem cells may provide an alternative approach in these conditions. The present study determined the potential of MSC mobilization in vivo, using combinations of different growth factors with the CXCR4 antagonist, AMD3100, in a mouse model of segmental bone defect. Results indicated that among several factors tested IGF1 had maximum proliferative ability of MSC in vitro. Results of the in vivo studies indicated that the combination of IGF1 and AMD3100 provided significant augmentation of bone growth as determined by DXA, micro-CT and histomorphometry in mice bearing segmental fractures. Further, characterization of MSC isolated from mice treated with IGF1 and AMD3100 indicated Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways mediating this effect. These data indicate the potential of in vivo stem cell mobilization as a novel alternative for bone healing. Copyright © 2012 Elsevier Inc. All rights reserved.

Ku must load directly onto the chromosome end in order to mediate its telomeric functions.

PubMed

Lopez, Christopher R; Ribes-Zamora, Albert; Indiviglio, Sandra M; Williams, Christopher L; Haricharan, Svasti; Bertuch, Alison A

2011-08-01

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding-defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance.

Ku Must Load Directly onto the Chromosome End in Order to Mediate Its Telomeric Functions

PubMed Central

Lopez, Christopher R.; Ribes-Zamora, Albert; Indiviglio, Sandra M.; Williams, Christopher L.; Haricharan, Svasti; Bertuch, Alison A.

2011-01-01

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding–defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance. PMID:21852961

Micron-Scale Differential Scanning Calorimeter on a Chip

DOEpatents

Cavicchi, Richard E; Poirier, Gregory Ernest; Suehle, John S; Gaitan, Michael; Tea, Nim H

1998-06-30

A differential scanning microcalorimeter produced on a silicon chip enables microscopic scanning calorimetry measurements of small samples and thin films. The chip may be fabricated using standard CMOS processes. The microcalorimeter includes a reference zone and a sample zone. The reference and sample zones may be at opposite ends of a suspended platform or may reside on separate platforms. An integrated polysilicon heater provides heat to each zone. A thermopile consisting of a succession of thermocouple junctions generates a voltage representing the temperature difference between the reference and sample zones. Temperature differences between the zones provide information about the chemical reactions and phase transitions that occur in a sample placed in the sample zone.

Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

DTIC Science & Technology

2013-04-29

transduction of human mesenchymal stem cells (MSCs), BMP2 was not detectable by Western blotting, whereas high levels of the protein were produced by A549 (human... mesenchymal stem cells , generating high levels of BMP2. When Ad5BMP2 or Ad5F35BMP2 were compared in vitro for their ability to induce BMP2 synthesis...in human mesenchymal stem cells and in vivo for their ability to stimulate formation of heterotopic bone, mineralized bone was radiologically

[MR findings in patients with idiopathic panhypopituitarism].

PubMed

Fahrendorf, G; Brämswig, J; Bals-Pratsch, M

1990-05-01

High-resolution MR imaging was performed in seven patients with pituitary dwarfism and panhypopituitarism. In five cases MR-findings included absence of the infundibulum and of the normal intrasellar posterior pituitary bright spot, and the presence of a small nodule at the median eminence. The absence of diabetes insipidus in these patients and the signal characteristics of the nodule at the median eminence suggest that the latter may represent a functioning ectopic posterior pituitary lobe. This complex of findings was only observed in patients with complications in the perinatal period (breech delivery) and appears to be the end result of an ischemic or traumatic injury of the infundibular stem. The infundibular defect would explain both the permanent hormone deficiency of the anterior pituitary gland through a disruption of the hypothalamic-hypophyseal portal system and the absence of diabetes insipidus through an ectopic regeneration of the neurohypophysis at the median eminence.

In vivo investigation of tissue-engineered periosteum for the repair of allogeneic critical size bone defects in rabbits.

PubMed

Zhao, Lin; Zhao, Junli; Yu, Jiajia; Sun, Rui; Zhang, Xiaofeng; Hu, Shuhua

2017-04-01

The aim of the study was to evaluate the efficacy of tissue-engineered periosteum (TEP) in repairing allogenic bone defects in the long term. TEP was biofabricated with osteoinduced rabbit bone marrow mesenchymal stem cells and porcine small intestinal submucosa (SIS). A total of 24 critical sized defects were created bilaterally in radii of 12 New Zealand White rabbits. TEP/SIS was implanted into the defect site. Bone defect repair was evaluated with radiographic and histological examination at 4, 8 and 12 weeks. Bone defects were structurally reconstructed in the TEP group with mature cortical bone and medullary canals, however this was not observed in the SIS group at 12 weeks. The TEP approach can effectively restore allogenic critical sized defects, and achieve maturity of long-bone structure in 12 weeks in rabbit models.

Microtechnology in Space: NASA's Lab-on-a-Chip Applications Development Program

NASA Technical Reports Server (NTRS)

Monaco, Lisa; Spearing, Scott; Jenkins, Andy; Symonds, Wes; Mayer, Derek; Gouldie, Edd; Wainwright, Norm; Fries, Marc; Maule, Jake; Toporski, Jan

2004-01-01

NASA's Marshall Space Flight Center (MSFC) Lab on a Chip Application Development LOCAD) team has worked with microfluidic technology for the past few years in an effort to support NASA's Mission. In that time, such microfluidic based Lab-on-a-Chip (LOC) systems have become common technology in clinical and diagnostic laboratories. The approach is most attractive due to its highly miniaturized platform and ability to perform reagent handling (i-e., dilution, mixing, separation) and diagnostics for multiple reactions in an integrated fashion. LOCAD, along with Caliper Life Sciences has successfully developed the first LOC device for macromolecular crystallization using a workstation acquired specifically for designing custom chips, the Caliper 42. LOCAD uses this, along with a novel MSFC-designed and built workstation for microfluidic development. The team has a cadre of LOC devices that can be used to perform initial feasibility testing to determine the efficacy of the LOC approach for a specific application. Once applicability has been established, the LOCAD team, along with the Army's Aviation and Missile Command microfabrication facility, can then begin to custom design and fabricate a device per the user's specifications. This presentation will highlight the LOCAD team's proven and unique expertise that has been utilized to provide end to end capabilities associated with applying microfluidics for applications that include robotic life detection instrumentation, crew health monitoring and microbial and environmental monitoring for human Exploration.

Chip-to-chip optical link by using optical wiring method

NASA Astrophysics Data System (ADS)

Cho, In-Kui; Ahn, Seoung Ho; Jeong, Myung-Yung; Rho, Byung Sup; Park, Hyo Hoon

2008-01-01

A practical optical link system was prepared with a transmitter (Tx) and receiver (Rx). The optical TRx module consisted of a metal optical bench, a module printed circuit board (PCB), a driver/receiver IC, a VCSEL/PD array, and an optical link block composed of plastic optical fiber (POF). For the optical interconnection between the light-sources and detectors, an optical wiring method has been proposed to enable easy assembly. This paper provides a method for optical interconnection between an optical Tx and an optical Rx, comprising the following steps: (a) forming a light source device, an optical detection device, and an optical transmission unit on a substrate (metal optical bench (MOB)); (b) preparing a flexible optical transmission-connection medium (optical wiring link) to optically connect the light source device formed on the substrate with the optical detection device; and (c) directly connecting one end of the surface-finished optical transmission connection medium with the light source device and the other end with the optical detection device. A chip-to-chip optical link system constructed with TRx modules was fabricated and the optical characteristics were measured. The results clearly demonstrate that the use of an optical wiring method can provide robust and cost-effective assembly for vertical-cavity surface-emitting lasers (VCSELs) and photodiodes (PDs). We successfully achieved a 5 Gb/s data transmission rate with this optical link.

An accessible micro-capillary electrophoresis device using surface-tension-driven flow

PubMed Central

Mohanty, Swomitra K.; Warrick, Jay; Gorski, Jack; Beebe, David J.

2010-01-01

We present a rapidly fabricated micro-capillary electrophoresis chip that utilizes surface-tension-driven flow for sample injection and extraction of DNA. Surface-tension-driven flow (i.e. passive pumping) injects a fixed volume of sample that can be predicted mathematically. Passive pumping eliminates the need for tubing, valves, syringe pumps, and other equipment typically needed for interfacing with microelectrophoresis chips. This method requires a standard micropipette to load samples before separation, and remove the resulting bands after analysis. The device was made using liquid phase photopolymerization to rapidly fabricate the chip without the need of special equipment typically associated with the construction of microelectrophoresis chips (e.g. cleanroom). Batch fabrication time for the device presented here was 1.5 h including channel coating time to suppress electroosmotic flow. Devices were constructed out of poly-isobornyl acrylate and glass. A standard microscope with a UV source was used for sample detection. Separations were demonstrated using Promega BenchTop 100 bp ladder in hydroxyl ethyl cellulose (HEC) and oligonucleotides of 91 and 118 bp were used to characterize sample injection and extraction of DNA bands. The end result was an inexpensive micro-capillary electrophoresis device that uses tools (e.g. micropipette, electrophoretic power supplies, and microscopes) already present in most labs for sample manipulation and detection, making it more accessible for potential end users. PMID:19425002

Global fit concept in revision hip arthroplasty for cementless press-fit femoral stems.

PubMed

Canovas, F; LeBeguec, P; Batard, J; Gaillard, F; Dagneaux, L

2017-06-01

A revision stem may be required after a femoral extended trochanteric osteotomy (ETO) is made during revision hip arthroplasty. The two main complications of straight cementless femoral stems are subsidence due to inadequate osteointegration and stress-shielding. We will describe an original revision method with ETO that uses a straight cementless stem. The goal of this method was to achieve the most extensive press-fit possible during stem implantation to improve the transmission of stresses to the bone and to prevent reduction in bone density. The intramedullary preparation was done after closure and fixation of the ETO, which allows impaction of the revision stem with metaphyseal and diaphyseal press-fit. We report encouraging results with preservation of periprosthetic bone stock and good osteointegration of these revision stems at the final follow-up. Pronounced sagittal curvature or large bone defects are contraindications for this technique. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Photographic guide to selected external defect indicators and associated internal defects in black cherry

Treesearch

Everette D. Rast; John A. Beaton; John A. Beaton

1985-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development for black cherry. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in yellow birch

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow birch. Eleven types of external...

Photographic guide of selected external defect indicators and associated internal defects in sugar maple

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for sugar maple. Eleven types of external...

Photographic guide to selected external defect indicators and associated internal defects in black walnut

Treesearch

Everette D.Beaton John A. Rast; David L. Sonderman; David L. Sonderman

1988-01-01

To properly classify qr grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its develqpment for black walnut. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in white oak

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman; David L. Sonderman

1989-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development for white oak. It illustrates and...

Photographic guide of selected external defect indicators and associated internal defects in yellow-poplar

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow-poplar. Twelve types of external...

Photographic guide of selected external defect indicators and associated internal defects in northern red oak

Treesearch

Everette D. Rast

1982-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide aids the individual in identifying the surface defect indicator and also shows the progressive stages of the defect throughout its development. It illustrates and describes eight types...

Global loss of Leucine Carboxyl Methyltransferase-1 causes severe defects in fetal liver hematopoiesis.

PubMed

Lee, Jocelyn A; Wang, Zhengqi; Sambo, Danielle; Bunting, Kevin D; Pallas, David C

2018-05-07

Leucine Carboxyl Methyltransferase-1 (LCMT-1) 3 methylates the carboxy-terminal leucine α-carboxyl group of the catalytic subunits of the protein phosphatase 2A (PP2A) subfamily of protein phosphatases, PP2Ac, PP4c, and PP6c. LCMT-1 differentially regulates the formation and function of a subset of the heterotrimeric complexes that PP2A and PP4 form with their regulatory subunits. Global LCMT-1 knockout causes embryonic lethality in mice, but LCMT-1 function in development is unknown. In the current study, we analyzed the effects of global LCMT-1 loss on embryonic development. LCMT-1 knockout causes loss of PP2Ac methylation, indicating that LCMT-1 is the sole PP2Ac methyltransferase. PP2A heterotrimers containing the Bα and Bδ B-type subunits are dramatically reduced in whole embryos, and the steady-state levels of PP2Ac and the PP2A structural A subunit are also down ~30%. Strikingly, global loss of LCMT-1 causes severe defects in fetal hematopoiesis and death by embryonic day 16.5 (E16.5). Fetal livers of homozygous lcmt-1 knockout embryos display hypocellularity, elevated apoptosis, and greatly reduced numbers of hematopoietic stem and progenitor cell-enriched Kit + Lin - Sca1 + (KLS) cells. The percent cycling cells and mitotic indexes of wild-type and lcmt-1 knockout fetal liver cells are similar, suggesting that hypocellularity may be due to a combination of apoptosis and/or defects in specification, self-renewal, or survival of stem cells. Indicative of a possible intrinsic defect in stem cells, non-competitive and competitive transplantation experiments reveal that lcmt-1 loss causes a severe multi-lineage hematopoietic repopulating defect. Therefore, this study reveals a novel role for LCMT-1 as a key player in fetal liver hematopoiesis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Self-Renewal of Single Mouse Hematopoietic Stem Cells Is Reduced by JAK2V617F Without Compromising Progenitor Cell Expansion

PubMed Central

Kent, David G.; Li, Juan; Tanna, Hinal; Fink, Juergen; Kirschner, Kristina; Pask, Dean C.; Silber, Yvonne; Hamilton, Tina L.; Sneade, Rachel; Simons, Benjamin D.; Green, Anthony R.

2013-01-01

Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F subclinical clonal expansions and the transition to overt MPNs will illuminate the earliest stages of tumor establishment and subclone competition, fundamentally shifting the way we treat and manage cancers. PMID:23750118

Concept Design for a 1-Lead Wearable/Implantable ECG Front-End: Power Management

PubMed Central

George, Libin; Gargiulo, Gaetano Dario; Lehmann, Torsten; Hamilton, Tara Julia

2015-01-01

Power supply quality and stability are critical for wearable and implantable biomedical applications. For this reason we have designed a reconfigurable switched-capacitor DC-DC converter that, aside from having an extremely small footprint (with an active on-chip area of only 0.04 mm2), uses a novel output voltage control method based upon a combination of adaptive gain and discrete frequency scaling control schemes. This novel DC-DC converter achieves a measured output voltage range of 1.0 to 2.2 V with power delivery up to 7.5 mW with 75% efficiency. In this paper, we present the use of this converter as a power supply for a concept design of a wearable (15 mm × 15 mm) 1-lead ECG front-end sensor device that simultaneously harvests power and communicates with external receivers when exposed to a suitable RF field. Due to voltage range limitations of the fabrication process of the current prototype chip, we focus our analysis solely on the power supply of the ECG front-end whose design is also detailed in this paper. Measurement results show not just that the power supplied is regulated, clean and does not infringe upon the ECG bandwidth, but that there is negligible difference between signals acquired using standard linear power-supplies and when the power is regulated by our power management chip. PMID:26610497

MEDUSA-32: A low noise, low power silicon strip detector front-end electronics, for space applications

NASA Astrophysics Data System (ADS)

Cicuttin, Andres; Colavita, Alberto; Cerdeira, Alberto; Fratnik, Fabio; Vacchi, Andrea

1997-02-01

In this report we describe a mixed analog-digital integrated circuit (IC) designed as the front-end electronics for silicon strip-detectors for space applications. In space power consumption, compactness and robustness become critical constraints for a pre-amplifier design. The IC is a prototype with 32 complete channels, and it is intended for a large area particle tracker of a new generation of gamma ray telescopes. Each channel contains a charge sensitive amplifier, a pulse shaper, a discriminator and two digital buffers. The reference trip point of the discriminator is adjustable. This chip also has a custom PMOSFET transistor per channel, included in order to provide the high dynamic resistance needed to reverse-bias the strip diode. The digital part of the chip is used to store and serially shift out the state of the channels. There is also a storage buffer that allows the disabling of non-functioning channels if it is required by the data acquisition system. An input capacitance of 30 pF introduced at the input of the front-end produces less than 1000 electrons of RMS equivalent noise charge (ENC), for a total power dissipation of only 60 μW per channel. The chip was made using Orbit's 1.2 μm double poly, double metal n-well low noise CMOS process. The dimensions of the IC are 2400 μm × 8840 μm.

Concept Design for a 1-Lead Wearable/Implantable ECG Front-End: Power Management.

PubMed

George, Libin; Gargiulo, Gaetano Dario; Lehmann, Torsten; Hamilton, Tara Julia

2015-11-19

Power supply quality and stability are critical for wearable and implantable biomedical applications. For this reason we have designed a reconfigurable switched-capacitor DC-DC converter that, aside from having an extremely small footprint (with an active on-chip area of only 0.04 mm²), uses a novel output voltage control method based upon a combination of adaptive gain and discrete frequency scaling control schemes. This novel DC-DC converter achieves a measured output voltage range of 1.0 to 2.2 V with power delivery up to 7.5 mW with 75% efficiency. In this paper, we present the use of this converter as a power supply for a concept design of a wearable (15 mm × 15 mm) 1-lead ECG front-end sensor device that simultaneously harvests power and communicates with external receivers when exposed to a suitable RF field. Due to voltage range limitations of the fabrication process of the current prototype chip, we focus our analysis solely on the power supply of the ECG front-end whose design is also detailed in this paper. Measurement results show not just that the power supplied is regulated, clean and does not infringe upon the ECG bandwidth, but that there is negligible difference between signals acquired using standard linear power-supplies and when the power is regulated by our power management chip.

A Front-End Electronics Prototype Based on Gigabit Ethernet for the ATLAS Small-Strip Thin Gap Chamber

NASA Astrophysics Data System (ADS)

Hu, Kun; Lu, Houbing; Wang, Xu; Li, Feng; Wang, Xinxin; Geng, Tianru; Yang, Hang; Liu, Shengquan; Han, Liang; Jin, Ge

2017-06-01

A front-end electronics prototype for the ATLAS small-strip Thin Gap Chamber (sTGC) based on gigabit Ethernet has been developed. The prototype is designed to read out signals of pads, wires, and strips of the sTGC detector. The prototype includes two VMM2 chips developed to read out the signals of the sTGC, a Xilinx Kintex-7 field-programmable gate array (FPGA) used for the VMM2 configuration and the events storage, and a gigabit Ethernet transceiver PHY chip for interfacing with a computer. The VMM2 chip is designed for the readout of the Micromegas detector and sTGC detector, which is composed of 64 linear front-end channels. Each channel integrates a charge-sensitive amplifier, a shaper, several analog-to-digital converters, and other digital functions. For a bunch-crossing interval of 25 ns, events are continuously read out by the FPGA and forwarded to the computer. The interface between the computer and the prototype has been measured to reach an error-free rate of 900 Mb/s, therefore making a very effective use of the available bandwidth. Additionally, the computer can control several prototypes of this kind simultaneously via the Ethernet interface. At present, the prototype will be used for the sTGC performance test. The features of the prototype are described in detail.

Single event effect hardness for the front-end ASICs in the DAMPE satellite BGO calorimeter

NASA Astrophysics Data System (ADS)

Gao, Shan-Shan; Jiang, Di; Feng, Chang-Qing; Xi, Kai; Liu, Shu-Bin; An, Qi

2016-01-01

The Dark Matter Particle Explorer (DAMPE) is a Chinese scientific satellite designed for cosmic ray studies with a primary scientific goal of indirect detection of dark matter particles. As a crucial sub-detector, the BGO calorimeter measures the energy spectrum of cosmic rays in the energy range from 5 GeV to 10 TeV. In order to implement high-density front-end electronics (FEE) with the ability to measure 1848 signals from 616 photomultiplier tubes on the strictly constrained satellite platform, two kinds of 32-channel front-end ASICs, VA160 and VATA160, are customized. However, a space mission period of more than 3 years makes single event effects (SEEs) become threats to reliability. In order to evaluate SEE sensitivities of these chips and verify the effectiveness of mitigation methods, a series of laser-induced and heavy ion-induced SEE tests were performed. Benefiting from the single event latch-up (SEL) protection circuit for power supply, the triple module redundancy (TMR) technology for the configuration registers and the optimized sequential design for the data acquisition process, 52 VA160 chips and 32 VATA160 chips have been applied in the flight model of the BGO calorimeter with radiation hardness assurance. Supported by Strategic Priority Research Program on Space Science of the Chinese Academy of Sciences (XDA04040202-4) and Fundamental Research Funds for the Central Universities (WK2030040048)

Single Molecule Investigation of Kinesin-1 Motility Using Engineered Microtubule Defects

NASA Astrophysics Data System (ADS)

Gramlich, Michael W.; Conway, Leslie; Liang, Winnie H.; Labastide, Joelle A.; King, Stephen J.; Xu, Jing; Ross, Jennifer L.

2017-03-01

The structure of the microtubule is tightly regulated in cells via a number of microtubule associated proteins and enzymes. Microtubules accumulate structural defects during polymerization, and defect size can further increase under mechanical stresses. Intriguingly, microtubule defects have been shown to be targeted for removal via severing enzymes or self-repair. The cell’s control in defect removal suggests that defects can impact microtubule-based processes, including molecular motor-based intracellular transport. We previously demonstrated that microtubule defects influence cargo transport by multiple kinesin motors. However, mechanistic investigations of the observed effects remained challenging, since defects occur randomly during polymerization and are not directly observable in current motility assays. To overcome this challenge, we used end-to-end annealing to generate defects that are directly observable using standard epi-fluorescence microscopy. We demonstrate that the annealed sites recapitulate the effects of polymerization-derived defects on multiple-motor transport, and thus represent a simple and appropriate model for naturally-occurring defects. We found that single kinesins undergo premature dissociation, but not preferential pausing, at the annealed sites. Our findings provide the first mechanistic insight to how defects impact kinesin-based transport. Preferential dissociation on the single-molecule level has the potential to impair cargo delivery at locations of microtubule defect sites in vivo.

Highly specific detection of genetic modification events using an enzyme-linked probe hybridization chip.

PubMed

Zhang, M Z; Zhang, X F; Chen, X M; Chen, X; Wu, S; Xu, L L

2015-08-10

The enzyme-linked probe hybridization chip utilizes a method based on ligase-hybridizing probe chip technology, with the principle of using thio-primers for protection against enzyme digestion, and using lambda DNA exonuclease to cut multiple PCR products obtained from the sample being tested into single-strand chains for hybridization. The 5'-end amino-labeled probe was fixed onto the aldehyde chip, and hybridized with the single-stranded PCR product, followed by addition of a fluorescent-modified probe that was then enzymatically linked with the adjacent, substrate-bound probe in order to achieve highly specific, parallel, and high-throughput detection. Specificity and sensitivity testing demonstrated that enzyme-linked probe hybridization technology could be applied to the specific detection of eight genetic modification events at the same time, with a sensitivity reaching 0.1% and the achievement of accurate, efficient, and stable results.

Validation and Interrogation of Differentially Expressed and Alternatively Spliced Genes in African American Prostate Cancer

DTIC Science & Technology

2016-10-01

These analyses have led to two submitted manuscripts. The first manuscript, “Variants of stemness -related genes predicted to regulate RNA splicing...and Table 1-3 at the end of this progress report. The second manuscript, “Single nucleotide polymorphisms of stemness pathway genes predicted to...cancer and support a contribution of the stemness pathway to prostate cancer patient outcome. Please see Figure 5-7 and Table 4-6 at the end of this

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

PubMed

Saito, Akiko; Ooki, Akio; Nakamura, Takashi; Onodera, Shoko; Hayashi, Kamichika; Hasegawa, Daigo; Okudaira, Takahito; Watanabe, Katsuhito; Kato, Hiroshi; Onda, Takeshi; Watanabe, Akira; Kosaki, Kenjiro; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakamoto, Teruo; Yamaguchi, Akira; Sueishi, Kenji; Azuma, Toshifumi

2018-01-22

Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

Novel application of stem cell-derived factors for periodontal regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp; Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp; Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp

Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, andmore » hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.« less

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions.

PubMed

Schmal, Hagen; Kowal, Justyna M; Kassem, Moustapha; Seidenstuecker, Michael; Bernstein, Anke; Böttiger, Katharina; Xiong, Tanshiyue; Südkamp, Norbert P; Kubosch, Eva J

2018-01-01

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes ( p < 0.05). This correlated with a more chondrogenic structure and higher proteoglycan expression, resulting in a lower OARSI score ( p < 0.05). The repair tissue of all groups expressed comparable amounts of the collagen types I, II, and X. Cartilage regeneration following matrix-associated implantation using allogenic undifferentiated synovium-derived stem cells in a defect model in rabbits showed similar macroscopic results and collagen composition compared to amplified chondrocytes; however, biomechanical characteristics and histological scoring were inferior.

Polyglycolic acid-hyaluronan scaffolds loaded with bone marrow-derived mesenchymal stem cells show chondrogenic differentiation in vitro and cartilage repair in the rabbit model.

PubMed

Patrascu, Jenel M; Krüger, Jan Philipp; Böss, Hademar G; Ketzmar, Anna-Katharina; Freymann, Undine; Sittinger, Michael; Notter, Michael; Endres, Michaela; Kaps, Christian

2013-10-01

In cartilage repair, scaffold-assisted one-step approaches are used to improve the microfracture (Mfx) technique. Since the number of progenitors in Mfx is low and may further decrease with age, aim of our study was to analyze the chondrogenic potential of freeze-dried polyglycolic acid-hyaluronan (PGA-HA) implants preloaded with mesenchymal stem cells (MSCs) in vitro and in a rabbit articular cartilage defect model. Human bone marrow-derived MSC from iliac crest were cultured in freeze-dried PGA-HA implants for chondrogenic differentiation. In a pilot study, implants were loaded with autologous rabbit MSC and used to cover 5 mm × 6 mm full-thickness femoral articular cartilage defects (n = 4). Untreated defects (n = 3) served as controls. Gene expression analysis and histology showed induction of typical chondrogenic marker genes like type II collagen and formation of hyaline-like cartilaginous tissue in MSC-laden PGA-HA implants. Histological evaluation of rabbit repair tissue formation after 30 and 45 days showed formation of repair tissue, rich in chondrocytic cells and of a hyaline-like appearance. Controls showed no articular resurfacing, tissue repair in the subchondral zone and fibrin formation. These results suggest that MSC-laden PGA-HA scaffolds have chondrogenic potential and are a promising option for stem cell-mediated cartilage regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

PubMed Central

Kowal, Justyna M.; Seidenstuecker, Michael; Bernstein, Anke; Böttiger, Katharina; Xiong, Tanshiyue; Südkamp, Norbert P.

2018-01-01

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p < 0.05). This correlated with a more chondrogenic structure and higher proteoglycan expression, resulting in a lower OARSI score (p < 0.05). The repair tissue of all groups expressed comparable amounts of the collagen types I, II, and X. Cartilage regeneration following matrix-associated implantation using allogenic undifferentiated synovium-derived stem cells in a defect model in rabbits showed similar macroscopic results and collagen composition compared to amplified chondrocytes; however, biomechanical characteristics and histological scoring were inferior. PMID:29765410

Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair

PubMed Central

Ikeya, Makoto; Yasui, Yukihiko; Ikeda, Yasutoshi; Ebina, Kosuke; Moriguchi, Yu; Shimomura, Kazunori; Hideki, Yoshikawa

2017-01-01

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage. PMID:28607560

Arbitrary photonic wave plate operations on chip: Realizing Hadamard, Pauli-X, and rotation gates for polarisation qubits

PubMed Central

Heilmann, René; Gräfe, Markus; Nolte, Stefan; Szameit, Alexander

2014-01-01

Chip-based photonic quantum computing is an emerging technology that promises much speedup over conventional computers at small integration volumes. Particular interest is thereby given to polarisation-encoded photonic qubits, and many protocols have been developed for this encoding. However, arbitrary wave plate operation on chip are not available so far, preventing from the implementation of integrated universal quantum computing algorithms. In our work we close this gap and present Hadamard, Pauli-X, and rotation gates of high fidelity for photonic polarisation qubits on chip by employing a reorientation of the optical axis of birefringent waveguides. The optical axis of the birefringent waveguide is rotated due to the impact of an artificial stress field created by an additional modification close to the waveguide. By adjusting this length of the defect along the waveguide, the retardation between ordinary and extraordinary field components is precisely tunable including half-wave plate and quarter-wave plate operations. Our approach demonstrates the full range control of orientation and strength of the induced birefringence and thus allows arbitrary wave plate operations without affecting the degree of polarisation or introducing additional losses to the waveguides. The implemented gates are tested with classical and quantum light. PMID:24534893

Building up STEM: An Analysis of Teacher-Developed Engineering Design-Based STEM Integration Curricular Materials

ERIC Educational Resources Information Center

Guzey, S. Selcen; Moore, Tamara J.; Harwell, Michael

2016-01-01

Improving K-12 Science, Technology, Engineering, and Mathematics (STEM) education has a priority on numerous education reforms in the United States. To that end, developing and sustaining quality programs that focus on integrated STEM education is critical for educators. Successful implementation of any STEM program is related to the curriculum…

Jumping on the STEM Bandwagon: How Middle Grades Students and Teachers Can Benefit from STEM Experiences

ERIC Educational Resources Information Center

Lesseig, Kristin; Slavit, David; Nelson, Tamara Holmlund

2017-01-01

Given the current emphasis on science, technology, engineering, and math (STEM) education and its key attributes, middle school is an optimal time to implement STEM-based curricula. However, the interdisciplinary and open-ended nature of STEM projects often makes implementation difficult. In this article, we describe a professional development…

Therapeutic potential of dental stem cells

PubMed Central

Chalisserry, Elna Paul; Nam, Seung Yun; Park, Sang Hyug; Anil, Sukumaran

2017-01-01

Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies. The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart. The concept of developing tooth banking and preservation of dental stem cells is promising. Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run. PMID:28616151

On-chip Magnetic Separation and Cell Encapsulation in Droplets†

PubMed Central

Chen, Aaron; Byvank, Tom; Chang, Woo-Jin; Bharde, Atul; Vieira, Greg; Miller, Brandon; Chalmers, Jeffrey J.; Bashir, Rashid; Sooryakumar, Ratnasingham

2014-01-01

The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment would prevent cross-contamination, provide high recovery yield, and enable study of biological traits at a single cell level. These advantages of on-chip biological experiments is a significant improvement for myriad of cell analyses over conventional methods, which require bulk samples providing only averaged information on cell metabolism. We report on a device that integrates mobile magnetic trap array with microfluidic technology to provide, combined functionality of separation of immunomagnetically labeled cells or magnetic beads and their encapsulation with reagents into pico-liter droplets. This scheme of simultaneous reagent delivery and compartmentalization of the cells immediately after sorting, all performed seamlessly within the same chip, offers unique advantages such as the ability to capture cell traits as originated from its native environment, reduced chance of contamination, minimal use and freshness of the reagent solution that reacts only with separated objects, and tunable encapsulation characteristics independent of the input flow. In addition to the demonstrated preliminary cell viability assay, the device can potentially be integrated with other up- or downstream on-chip modules to become a powerful single-cell analysis tool. PMID:23370785

Phonon Networks with Silicon-Vacancy Centers in Diamond Waveguides

NASA Astrophysics Data System (ADS)

Lemonde, M.-A.; Meesala, S.; Sipahigil, A.; Schuetz, M. J. A.; Lukin, M. D.; Loncar, M.; Rabl, P.

2018-05-01

We propose and analyze a novel realization of a solid-state quantum network, where separated silicon-vacancy centers are coupled via the phonon modes of a quasi-one-dimensional diamond waveguide. In our approach, quantum states encoded in long-lived electronic spin states can be converted into propagating phonon wave packets and be reabsorbed efficiently by a distant defect center. Our analysis shows that under realistic conditions, this approach enables the implementation of high-fidelity, scalable quantum communication protocols within chip-scale spin-qubit networks. Apart from quantum information processing, this setup constitutes a novel waveguide QED platform, where strong-coupling effects between solid-state defects and individual propagating phonons can be explored at the quantum level.

Phonon Networks with Silicon-Vacancy Centers in Diamond Waveguides.

PubMed

Lemonde, M-A; Meesala, S; Sipahigil, A; Schuetz, M J A; Lukin, M D; Loncar, M; Rabl, P

2018-05-25

We propose and analyze a novel realization of a solid-state quantum network, where separated silicon-vacancy centers are coupled via the phonon modes of a quasi-one-dimensional diamond waveguide. In our approach, quantum states encoded in long-lived electronic spin states can be converted into propagating phonon wave packets and be reabsorbed efficiently by a distant defect center. Our analysis shows that under realistic conditions, this approach enables the implementation of high-fidelity, scalable quantum communication protocols within chip-scale spin-qubit networks. Apart from quantum information processing, this setup constitutes a novel waveguide QED platform, where strong-coupling effects between solid-state defects and individual propagating phonons can be explored at the quantum level.

PI3K/Akt-dependent functions of TFII-I transcription factors in mouse embryonic stem cells.

PubMed

Chimge, Nyam-Osor; Makeyev, Aleksandr V; Waigel, Sabine J; Enkhmandakh, Badam; Bayarsaihan, Dashzeveg

2012-04-01

Activation of PI3K/Akt signaling is sufficient to maintain the pluripotency of mouse embryonic stem cells (mESC) and results in down-regulation of Gtf2i and Gtf2ird1 encoding TFII-I family transcription factors. To investigate how these genes might be involved in the process of embryonic stem cell differentiation, we performed expression microarray profiling of mESC upon inhibition of PI3K by LY294002. This analysis revealed significant alterations in expression of genes for specific subsets of chromatin-modifying enzymes. Surprisingly, genome-wide promoter ChIP-chip mapping indicated that the majority of differently expressed genes could be direct targets of TFII-I regulation. The data support the hypothesis that upregulation of TFII-I factors leads to activation of a specific group of developmental genes during mESC differentiation. © 2011 Wiley Periodicals, Inc.

A microfluidic circulatory system integrated with capillary-assisted pressure sensors.

PubMed

Chen, Yangfan; Chan, Ho Nam; Michael, Sean A; Shen, Yusheng; Chen, Yin; Tian, Qian; Huang, Lu; Wu, Hongkai

2017-02-14

The human circulatory system comprises a complex network of blood vessels interconnecting biologically relevant organs and a heart driving blood recirculation throughout this system. Recreating this system in vitro would act as a bridge between organ-on-a-chip and "body-on-a-chip" and advance the development of in vitro models. Here, we present a microfluidic circulatory system integrated with an on-chip pressure sensor to closely mimic human systemic circulation in vitro. A cardiac-like on-chip pumping system is incorporated in the device. It consists of four pumping units and passive check valves, which mimic the four heart chambers and heart valves, respectively. Each pumping unit is independently controlled with adjustable pressure and pump rate, enabling users to control the mimicked blood pressure and heartbeat rate within the device. A check valve is located downstream of each pumping unit to prevent backward leakage. Pulsatile and unidirectional flow can be generated to recirculate within the device by programming the four pumping units. We also report an on-chip capillary-assisted pressure sensor to monitor the pressure inside the device. One end of the capillary was placed in the measurement region, while the other end was sealed. Time-dependent pressure changes were measured by recording the movement of the liquid-gas interface in the capillary and calculating the pressure using the ideal gas law. The sensor covered the physiologically relevant blood pressure range found in humans (0-142.5 mmHg) and could respond to 0.2 s actuation time. With the aid of the sensor, the pressure inside the device could be adjusted to the desired range. As a proof of concept, human normal left ventricular and arterial pressure profiles were mimicked inside this device. Human umbilical vein endothelial cells (HUVECs) were cultured on chip and cells can respond to mechanical forces generated by arterial-like flow patterns.

Characterization of Transformation-Induced Defects in Nickel Titanium Shape Memory Alloys

NASA Astrophysics Data System (ADS)

Bowers, Matthew L.

Shape memory alloys have remarkable strain recovery properties that make them ideal candidates for many applications that include devices in the automotive, aerospace, medical, and MEMS industries. Although these materials are widely used today, their performance is hindered by poor dimensional stability resulting from cyclic degradation of the martensitic transformation behavior. This functional fatigue results in decreased work output and cyclic accumulation of permanent strain. To date, few studies have taken a fundamental approach to investigating the interaction between plasticity and martensite growth and propagation, which is vitally important to mitigating functional fatigue in future alloy development. The current work focuses on understanding the interplay of these deformation mechanisms in NiTi-based shape memory alloys under a variety of different thermomechanical test conditions. Micron-scale compression testing of NiTi shape memory alloy single crystals is undertaken in an effort to probe the mechanism of austenite dislocation generation. Mechanical testing is paired with post mortem defect analysis via diffraction contrast scanning transmission electron microscopy (STEM). Accompanied by micromechanics-based modeling of local stresses surrounding a martensite plate, these results demonstrate that the previously existing martensite and resulting austenite dislocation substructure are intimately related. A mechanism of transformation-induced dislocation generation is described in detail. A study of pure and load-biased thermal cycling of bulk polycrystalline NiTi is done for comparison of the transformation behavior and resultant defects to the stress-induced case. Post mortem and in situ STEM characterization demonstrate unique defect configurations in this test mode and STEM-based orientation mapping reveals local crystal rotation with increasing thermal cycles. Changes in both martensite and austenite microstructures are explored. The results for several different thermomechanical histories are discussed and a new mechanism of austenite grain refinement is proposed with support from ab initio calculations and crystallographic theory.

Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

PubMed

Guan, Junjie; Zhang, Jieyuan; Li, Haiyan; Zhu, Zhenzhong; Guo, Shangchun; Niu, Xin; Wang, Yang; Zhang, Changqing

2015-01-01

Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs) are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP), and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP) were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

Co-Seeding Human Endothelial Cells with Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells on Calcium Phosphate Scaffold Enhances Osteogenesis and Vascularization in Rats.

PubMed

Liu, Xian; Chen, Wenchuan; Zhang, Chi; Thein-Han, Wahwah; Hu, Kevin; Reynolds, Mark A; Bao, Chongyun; Wang, Ping; Zhao, Liang; Xu, Hockin H K

2017-06-01

A major challenge in repairing large bone defects with tissue-engineered constructs is the poor vascularization in the defect. The lack of vascular networks leads to insufficient oxygen and nutrients supply, which compromises the survival of seeded cells. To achieve favorable regenerative effects, prevascularization of tissue-engineered constructs by co-culturing of endothelial cells and bone cells is a promising strategy. The aim of this study was to investigate the effects of human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) co-cultured with human umbilical vein endothelial cells (HUVECs) for prevascularization of calcium phosphate cement (CPC) scaffold on bone regeneration in vivo for the first time. HUVECs co-cultured with hiPSC-MSCs formed microcapillary-like structures in vitro. HUVECs promoted mineralization of hiPSC-MSCs on CPC scaffolds. Four groups were tested in a cranial bone defect model in nude rats: (1) CPC scaffold alone (CPC control); (2) HUVEC-seeded CPC (CPC-HUVEC); (3) hiPSC-MSC-seeded CPC (CPC-hiPSC-MSC); and (4) HUVECs co-cultured with hiPSC-MSCs on CPC scaffolds (co-culture group). After 12 weeks, the co-culture group achieved the greatest new bone area percentage of 46.38% ± 3.8% among all groups (p < 0.05), which was more than four folds of the 10.61% ± 1.43% of CPC control. In conclusion, HUVECs co-cultured with hiPSC-MSCs substantially promoted bone regeneration. The novel construct of HUVECs co-cultured with hiPSC-MSCs delivered via CPC scaffolds is promising to enhance bone and vascular regeneration in orthopedic applications.

The osteo-inductive activity of bone-marrow-derived mononuclear cells resides within the CD14+ population and is independent of the CD34+ population.

PubMed

Henrich, D; Seebach, C; Verboket, R; Schaible, A; Marzi, I; Bonig, H

2018-03-06

Bone marrow mononuclear cells (BMC) seeded on a scaffold of β-tricalcium phosphate (β-TCP) promote bone healing in a critical-size femur defect model. Being BMC a mixed population of predominantly mature haematopoietic cells, which cell type(s) is(are) instrumental for healing remains elusive. Although clinical therapies using BMC are often dubbed as stem cell therapies, whether stem cells are relevant for the therapeutic effects is unclear and, at least in the context of bone repair, seems dubious. Instead, in light of the critical contribution of monocytes and macrophages to tissue development, homeostasis and injury repair, in the current study it was hypothesised that BMC-mediated bone healing derived from the stem cell population. To test this hypothesis, bone remodelling studies were performed in an established athymic rats critical-size femoral defect model, with β-TCP scaffolds augmented with complete BMC or BMC immunomagnetically depleted of stem cells (CD34+) or monocytes/macrophages (CD14+). Bone healing was assessed 8 weeks after transplantation. Compared to BMC-augmented controls, when CD14- BMC, but not CD34- BMC were transplanted into the bone defect, femora possessed dramatically decreased biomechanical stability and new bone formation was markedly reduced, as measured by histology. The degree of vascularisation did not differ between the two groups. It was concluded that the monocyte fraction within the BMC provided critical osteo-inductive cues during fracture healing. Which factors were responsible at the molecular levels remained elusive. However, this study marked a significant progress towards elucidating the mechanisms by which BMC elicit their therapeutic effects, at least in bone regeneration.

A front-end read out chip for the OPERA scintillator tracker

NASA Astrophysics Data System (ADS)

Lucotte, A.; Bondil, S.; Borer, K.; Campagne, J. E.; Cazes, A.; Hess, M.; de La Taille, C.; Martin-Chassard, G.; Raux, L.; Repellin, J. P.

2004-04-01

Multi-anode photomultipliers H7546 are used to readout signal from the OPERA Scintillator Tracker (CERN/SPSC 2000-028, SPSC/P318, LNGSP 25/2000; CERN/SPSC 2001-025, SPSC/M668, LNGS-EXP30/2001). A 32-channel front-end Read Out Chip prototype accommodating the H7546 has been designed at LAL. This device features a low-noise, variable gain preamplifier to correct for multi-anode non-uniformity, an auto-trigger capability 100% efficient at a 0.3 photo-electron, and a charge measurement extending over a large dynamic range [0-100] photo-electrons. In this article we describe the ASIC architecture that is being implemented for the Target Tracker in OPERA, with a special emphasis put on the designs and the measured performance.

Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems.

PubMed

Pamies, David; Bal-Price, Anna; Chesné, Christophe; Coecke, Sandra; Dinnyes, Andras; Eskes, Chantra; Grillari, Regina; Gstraunthaler, Gerhard; Hartung, Thomas; Jennings, Paul; Leist, Marcel; Martin, Ulrich; Passier, Robert; Schwamborn, Jens C; Stacey, Glyn N; Ellinger-Ziegelbauer, Heidrun; Daneshian, Mardas

2018-04-13

A major reason for the current reproducibility crisis in the life sciences is the poor implementation of quality control measures and reporting standards. Improvement is needed, especially regarding increasingly complex in vitro methods. Good Cell Culture Practice (GCCP) was an effort from 1996 to 2005 to develop such minimum quality standards also applicable in academia. This paper summarizes recent key developments in in vitro cell culture and addresses the issues resulting for GCCP, e.g. the development of induced pluripotent stem cells (iPSCs) and gene-edited cells. It further deals with human stem-cell-derived models and bioengineering of organo-typic cell cultures, including organoids, organ-on-chip and human-on-chip approaches. Commercial vendors and cell banks have made human primary cells more widely available over the last decade, increasing their use, but also requiring specific guidance as to GCCP. The characterization of cell culture systems including high-content imaging and high-throughput measurement technologies increasingly combined with more complex cell and tissue cultures represent a further challenge for GCCP. The increasing use of gene editing techniques to generate and modify in vitro culture models also requires discussion of its impact on GCCP. International (often varying) legislations and market forces originating from the commercialization of cell and tissue products and technologies are further impacting on the need for the use of GCCP. This report summarizes the recommendations of the second of two workshops, held in Germany in December 2015, aiming map the challenge and organize the process or developing a revised GCCP 2.0.

Towards on-chip integration of brain imaging photodetectors using standard CMOS process.

PubMed

Kamrani, Ehsan; Lesage, Frederic; Sawan, Mohamad

2013-01-01

The main effects of on-chip integration on the performance and efficiency of silicon avalanche photodiode (SiAPD) and photodetector front-end is addressed in this paper based on the simulation and fabrication experiments. Two different silicon APDs are fabricated separately and also integrated with a transimpedance amplifier (TIA) front-end using standard CMOS technology. SiAPDs are designed in p+/n-well structure with guard rings realized in different shapes. The TIA front-end has been designed using distributed-gain concept combined with resistive-feedback and common-gate topology to reach low-noise and high gain-bandwidth product (GBW) characteristics. The integrated SiAPDs show higher signal-to-noise ratio (SNR), sensitivity and detection efficiency comparing to the separate SiAPDs. The integration does not show a significant effect on the gain and preserves the low power consumption. Using APDs with p-well guard-ring is preferred due to the higher observed efficiency after integration.

Evaluating the Whitening and Microstructural Effects of a Novel Whitening Strip on Porcelain and Composite Dental Materials

PubMed Central

Takesh, Thair; Sargsyan, Anik; Lee, Matthew; Anbarani, Afarin; Ho, Jessica; Wilder-Smith, Petra

2017-01-01

Aims The aim of this project was to evaluate the effects of 2 different whitening strips on color, microstructure and roughness of tea stained porcelain and composite surfaces. Methods 54 porcelain and 72 composite chips served as samples for timed application of over-the-counter (OTC) test or control dental whitening strips. Chips were divided randomly into three groups of 18 porcelain and 24 composite chips each. Of these groups, 1 porcelain and 1 composite set served as controls. The remaining 2 groups were randomized to treatment with either Oral Essentials® Whitening Strips or Crest® 3D White Whitestrips™. Sample surface structure was examined by light microscopy, profilometry and Scanning Electron Microscopy (SEM). Additionally, a reflectance spectrophotometer was used to assess color changes in the porcelain and composite samples over 24 hours of whitening. Data points were analyzed at each time point using ANOVA. Results In the light microscopy and SEM images, no discrete physical defects were observed in any of the samples at any time points. However, high-resolution SEM images showed an appearance of increased surface roughness in all composite samples. Using profilometry, significantly increased post-whitening roughness was documented in the composite samples exposed to the control bleaching strips. Composite samples underwent a significant and equivalent shift in color following exposure to Crest® 3D White Whitestrips™ and Oral Essentials® Whitening Strips. Conclusions A novel commercial tooth whitening strip demonstrated a comparable beaching effect to a widely used OTC whitening strip. Neither whitening strip caused physical defects in the sample surfaces. However, the control strip caused roughening of the composite samples whereas the test strip did not. PMID:29226023

Recent lab-on-chip developments for novel drug discovery.

PubMed

Khalid, Nauman; Kobayashi, Isao; Nakajima, Mitsutoshi

2017-07-01

Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development. In this review, we report on the latest developments in fabrication methods and production methodologies to tailor LOC devices. A brief overview of scale-up strategies is also presented together with their potential applications in drug delivery and discovery. The impact of LOC devices on drug development and discovery has been extensively reviewed in the past. The current research focuses on fast and accurate detection of genomics, cell mutations and analysis, drug delivery, and discovery. The current research also differentiates the LOC devices into new terminology of microengineering, like organ-on-a-chip, stem cells-on-a-chip, human-on-a-chip, and body-on-a-chip. Key challenges will be the transfer of fabricated LOC devices from lab-scale to industrial large-scale production. Moreover, extensive toxicological studies are needed to justify the use of microfabricated drug delivery vehicles in biological systems. It will also be challenging to transfer the in vitro findings to suitable and promising in vivo models. WIREs Syst Biol Med 2017, 9:e1381. doi: 10.1002/wsbm.1381 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

A scalable self-priming fractal branching microchannel net chip for digital PCR.

PubMed

Zhu, Qiangyuan; Xu, Yanan; Qiu, Lin; Ma, Congcong; Yu, Bingwen; Song, Qi; Jin, Wei; Jin, Qinhan; Liu, Jinyu; Mu, Ying

2017-05-02

As an absolute quantification method at the single-molecule level, digital PCR has been widely used in many bioresearch fields, such as next generation sequencing, single cell analysis, gene editing detection and so on. However, existing digital PCR methods still have some disadvantages, including high cost, sample loss, and complicated operation. In this work, we develop an exquisite scalable self-priming fractal branching microchannel net digital PCR chip. This chip with a special design inspired by natural fractal-tree systems has an even distribution and 100% compartmentalization of the sample without any sample loss, which is not available in existing chip-based digital PCR methods. A special 10 nm nano-waterproof layer was created to prevent the solution from evaporating. A vacuum pre-packaging method called self-priming reagent introduction is used to passively drive the reagent flow into the microchannel nets, so that this chip can realize sequential reagent loading and isolation within a couple of minutes, which is very suitable for point-of-care detection. When the number of positive microwells stays in the range of 100 to 4000, the relative uncertainty is below 5%, which means that one panel can detect an average of 101 to 15 374 molecules by the Poisson distribution. This chip is proved to have an excellent ability for single molecule detection and quantification of low expression of hHF-MSC stem cell markers. Due to its potential for high throughput, high density, low cost, lack of sample and reagent loss, self-priming even compartmentalization and simple operation, we envision that this device will significantly expand and extend the application range of digital PCR involving rare samples, liquid biopsy detection and point-of-care detection with higher sensitivity and accuracy.

Cell chips as new tools for cell biology--results, perspectives and opportunities.

PubMed

Primiceri, Elisabetta; Chiriacò, Maria Serena; Rinaldi, Ross; Maruccio, Giuseppe

2013-10-07

Cell culture technologies were initially developed as research tools for studying cell functions, but nowadays they are essential for the biotechnology industry, with rapidly expanding applications requiring more and more advancements with respect to traditional tools. Miniaturization and integration of sensors and microfluidic components with cell culture techniques open the way to the development of cellomics as a new field of research targeting innovative analytic platforms for high-throughput studies. This approach enables advanced cell studies under controllable conditions by providing inexpensive, easy-to-operate devices. Thanks to their numerous advantages cell-chips have become a hotspot in biosensors and bioelectronics fields and have been applied to very different fields. In this review exemplary applications will be discussed, for cell counting and detection, cytotoxicity assays, migration assays and stem cell studies.

[Preliminary investigation of treatment of ulnar nerve defect by end-to-side neurorrhaphy].

PubMed

Luo, Y; Wang, T; Fang, H

1997-11-01

In the repair of the defect of peripheral nerve, it was necessary to find an operative method with excellent therapeutic effect but simple technique. Based on the experimental study, one case of old injury of the ulnar nerve was treated by end-to-side neurorraphy with the intact median nerve. In this case the nerve defect was over 3 cm and unable to be sutured directly. The patient was followed up for fourteen months after the operation. The recovery of the sensation and the myodynamia was evaluated. The results showed that: the sensation and the motor function innervated by ulnar nerve were recovered. The function of the hand was almost recovered to be normal. It was proved that the end-to-side neurorraphy between the distal stump with the intact median nerve to repair the defect of the ulnar nerve was a new operative procedure for nerve repair. Clinically it had good effect with little operative difficulty. This would give a bright prospect to repair of peripheral nerve defect in the future.

Scaling and automation of a high-throughput single-cell-derived tumor sphere assay chip.

PubMed

Cheng, Yu-Heng; Chen, Yu-Chih; Brien, Riley; Yoon, Euisik

2016-10-07

Recent research suggests that cancer stem-like cells (CSCs) are the key subpopulation for tumor relapse and metastasis. Due to cancer plasticity in surface antigen and enzymatic activity markers, functional tumorsphere assays are promising alternatives for CSC identification. To reliably quantify rare CSCs (1-5%), thousands of single-cell suspension cultures are required. While microfluidics is a powerful tool in handling single cells, previous works provide limited throughput and lack automatic data analysis capability required for high-throughput studies. In this study, we present the scaling and automation of high-throughput single-cell-derived tumor sphere assay chips, facilitating the tracking of up to ∼10 000 cells on a chip with ∼76.5% capture rate. The presented cell capture scheme guarantees sampling a representative population from the bulk cells. To analyze thousands of single-cells with a variety of fluorescent intensities, a highly adaptable analysis program was developed for cell/sphere counting and size measurement. Using a Pluronic® F108 (poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)) coating on polydimethylsiloxane (PDMS), a suspension culture environment was created to test a controversial hypothesis: whether larger or smaller cells are more stem-like defined by the capability to form single-cell-derived spheres. Different cell lines showed different correlations between sphere formation rate and initial cell size, suggesting heterogeneity in pathway regulation among breast cancer cell lines. More interestingly, by monitoring hundreds of spheres, we identified heterogeneity in sphere growth dynamics, indicating the cellular heterogeneity even within CSCs. These preliminary results highlight the power of unprecedented high-throughput and automation in CSC studies.

The Children's Health Insurance Program Reauthorization Act Evaluation Findings on Children's Health Insurance Coverage in an Evolving Health Care Landscape.

PubMed

Harrington, Mary E

2015-01-01

The Children's Health Insurance Program (CHIP) Reauthorization Act (CHIPRA) reauthorized CHIP through federal fiscal year 2019 and, together with provisions in the Affordable Care Act, federal funding for the program was extended through federal fiscal year 2015. Congressional action is required or federal funding for the program will end in September 2015. This supplement to Academic Pediatrics is intended to inform discussions about CHIP's future. Most of the new research presented comes from a large evaluation of CHIP mandated by Congress in the CHIPRA. Since CHIP started in 1997, millions of lower-income children have secured health insurance coverage and needed care, reducing the financial burdens and stress on their families. States made substantial progress in simplifying enrollment and retention. When implemented optimally, Express Lane Eligibility has the potential to help cover more of the millions of eligible children who remain uninsured. Children move frequently between Medicaid and CHIP, and many experienced a gap in coverage with this transition. CHIP enrollees had good access to care. For nearly every health care access, use, care, and cost measure examined, CHIP enrollees fared better than uninsured children. Access in CHIP was similar to private coverage for most measures, but financial burdens were substantially lower and access to weekend and nighttime care was not as good. The Affordable Care Act coverage options have the potential to reduce uninsured rates among children, but complex transition issues must first be resolved to ensure families have access to affordable coverage, leading many stakeholders to recommend funding for CHIP be continued. Copyright © 2015 Academic Pediatric Association. All rights reserved.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice

PubMed Central

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-01-01

Abstract Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective. PMID:29471332

Front-End Processing of Cell Lysates for Enhanced Chip-Based Detection

DTIC Science & Technology

2006-07-28

manipulation used in lab-on-a-chip devices. A small unknown sample is first mixed with the PNA surfactants (“PNAA”) to tag the DNA targets, and then the...unknown sample is first mixed with the PNA surfactants (hereafter referred to as “PNA amphiphiles” or “PNAA”) to tag the DNA targets, and then the...prolate ellipsoid, and mixed PNAA/SDS micelles form spherical micelles. On addition of complementary DNA, the PNAA/DNA duplexes do not participate in

A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends

PubMed Central

Kern, David M.; Nicholls, Peter K.; Page, David C.

2016-01-01

The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used for the previous studies in mitotic cells and a novel, shorter mitotic isoform. Unlike the long isoform, short SKAP rescues SKAP depletion in mitosis and displays robust microtubule plus-end tracking, including localization to astral microtubules. Eliminating SKAP microtubule binding results in severe chromosome segregation defects. In contrast, SKAP mutants specifically defective for plus-end tracking facilitate proper chromosome segregation but display spindle positioning defects. Cells lacking SKAP plus-end tracking have reduced Clasp1 localization at microtubule plus ends and display increased lateral microtubule contacts with the cell cortex, which we propose results in unbalanced dynein-dependent cortical pulling forces. Our work reveals an unappreciated role for the Astrin/SKAP complex as an astral microtubule mediator of mitotic spindle positioning. PMID:27138257

Alteration of the end-plane angle in press-fit cylindrical stem radial head prosthesis: an in vitro study.

PubMed

Luenam, Suriya; Chalongviriyalert, Piti; Kosiyatrakul, Arkaphat; Thanawattano, Chusak

2012-01-01

Many studies comparing the morphology of native radial head with the prosthesis have been published. However, there is limited information regarding the postoperative alignment of the articular surface following the radial head replacement. The purpose of this study is to evaluate the alteration of the end-plane angle in the modular radial head prosthesis with a press-fit cementless cylindrical stem. The study used 36 cadaveric radii. The press-fit size prosthesis with cylindrical stem was inserted into each specimen. The end-plane angles of the radial head before and after prosthetic replacement, were measured in coronal and sagittal planes with a digital inclinometer. The data were analyzed by paired t-test. From paired t-test, there were statistically symmetrical end-plane angles before and after radial head replacement in both coronal and sagittal planes (p-value < 0.01). The mean of radial head end-plane angle alteration in the coronal plane was 3.62° (SD, 2.76°) (range, 0.3°-8.9°). In the sagittal plane, the mean of alteration was 5.85° (SD, 3.56°) degrees (range, 0.3° - 14.2°). The modular radial head prosthesis with cylindrical stem is in vitro able to restore the native end-plane angles of radial heads statistically when used in a press-fit fashion.

mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

PubMed Central

Hämäläinen, Riikka H.; Ahlqvist, Kati J.; Ellonen, Pekka; Lepistö, Maija; Logan, Angela; Otonkoski, Timo; Murphy, Michael P.; Suomalainen, Anu

2015-01-01

Summary mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal. Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function. PMID:26027936

Adipose‑derived stem cells and hyaluronic acid based gel compatibility, studied in vitro.

PubMed

Guo, Jiayan; Guo, Shu; Wang, Yuxin; Yu, Yanqiu

2017-10-01

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro.

Holographic pixel super-resolution in portable lensless on-chip microscopy using a fiber-optic array.

PubMed

Bishara, Waheb; Sikora, Uzair; Mudanyali, Onur; Su, Ting-Wei; Yaglidere, Oguzhan; Luckhart, Shirley; Ozcan, Aydogan

2011-04-07

We report a portable lensless on-chip microscope that can achieve <1 µm resolution over a wide field-of-view of ∼ 24 mm(2) without the use of any mechanical scanning. This compact on-chip microscope weighs ∼ 95 g and is based on partially coherent digital in-line holography. Multiple fiber-optic waveguides are butt-coupled to light emitting diodes, which are controlled by a low-cost micro-controller to sequentially illuminate the sample. The resulting lensfree holograms are then captured by a digital sensor-array and are rapidly processed using a pixel super-resolution algorithm to generate much higher resolution holographic images (both phase and amplitude) of the objects. This wide-field and high-resolution on-chip microscope, being compact and light-weight, would be important for global health problems such as diagnosis of infectious diseases in remote locations. Toward this end, we validate the performance of this field-portable microscope by imaging human malaria parasites (Plasmodium falciparum) in thin blood smears. Our results constitute the first-time that a lensfree on-chip microscope has successfully imaged malaria parasites.

Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: implications for stem cell mitosis and centrosome dynamics.

PubMed

Mannino, Mariella; Gomez-Roman, Natividad; Hochegger, Helfrid; Chalmers, Anthony J

2014-07-01

Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

7 CFR 52.780 - Defects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PROCESSED FRUITS AND VEGETABLES, PROCESSED PRODUCTS THEREOF, AND CERTAIN OTHER PROCESSED FOOD PRODUCTS 1... means any vegetable substance (including, but not being limited to, a leaf or a stem, and any portions...

Drivers Motivating Community Health Improvement Plan Completion by Local Public Health Agencies and Community Partners in the Rocky Mountain Region and Western Plains.

PubMed

Hill, Anne; Wolf, Holly J; Scallan, Elaine; Case, Jenny; Kellar-Guenther, Yvonne

There are numerous drivers that motivate completion of community health improvement plans (CHIPs). Some are more obvious and include voluntary public health accreditation, state requirements, federal and state funding, and nonprofit hospital requirements through IRS regulations. Less is known about other drivers, including involvement of diverse partners and belief in best practices, that may motivate CHIP completion. This research investigated the drivers that motivated CHIP completion based on experiences of 51 local public health agencies (LPHAs). An explanatory mixed-methods design, including closed- and open-ended survey questions and key informant interviews, was used to understand the drivers that motivated CHIP completion. Analysis of survey data involved descriptive statistics. Classical content analysis was used for qualitative data to clarify survey findings. The surveys and key informant interviews were conducted in the Rocky Mountain Region and Western Plains among 51 medium and large LPHAs in Colorado, Kansas, Montana, Nebraska, North Dakota, South Dakota, Utah, and Wyoming. More than 50% of respondents were public health directors; the balance of the respondents were division/program directors, accreditation coordinators, and public health planners. CHIP completion. Most LPHAs in the Rocky Mountains and Western Plains have embraced developing and publishing a CHIP, with 80% having completed their plan and another 13% working on it. CHIP completion is motivated by a belief in best practices, with LPHAs and partners seeing the benefit of quality improvement activities linked to the CHIP and the investment of nonprofit hospitals in the process. Completing a CHIP is strengthened through engagement of diverse partners and a well-functioning partnership. The future of CHIP creation depends on LPHAs and partners investing in the CHIP as a best practice, dedicating personnel to CHIP activities, and enhancing leadership skills to contribute to a synergistic partnership by effectively working and communicating with diverse partners and developing and achieving common goals.

Epigenetically Modified Bone Marrow Stromal Cells in Silk Scaffolds Promote Craniofacial Bone Repair and Wound Healing.

PubMed

Han, Qianqian; Yang, Pishan; Wu, Yuwei; Meng, Shu; Sui, Lei; Zhang, Lan; Yu, Liming; Tang, Yin; Jiang, Hua; Xuan, Dongying; Kaplan, David L; Kim, Sung Hoon; Tu, Qisheng; Chen, Jake

2015-08-01

Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in craniofacial and bone development. In this study, we hypothesize that PHF8 promotes osteoblastogenesis by epigenetically regulating the expression of a nuclear matrix protein, special AT-rich sequence-binding protein 2 (SATB2) that plays pivotal roles in skeletal patterning and osteoblast differentiation. Our results showed that expression levels of PHF8 and SATB2 in preosteoblasts and bone marrow stromal cells (BMSCs) increased simultaneously during osteogenic induction. Overexpressing PHF8 in these cells upregulated the expression of SATB2, Runx2, osterix, and bone matrix proteins. Conversely, knockdown of PHF8 reduced the expression of these genes. Furthermore, ChIP assays confirmed that PHF8 specifically bound to the transcription start site (TSS) of the SATB2 promoter, and the expression of H3K9me1 at the TSS region of SATB2 decreased in PHF8 overexpressed group. Implantation of the BMSCs overexpressing PHF8 with silk protein scaffolds promoted bone regeneration in critical-sized defects in mouse calvaria. Taken together, our results demonstrated that PHF8 epigenetically modulates SATB2 activity, triggering BMSCs osteogenic differentiation and facilitating bone formation and regeneration in biodegradable silk scaffolds.

Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

PubMed

Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

2018-07-01

Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

FANCL ubiquitinates β-catenin and enhances its nuclear function

PubMed Central

Rotelli, Michael D.; Petersen, Curtis L.; Kaech, Stefanie; Nelson, Whitney D.; Yates, Jane E.; Hanlon Newell, Amy E.; Olson, Susan B.; Druker, Brian J.; Bagby, Grover C.

2012-01-01

Bone marrow failure is a nearly universal complication of Fanconi anemia. The proteins encoded by FANC genes are involved in DNA damage responses through the formation of a multisubunit nuclear complex that facilitates the E3 ubiquitin ligase activity of FANCL. However, it is not known whether loss of E3 ubiquitin ligase activity accounts for the hematopoietic stem cell defects characteristic of Fanconi anemia. Here we provide evidence that FANCL increases the activity and expression of β-catenin, a key pluripotency factor in hematopoietic stem cells. We show that FANCL ubiquitinates β-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions. Specifically, β-catenin modified with lysine-11 ubiquitin chain extension efficiently activates a lymphocyte enhancer-binding factor-T cell factor reporter. We also show that FANCL-deficient cells display diminished capacity to activate β-catenin leading to reduced transcription of Wnt-responsive targets c-Myc and Cyclin D1. Suppression of FANCL expression in normal human CD34+ stem and progenitor cells results in fewer β-catenin active cells and inhibits expansion of multilineage progenitors. Together, these results suggest that diminished Wnt/β-catenin signaling may be an underlying molecular defect in FANCL-deficient hematopoietic stem cells leading to their accelerated loss. PMID:22653977

Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension

PubMed Central

de Oliveira, Lucas Felipe; Almeida, Thalles Ramos; Ribeiro Machado, Marcus Paulo; Cuba, Marilia Beatriz; Alves, Angélica Cristina; da Silva, Marcos Vinícius; Rodrigues Júnior, Virmondes; Dias da Silva, Valdo José

2015-01-01

Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH. PMID:26300922

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE PAGES

Qian, Fang; Huang, Chao; Lin, Yi-Dong; ...

2017-04-18

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Fang; Huang, Chao; Lin, Yi-Dong

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Composition of Mineral Produced by Dental Mesenchymal Stem Cells

PubMed Central

Volponi, A.A.; Gentleman, E.; Fatscher, R.; Pang, Y.W.Y.; Gentleman, M.M.; Sharpe, P.T.

2015-01-01

Mesenchymal stem cells isolated from different dental tissues have been described to have osteogenic/odontogenic-like differentiation capacity, but little attention has been paid to the biochemical composition of the material that each produces. Here, we used Raman spectroscopy to analyze the mineralized materials produced in vitro by different dental cell populations, and we compared them with the biochemical composition of native dental tissues. We show that different dental stem cell populations produce materials that differ in their mineral and matrix composition and that these differ from those of native dental tissues. In vitro, BCMP (bone chip mass population), SCAP (stem cells from apical papilla), and SHED (stem cells from human-exfoliated deciduous teeth) cells produce a more highly mineralized matrix when compared with that produced by PDL (periodontal ligament), DPA (dental pulp adult), and GF (gingival fibroblast) cells. Principal component analyses of Raman spectra further demonstrated that the crystallinity and carbonate substitution environments in the material produced by each cell type varied, with DPA cells, for example, producing a more carbonate-substituted mineral and with SCAP, SHED, and GF cells creating a less crystalline material when compared with other dental stem cells and native tissues. These variations in mineral composition reveal intrinsic differences in the various cell populations, which may in turn affect their specific clinical applications. PMID:26253190

Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss

PubMed Central

Harris, Stephen E; Rediske, Michael; Neitzke, Rebecca; Rakian, Audrey

2017-01-01

The periodontium is a complex tissue with epithelial components and a complex set of mesodermal derived alveolar bone, cellular and a cellular cementum, and tendon like ligaments (PDL). The current evidence demonstrates that the major pool of periodontal stem cells is derived from a population of micro vascular associated aSMA-positive stem/progenitor (PSC) cells that by lineage tracing form all three major mesodermal derived components of the periodontium. With in vitro aSMA+ stem cells, transcriptome and chip- seq experiments, the gene network and enhancer maps were determined at several differentiation states of the PSC. Current work on the role of the Bmp2 gene in the periodontal stem cell differentiation demonstrated that this Wnt regulated gene, Bmp2, is necessary for differentiation to all three major mesodermal derived component of the periodontium. The mechanism and use of Sclerostin antibody as an activator of Wnt signaling and Bmp2 gene as a potential route to treat craniofacial bone loss is discussed. As well, the mechanism and use of Pth in the treatment of periodontal bone loss or other craniofacial bone loss is presented in this review. PMID:29457146

Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.

PubMed

Ming, Li; Zhipeng, Yuan; Fei, Yu; Feng, Rao; Jian, Weng; Baoguo, Jiang; Yongqiang, Wen; Peixun, Zhang

2018-03-26

Cartilage defect is common in clinical but notoriously difficult to treat for low regenerative and migratory capacity of chondrocytes. Biodegradable tissue engineering nano-scaffold with a lot of advantages has been the direction of material to repair cartilage defect in recent years. The objective of our study is to establish a biodegradable drug-loading synthetic polymer (PLA) and biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of cartilage defect. We designed a microfluidic chip-based drug-screening device to select the optimum concentration of resveratrol, which has strong protective capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a result, we successfully cultured primary chondrocytes and screened the appropriate concentrations of resveratrol by the microfluidic device. We also smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano-scaffolds and compared the properties and therapeutic effects of cartilage defect in rats. In summary, our microfluidic device is a simple but efficient platform for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could greatly promote the cartilage formation. It would be possible for materials and medical researchers to explore individualized pharmacotherapy and drug-loading synthetic polymer and biopolymer composite tissue engineering scaffolds for the repair of cartilage defect in future.

A three-dimensional optimal sawing system for small sawmills in central Appalachia

Treesearch

Wenshu Lin; Jingxin Wang; R. Edward. Thomas

2011-01-01

A three-dimensional (3D) log sawing optimization system was developed to perform 3D log generation, opening face determination, sawing simulation, and lumber grading. Superficial characteristics of logs such as length, large-end and small-end diameters, and external defects were collected from local sawmills. Internal log defect positions and shapes were predicted...

7 CFR 52.3188 - Work sheet for dried prunes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... maximum Total of all defects, including off-color 10 percent 15 percent No limit except as indicated below. Total of all defects, including off-color and poor texture 20 percent Poor texture, end cracks, skin or... material, insect infestation, decay But no more than 6 percent But no more than 8 percent End cracks,2 skin...

7 CFR 52.3188 - Work sheet for dried prunes.

Code of Federal Regulations, 2012 CFR

2012-01-01

... defects, including off-color 10 percent 15 percent No limit except as indicated below. Total of all defects, including off-color and poor texture 20 percent Poor texture, end cracks, skin or flesh damage, 3..., decay But no more than 6 percent But no more than 8 percent End cracks,2 skin or flesh damage, 3...

7 CFR 52.3188 - Work sheet for dried prunes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... maximum Total of all defects, including off-color 10 percent 15 percent No limit except as indicated below. Total of all defects, including off-color and poor texture 20 percent Poor texture, end cracks, skin or... material, insect infestation, decay But no more than 6 percent But no more than 8 percent End cracks,2 skin...

Theoretical investigation on nanoparticle concentrations in optoelectrofluidic chip based on diffusion, convection, and migration

NASA Astrophysics Data System (ADS)

Hu, Sheng; Lv, Jiangtao; Si, Guangyuan

2016-10-01

A numerical model and simulation relative to an optoelectrofluidic chip has been presented in this article. Both dielectrophoretic and electroosmotic force attracting the nano-sized particles could be studied by the diffusion, convection, and migration equations. For the nano-sized particles, the protein with radius 3.6 nm is considered as the objective particle. The electroosmosis dependent upon applied frequency is calculated, which range 102 Hz from 108 Hz, and provides the much stronger force to enrich proteins than dielectrophoresis (DEP). Meanwhile, the induced light pattern size significantly affecting the concentration distribution is simulated. In this end, the concentration curve has verified that the optoelectrofluidic chip can be capable of manipulating and assembling the suspended submicron particles.

Towards a Chemiresistive Sensor-Integrated Electronic Nose: A Review

PubMed Central

Chiu, Shih-Wen; Tang, Kea-Tiong

2013-01-01

Electronic noses have potential applications in daily life, but are restricted by their bulky size and high price. This review focuses on the use of chemiresistive gas sensors, metal-oxide semiconductor gas sensors and conductive polymer gas sensors in an electronic nose for system integration to reduce size and cost. The review covers the system design considerations and the complementary metal-oxide-semiconductor integrated technology for a chemiresistive gas sensor electronic nose, including the integrated sensor array, its readout interface, and pattern recognition hardware. In addition, the state-of-the-art technology integrated in the electronic nose is also presented, such as the sensing front-end chip, electronic nose signal processing chip, and the electronic nose system-on-chip. PMID:24152879

On-chip copper-dielectric interference filters for manufacturing of ambient light and proximity CMOS sensors.

PubMed

Frey, Laurent; Masarotto, Lilian; D'Aillon, Patrick Gros; Pellé, Catherine; Armand, Marilyn; Marty, Michel; Jamin-Mornet, Clémence; Lhostis, Sandrine; Le Briz, Olivier

2014-07-10

Filter technologies implemented on CMOS image sensors for spectrally selective applications often use a combination of on-chip organic resists and an external substrate with multilayer dielectric coatings. The photopic-like and near-infrared bandpass filtering functions respectively required by ambient light sensing and user proximity detection through time-of-flight can be fully integrated on chip with multilayer metal-dielectric filters. Copper, silicon nitride, and silicon oxide are the materials selected for a technological proof-of-concept on functional wafers, due to their immediate availability in front-end semiconductor fabs. Filter optical designs are optimized with respect to specific performance criteria, and the robustness of the designs regarding process errors are evaluated for industrialization purposes.

First results of the front-end ASIC for the strip detector of the PANDA MVD

NASA Astrophysics Data System (ADS)

Quagli, T.; Brinkmann, K.-T.; Calvo, D.; Di Pietro, V.; Lai, A.; Riccardi, A.; Ritman, J.; Rivetti, A.; Rolo, M. D.; Stockmanns, T.; Wheadon, R.; Zambanini, A.

2017-03-01

PANDA is a key experiment of the future FAIR facility and the Micro Vertex Detector (MVD) is the innermost part of its tracking system. PASTA (PAnda STrip ASIC) is the readout chip for the strip part of the MVD. The chip is designed to provide high resolution timestamp and charge information with the Time over Threshold (ToT) technique. Its architecture is based on Time to Digital Converters with analog interpolators, with a time bin width of 50 ps. The chip implements Single Event Upset (SEU) protection techniques for its digital parts. A first full-size prototype with 64 channels was produced in a commercial 110 nm CMOS technology and the first characterizations of the prototype were performed.

Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow

PubMed Central

Kim, Su-Hwan; Kim, Young-Sung; Lee, Su-Yeon; Kim, Kyoung-Hwa; Lee, Yong-Moo; Kim, Won-Kyung

2011-01-01

Purpose The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions This study demonstrated the genome-wide gene expression patterns of STRO-1+ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells. PMID:21954424

Fabric defect detection based on faster R-CNN

NASA Astrophysics Data System (ADS)

Liu, Zhoufeng; Liu, Xianghui; Li, Chunlei; Li, Bicao; Wang, Baorui

2018-04-01

In order to effectively detect the defects for fabric image with complex texture, this paper proposed a novel detection algorithm based on an end-to-end convolutional neural network. First, the proposal regions are generated by RPN (regional proposal Network). Then, Fast Region-based Convolutional Network method (Fast R-CNN) is adopted to determine whether the proposal regions extracted by RPN is a defect or not. Finally, Soft-NMS (non-maximum suppression) and data augmentation strategies are utilized to improve the detection precision. Experimental results demonstrate that the proposed method can locate the fabric defect region with higher accuracy compared with the state-of- art, and has better adaptability to all kinds of the fabric image.

A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis VII

PubMed Central

Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes

2012-01-01

Hundreds of different human skeletal disorders have been characterized at molecular level and a growing number of resembling dysplasias with orthologous genetic defects are being reported in dogs. This study describes a novel genetic defect in the Brazilian Terrier breed causing a congenital skeletal dysplasia. Affected puppies presented severe skeletal deformities observable within the first month of life. Clinical characterization using radiographic and histological methods identified delayed ossification and spondyloepiphyseal dysplasia. Pedigree analysis suggested an autosomal recessive disorder, and we performed a genome-wide association study to map the disease locus using Illumina’s 22K SNP chip arrays in seven cases and eleven controls. A single association was observed near the centromeric end of chromosome 6 with a genome-wide significance after permutation (pgenome  = 0.033). The affected dogs shared a 13-Mb homozygous region including over 200 genes. A targeted next-generation sequencing of the entire locus revealed a fully segregating missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB). The mutation was confirmed in a population of 202 Brazilian terriers (p = 7,71×10−29). GUSB defects cause mucopolysaccharidosis VII (MPS VII) in several species and define the skeletal syndrome in Brazilian Terriers. Our results provide new information about the correlation of the GUSB genotype to phenotype and establish a novel canine model for MPS VII. Currently, MPS VII lacks an efficient treatment and this model could be utilized for the development and validation of therapeutic methods for better treatment of MPS VII patients. Finally, since almost one third of the Brazilian terrier population carries the mutation, breeders will benefit from a genetic test to eradicate the detrimental disease from the breed. PMID:22815736

Characterization of emission microscopy and liquid crystal thermography in IC fault localization

NASA Astrophysics Data System (ADS)

Lau, C. K.; Sim, K. S.

2013-05-01

This paper characterizes two fault localization techniques - Emission Microscopy (EMMI) and Liquid Crystal Thermography (LCT) by using integrated circuit (IC) leakage failures. The majority of today's semiconductor failures do not reveal a clear visual defect on the die surface and therefore require fault localization tools to identify the fault location. Among the various fault localization tools, liquid crystal thermography and frontside emission microscopy are commonly used in most semiconductor failure analysis laboratories. Many people misunderstand that both techniques are the same and both are detecting hot spot in chip failing with short or leakage. As a result, analysts tend to use only LCT since this technique involves very simple test setup compared to EMMI. The omission of EMMI as the alternative technique in fault localization always leads to incomplete analysis when LCT fails to localize any hot spot on a failing chip. Therefore, this research was established to characterize and compare both the techniques in terms of their sensitivity in detecting the fault location in common semiconductor failures. A new method was also proposed as an alternative technique i.e. the backside LCT technique. The research observed that both techniques have successfully detected the defect locations resulted from the leakage failures. LCT wass observed more sensitive than EMMI in the frontside analysis approach. On the other hand, EMMI performed better in the backside analysis approach. LCT was more sensitive in localizing ESD defect location and EMMI was more sensitive in detecting non ESD defect location. Backside LCT was proven to work as effectively as the frontside LCT and was ready to serve as an alternative technique to the backside EMMI. The research confirmed that LCT detects heat generation and EMMI detects photon emission (recombination radiation). The analysis results also suggested that both techniques complementing each other in the IC fault localization. It is necessary for a failure analyst to use both techniques when one of the techniques produces no result.

Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization

PubMed Central

2009-01-01

Background Array genomic hybridization is being used clinically to detect pathogenic copy number variants in children with intellectual disability and other birth defects. However, there is no agreement regarding the kind of array, the distribution of probes across the genome, or the resolution that is most appropriate for clinical use. Results We performed 500 K Affymetrix GeneChip® array genomic hybridization in 100 idiopathic intellectual disability trios, each comprised of a child with intellectual disability of unknown cause and both unaffected parents. We found pathogenic genomic imbalance in 16 of these 100 individuals with idiopathic intellectual disability. In comparison, we had found pathogenic genomic imbalance in 11 of 100 children with idiopathic intellectual disability in a previous cohort who had been studied by 100 K GeneChip® array genomic hybridization. Among 54 intellectual disability trios selected from the previous cohort who were re-tested with 500 K GeneChip® array genomic hybridization, we identified all 10 previously-detected pathogenic genomic alterations and at least one additional pathogenic copy number variant that had not been detected with 100 K GeneChip® array genomic hybridization. Many benign copy number variants, including one that was de novo, were also detected with 500 K array genomic hybridization, but it was possible to distinguish the benign and pathogenic copy number variants with confidence in all but 3 (1.9%) of the 154 intellectual disability trios studied. Conclusion Affymetrix GeneChip® 500 K array genomic hybridization detected pathogenic genomic imbalance in 10 of 10 patients with idiopathic developmental disability in whom 100 K GeneChip® array genomic hybridization had found genomic imbalance, 1 of 44 patients in whom 100 K GeneChip® array genomic hybridization had found no abnormality, and 16 of 100 patients who had not previously been tested. Effective clinical interpretation of these studies requires considerable skill and experience. PMID:19917086

Microfluidic systems for stem cell-based neural tissue engineering.

PubMed

Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

The perceptions of pre-service and in-service teachers regarding a project-based STEM approach to teaching science.

PubMed

Siew, Nyet Moi; Amir, Nazir; Chong, Chin Lu

2015-01-01

Whilst much attention has focused on project-based approaches to teaching Science, Technology, Engineering and Mathematics (STEM) subjects, little has been reported on the views of South-East Asian science teachers on project-based STEM approaches. Such knowledge could provide relevant information for education training institutions on how to influence innovative teaching of STEM subjects in schools. This article reports on a study that investigated the perceptions of 25 pre-service and 21 in-service Malaysian science teachers in adopting an interdisciplinary project-based STEM approach to teaching science. The teachers undertook an eight hour workshop which exposed them to different science-based STEM projects suitable for presenting science content in the Malaysian high school science syllabus. Data on teachers' perceptions were captured through surveys, interviews, open-ended questions and classroom discussion before and at the end of the workshop. Study findings showed that STEM professional development workshops can provide insights into the support required for teachers to adopt innovative, effective, project-based STEM approaches to teaching science in their schools.

Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia.

PubMed

Onorati, Marco; Li, Zhen; Liu, Fuchen; Sousa, André M M; Nakagawa, Naoki; Li, Mingfeng; Dell'Anno, Maria Teresa; Gulden, Forrest O; Pochareddy, Sirisha; Tebbenkamp, Andrew T N; Han, Wenqi; Pletikos, Mihovil; Gao, Tianliuyun; Zhu, Ying; Bichsel, Candace; Varela, Luis; Szigeti-Buck, Klara; Lisgo, Steven; Zhang, Yalan; Testen, Anze; Gao, Xiao-Bing; Mlakar, Jernej; Popovic, Mara; Flamand, Marie; Strittmatter, Stephen M; Kaczmarek, Leonard K; Anton, E S; Horvath, Tamas L; Lindenbach, Brett D; Sestan, Nenad

2016-09-06

The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs) to Identify Osteoclast Defects in Rare Genetic Bone Disorders

PubMed Central

Chen, I-Ping

2014-01-01

More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs) can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts. PMID:25621177

PRMT7 Preserves Satellite Cell Regenerative Capacity.

PubMed

Blanc, Roméo Sébastien; Vogel, Gillian; Chen, Taiping; Crist, Colin; Richard, Stéphane

2016-02-16

Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7(-/-) adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Optimization of a polydopamine (PD)-based coating method and polydimethylsiloxane (PDMS) substrates for improved mouse embryonic stem cell (ESC) pluripotency maintenance and cardiac differentiation.

PubMed

Fu, Jiayin; Chuah, Yon Jin; Ang, Wee Tong; Zheng, Nan; Wang, Dong-An

2017-05-30

Myocardiocyte derived from pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), is a promising cell source for cardiac tissue engineering. Combined with microfluidic technologies, a heart-on-a-chip is very likely to be developed and function as a platform for high throughput drug screening. Polydimethylsiloxane (PDMS) silicone elastomer is a widely-used biomaterial for the investigation of cell-substrate interactions and biochip fabrication. However, the intrinsic PDMS surface hydrophobicity inhibits cell adhesion on the PDMS surface, and PDMS surface modification is required for effective cell adhesion. Meanwhile, the formulation of PDMS also affects the behaviors of the cells. To fabricate PDMS-based biochips for ESC pluripotency maintenance and cardiac differentiation, PDMS surface modification and formulation were optimized in this study. We found that a polydopamine (PD) with gelatin coating greatly improved the ESC adhesion, proliferation and cardiac differentiation on its surface. In addition, different PDMS substrates varied in their surface properties, which had different impacts on ESCs, with the 40 : 1 PDMS substrate being more favorable for ESC adhesion and proliferation as well as embryoid body (EB) attachment than the other PDMS substrates. Moreover, the ESC pluripotency was best maintained on the 5 : 1 PDMS substrate, while the cardiac differentiation of the ESCs was optimal on the 40 : 1 PDMS substrate. Based on the optimized coating method and PDMS formulation, biochips with two different designs were fabricated and evaluated. Compared to the single channels, the multiple channels on the biochips could provide larger areas and accommodate more nutrients to support improved ESC pluripotency maintenance and cardiac differentiation. These results may contribute to the development of a real heart-on-a-chip for high-throughput drug screening in the future.

Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

PubMed

Hoefer, J; Streif, W; Kilo, J; Grimm, M; Berger, G; Velik-Salchner, C

2012-10-01

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved. © Georg Thieme Verlag KG Stuttgart · New York.

Yield and Nutrient Removal by Whole-Tree Harvest of a Young Bottomland Hardwood Stand

Treesearch

John K. Francis

1984-01-01

The yield and nutrient withdrawal by whole-tree harvest of young bottomland hardwoods has heretofore been unknown. In this study of intensive harvest, samples of chipped whole trees and soil from 16 test plots were analyzed for nutrient content. Eighty-two percent of the stems and 59 percent of the dry weight were green ash. The balance was divided among a number of...

Lithographic microfabrication of biocompatible polymers for tissue engineering and lab-on-a-chip applications

NASA Astrophysics Data System (ADS)

Balciunas, Evaldas; Jonusauskas, Linas; Valuckas, Vytautas; Baltriukiene, Daiva; Bukelskiene, Virginija; Gadonas, Roaldas; Malinauskas, Mangirdas

2012-06-01

In this work, a combination of Direct Laser Writing (DLW), PoliDiMethylSiloxane (PDMS) soft lithography and UV lithography was used to create cm- scale microstructured polymer scaolds for cell culture experiments out of dierent biocompatible materials: novel hybrid organic-inorganic SZ2080, PDMS elastomer, biodegradable PEG- DA-258 and SU-8. Rabbit muscle-derived stem cells were seeded on the fabricated dierent periodicity scaolds to evaluate if the relief surface had any eect on cell proliferation. An array of microlenses was fabricated using DLW out of SZ2080 and replicated in PDMS and PEG-DA-258, showing good potential applicability of the used techniques in many other elds like micro- and nano- uidics, photonics, and MicroElectroMechanical Systems (MEMS). The synergetic employment of three dierent fabrication techniques allowed to produce desired objects with low cost, high throughput and precision as well as use materials that are dicult to process by other means (PDMS and PEG-DA-258). DLW is a relatively slow fabrication method, since the object has to be written point-by-point. By applying PDMS soft lithography, we were enabled to replicate laser-fabricated scaolds for stem cell growth and micro-optical elements for lab-on-a-chip applications with high speed, low cost and good reproducible quality.

A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

PubMed Central

Randolph, Matthew E.; Pavlath, Grace K.

2015-01-01

The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

STEM-HAADF electron microscopy analysis of the central dark line defect of human tooth enamel crystallites.

PubMed

Gasga, Jose Reyes; Carbajal-de-la-Torre, Georgina; Bres, Etienne; Gil-Chavarria, Ivet M; Rodríguez-Hernández, Ana G; Garcia-Garcia, Ramiro

2008-02-01

When human tooth enamel is observed with the Transmission Electron Microscope (TEM), a structural defect is registered in the central region of their nanometric grains or crystallites. This defect has been named as Central Dark Line (CDL) and its structure and function in the enamel structure have been unknown yet. In this work we present the TEM analysis to these crystallites using the High Angle Annular Dark Field (HAADF) technique. Our results suggest that the CDL region is the calcium richest part of the human tooth enamel crystallites.

Mutations in yeast proliferating cell nuclear antigen define distinct sites for interaction with DNA polymerase delta and DNA polymerase epsilon.

PubMed Central

Eissenberg, J C; Ayyagari, R; Gomes, X V; Burgers, P M

1997-01-01

The importance of the interdomain connector loop and of the carboxy-terminal domain of Saccharomyces cerevisiae proliferating cell nuclear antigen (PCNA) for functional interaction with DNA polymerases delta (Poldelta) and epsilon (Pol epsilon) was investigated by site-directed mutagenesis. Two alleles, pol30-79 (IL126,128AA) in the interdomain connector loop and pol30-90 (PK252,253AA) near the carboxy terminus, caused growth defects and elevated sensitivity to DNA-damaging agents. These two mutants also had elevated rates of spontaneous mutations. The mutator phenotype of pol30-90 was due to partially defective mismatch repair in the mutant. In vitro, the mutant PCNAs showed defects in DNA synthesis. Interestingly, the pol30-79 mutant PCNA (pcna-79) was most defective in replication with Poldelta, whereas pcna-90 was defective in replication with Pol epsilon. Protein-protein interaction studies showed that pcna-79 and pcna-90 failed to interact with Pol delta and Pol epsilon, respectively. In addition, pcna-90 was defective in interaction with the FEN-1 endo-exonuclease (RTH1 product). A loss of interaction between pcna-79 and the smallest subunit of Poldelta, the POL32 gene product, implicates this interaction in the observed defect with the polymerase. Neither PCNA mutant showed a defect in the interaction with replication factor C or in loading by this complex. Processivity of DNA synthesis by the mutant holoenzyme containing pcna-79 was unaffected on poly(dA) x oligo(dT) but was dramatically reduced on a natural template with secondary structure. A stem-loop structure with a 20-bp stem formed a virtually complete block for the holoenzyme containing pcna-79 but posed only a minor pause site for wild-type holoenzyme, indicating a function of the POL32 gene product in allowing replication past structural blocks. PMID:9343398