bluuebunny/crossref_metadata_2025 huggingface dataset:
Autotransplantation of Unmanipulated Bone Marrow into Scarred Myocardium is Safe and Enhances Cardiac Function in Humans
Authors: Galiñanes Manuel , Loubani Mahmoud , Davies Joan , Chin Derek , Pasi John , Bell Peter R.
Published: September 2014

Stem cell transplants into damaged myocardium may have the potential to improve cardiac function. We investigated the safety of transplanting unmanipulated autologous bone marrow into infarcted myocardium of patients undergoing coronary bypass surgery and assessed its efficacy to improve cardiac function. Fourteen patients with one or more areas of transmural myocardial infarction were studied. Autologous bone marrow was obtained by sternal bone aspirate at the time of surgery, diluted in autologous serum at a ratio of 1:2, and then injected 1 cm apart into the mid-depth of the left ventricular scar. There were no deaths, no perioperative myocardial infarctions, and no significant ventricular arrhythmias. Dobutamine stress echocardiography demonstrated overall improvement in the global and regional left ventricular function 6 weeks and 10 months after surgery. Of 34 infarcted left ventricular segments, 11 were injected with bone marrow alone, 13 were revascularized with a bypass graft alone, and 10 received bone marrow transplantation and a bypass graft in combination. Only the left ventricle segmental wall motion score of the areas injected with bone marrow and receiving a bypass graft in combination improved at low dose and at peak dobutamine stress. These findings suggest that transplantation of unmanipulated autologous bone marrow into scar tissue of the human heart is safe and enhances cardiac function only when used in combination with myocardial revascularization. This benefit can be seen after 6 weeks of the bone marrow transplant and is maintained after 10 months of follow-up.
Transplantation of Adipose Tissue-Derived Stromal Cells Increases Mass and Functional Capacity of Damaged Skeletal Muscle
Authors: Bacou Francis , Andalousi Ramzi Boubaker El , Daussin Paul-André , Micallef Jean-Paul , Levin Jonathan M. , Chammas Michel , Casteilla Louis , Reyne Yves , Nouguès Jean
Published: September 2014

The regenerating skeletal muscle environment is capable of inducing uncommitted progenitors to terminally differentiate. The aim of this work was to determine whether adipose tissue-derived stromal cells were able to participate in muscle regeneration and to characterize the effect on muscle mass and functional capacities after transplantation of these cells. Adipose tissue stromal cells labeled with Adv cyto LacZ from 3-day-old primary cultures (SVF1) were autotransplanted into damaged tibialis anterior muscles. Fifteen days later, β-galactosidase staining of regenerated fibers was detected, showing participation of these cells in muscle regeneration. Two months after SVF1 cell transfer, muscles were heavier, showed a significantly larger fiber section area, and developed a significantly higher maximal force compared with damaged control muscles. These results are similar to those previously obtained after satellite cell transplantation. However, SVF1 transfer also generated a small amount of adipose tissue localized along the needle course. To minimize these adipose contaminants, we transferred cells from 7-day-old secondary cultures of the SVF1, containing only a small proportion of already engaged preadipocytes (SVF2). Under these conditions, no adipose tissue was observed in regenerated muscle but there was also no effect on muscle performances compared with damaged control muscles. This result provides further evidence for the existence of progenitor cells in the stromal fraction of freshly isolated adipose tissue cells, which, under our conditions, keep some of their pluripotent properties in primary cultures.
Long-Term Function of Cryopreserved Rat Hepatocytes in a Coculture System
Authors: Sugimachi Keishi , Sosef Meindert N. , Baust John M. , Fowler Alex , Tompkins Ronald G. , Toner Mehmet
Published: September 2014

The goal of this study was to investigate postpreservation long-term function of cryopreserved primary rat hepatocytes using the hepatocyte/3T3-J2 fibroblast coculture system. The long-term function of thawed hepatocytes cocultured with fibroblasts was evaluated and compared with hepatocytes cultured without fibroblasts. Fresh isolated primary rat hepatocytes were frozen at a controlled rate (−1°C/min) up to −80°C, and then stored in liquid nitrogen for up to 90 days. Thawed hepatocytes were thereafter cocultured with 3T3-J2 murine fibroblasts and cocultivation was monitored for 14 days. The viability of fresh isolated hepatocytes was 91.4%, and that of cryopreserved hepatocytes was 82.1%. Cellular morphology and polarity, which were determined by the localization of actin filaments and connexin-32, were successfully maintained in cryopreserved hepatocytes following cryopreservation. Albumin and urea synthesis reached the maximum level and became stable after day 7 in coculture in both fresh and cryopreserved hepatocytes. Urea synthesis of cryopreserved hepatocytes was maintained 89.0% of nonfrozen fresh control, and albumin production of cryopreserved hepatocytes was 63.7% of control in coculture. Cytochrome P450 activity, which was measured by deethylation of ethoxyresorufin, was also maintained in cryopreserved hepatocytes at 88.6% of nonfrozen fresh control in coculture. The retention of synthetic and detoxification activities was verified to be well preserved during extended low-temperature storage (90 days). Both fresh control and cryopreserved hepatocytes cultured without fibroblast did not retain their synthetic and detoxification functions in long-term culture. These data illustrate that, through the utilization of our cryopreservation procedure, primary hepatocyte function was successfully maintained when placed into coculture configuration following thawing.
Endogenous Pancreatic Enzyme Activity Levels Show no Significant Effect on Human Islet Isolation Yield
Authors: Rose Natisha L. , Palcic Monica M. , Shapiro A. M. James , Lakey Jonathan R. T.
Published: September 2014

Despite advances in human islet isolation, islet yield remains inconsistent and unreliable. In recent studies, it has been suggested that serine proteases, in particular trypsin, have been shown to have a damaging effect on islet yield. This study evaluated enzyme activity levels throughout 42 human islet isolation procedures. Trypsin, chymotrypsin, and elastase activity was determined spectrophotometrically using suitable chromophoric substrates. The results of the islet isolations were rated as successful (n = 19) or unsuccessful (n = 23) based on the islet yield and functionality. The enzyme activity profiles of the isolations were compared. No significant differences in donor-related variables were found in this study. However, in the successful isolations, a significantly greater amount (85.6 ± 1.9%; p = 0.0017) of the pancreas was digested in a significantly shorter digestion time (19.7 ± 0.6 min; p = 0.0054) compared with 74.8 ± 2.5% of digested tissue in 22.6 ± 0.7 min in the poor isolations. This study showed no significant effect of serine protease levels on the outcome of islet isolations, regardless of enzyme inhibitor supplementation. These data suggest that serine protease activity does not sufficiently affect islet yield. However, the data show that the most successful human islet isolations are achieved when the maximum amount of tissue is digested in the shortest amount of time. This suggests that further understanding of the isolation process should focus on the role of the collagenase digestion solution in the dissociation of the endocrine–exocrine tissue connection.
Transient Beneficial Effects of Exendin-4 Treatment on the Function of Microencapsulated Mouse Pancreatic Islets
Authors: Bohman Sara , Waern Ida , Andersson Arne , King Aileen
Published: September 2014

Transplantation of microencapsulated islets may reduce hyperglycemia in the absence of immunosuppression. However, the efficiency of microencapsulated islet transplantation is low, requiring more islets to achieve normoglycemia than in vascularized islet transplantation. Exendin-4 (a glucagon-like receptor agonist) has been previously shown to improve islet transplantation outcome in rodents. We investigated whether this treatment would enhance the function of microencapsulated islets in vitro and in vivo. Encapsulated or naked islets were cultured with or without exendin-4 for 72 h. To test in vitro function, insulin release and glucose oxidation rates were measured in the absence or presence of exendin-4. In addition, in vivo function of a minimal mass of 350 microencapsulated islets was assessed by syngeneic transplantation into the peritoneal cavity of alloxan-diabetic mice. Glucose oxidation rates of microencapsulated islets were improved by 72-h pretreatment with exendin-4. Insulin release was increased both acutely after glucose stimulation and over a 40-h culture period by the presence of exendin-4. Transplantation outcome of microencapsulated islets cultured with exendin-4 was initially improved, but by day 7 there were no differences compared with control cultured microencapsulated islets. Culture of microencapsulated islets with exendin-4 increases glucose oxidation and insulin release rates, but the increased function seen in vitro was not enough to improve the long term outcome in a transplantation model.
The Pivotal Role of RhoA GTPase in the Molecular Signaling of Axon Growth Inhibition after CNS Injury and Targeted Therapeutic Strategies
Authors: Gross Robert E. , Mei Qi , Gutekunst Claire-Anne , Torre Enrique
Published: September 2014

The dogma that the adult central nervous system (CNS) is nonpermissive to axonal regeneration is beginning to fall in the face of increased understanding of the molecular and cellular biology of axon outgrowth. It is now appreciated that axon growth is regulated by a combination of extracellular factors related to the milieu of the developing or adult CNS and the presence of injury, and intracellular factors related to the “growth state” of the developing or regenerating neuron. Several critical points of convergence within the developing or regenerating neuron for mediating intracellular cell signaling effects on the growth cone cytoskeleton have been identified, and their modulation has produced marked increases in axon outgrowth within the “nonpermissive” milieu of the adult injured CNS. One such critical convergence point is the small GTPase RhoA, which integrates signaling events produced by both myelin-associated inhibitors (e.g., NogoA) and astroglial-derived inhibitors (chondroitin sulfate proteoglycans) and regulates the activity of downstream effectors that modulate cytoskeletal dynamics within the growth cone mediating axon outgrowth or retraction. Inhibition of RhoA has been associated with increased outgrowth on nonpermissive substrates in vitro and increased axon regeneration in vivo. We are developing lentiviral vectors that modulate RhoA activity, allowing more long-term expression than is possible with current approaches. These vectors may be useful in regenerative strategies for spinal cord injury, brain injury, and neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, and Huntington's disease.
Engineered Adipose Tissue Formation Enhanced by Basic Fibroblast Growth Factor and a Mechanically Stable Environment
Authors: Cho Seung-Woo , Song Kang Won , Rhie Jong Won , Park Moon Hyang , Choi Cha Yong , Kim Byung-Soo
Published: September 2014

Engineered adipose tissue can be used in plastic and reconstructive surgery to augment soft tissue lost due to mastectomy or lumpectomy. The three-dimensional space provided by a scaffold capable of withstanding in vivo compressive forces and neovascularization may promote engineered adipose tissue formation. The objective of this study was to determine whether voluminous adipose tissue can be engineered by combining a mechanically stable environment with basic fibroblast growth factor (bFGF). Mechanical support structures, fabricated from biodegradable synthetic polymers, were placed into subcutaneous pockets of athymic mice. Human preadipocytes, containing fibrin matrix, with (group 1) or without (group 2) bFGF were injected into the space created by the support structures. Additionally, human preadipocytes containing fibrin matrix, with (group 3) or without (group 4) bFGF, were injected into subcutaneous spaces without support structures. Six weeks after implantation, the original implant volume was approximately maintained in groups 1 and 2, whereas groups 3 and 4 showed significant implant shrinkage. Adipogenesis and angiogenesis were more extensive in the group 1 than any other group. The fraction of human nuclear antigen-positive adipocytes in the implant was highest in group 1. Mouse adipocyte-specific genes were also expressed in the implants, again at the highest levels in group 1. Implanted preadipocyte apoptosis was significantly reduced in the groups treated with bFGF (groups 1 and 3) as opposed to those without (groups 2 and 4). This study demonstrates that combining a mechanically stable environment with bFGF can promote voluminous adipose tissue regeneration. This adipogenesis was likely promoted by the mechanically stable three-dimensional space, enhanced neovascularization, implanted cell survival, and host adipogenic cell migration. The method described in this study could be useful to augment adipose tissue used in plastic and reconstructive surgery.
Comparison of Cell Therapy and Cytokine Therapy for Functional Repair in Ischemic and Nonischemic Heart Failure
Authors: Li Tao-Sheng , Mikamo Akihito , Takahashi Masaya , Suzuki Ryo , Ueda Kazuhiro , Ikeda Yasuhiro , Matsuzaki Masunori , Hamano Kimikazu
Published: September 2014

Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and nonischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and nonischemic heart failure was induced by an IP injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2 × 105 c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p < 0.05 vs. control therapy). In the nonischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p < 0.05 vs. control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of nonischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.
Cell Loss during Pseudoislet Formation Hampers Profound Improvements in Islet Lentiviral Transduction Efficacy for Transplantation Purposes
Authors: Callewaert H. , Gysemans C. , Cardozo A. K. , Elsner M. , Tiedge M. , Eizirik D. L. , Mathieu C.
Published: September 2014

Islet transplantation is a promising treatment in type 1 diabetes, but the need for chronic immunosuppression is a major hurdle to broad applicability. Ex vivo introduction of agents by lentiviral vectors—improving β-cell resistance against immune attack—is an attractive path to pursue. The aim of this study was to investigate whether dissociation of islets to single cells prior to viral infection and reaggregation before transplantation would improve viral transduction efficacy without cytotoxicity. This procedure improved transduction efficacy with a LV-pWPT-CMV-EGFP construct from 11.2 ± 4.1% at MOI 50 in whole islets to 80.0 ± 2.8% at MOI 5. Viability (as measured by Hoechst/PI) and functionality (as measured by glucose challenge) remained high. After transplantation, the transfected pseudoislet aggregates remained EGFP positive for more than 90 days and the expression of EGFP colocalized primarily with the insulin-positive β-cells. No increased vulnerability to immune attack was observed in vitro or in vivo. These data demonstrate that dispersion of islets prior to lentiviral transfection and reaggregation prior to transplantation is a highly efficient way to introduce genes of interest into islets for transplantation purposes in vitro and in vivo, but the amount of β-cells needed for normalization of glycemia was more than eightfold higher when using dispersed cell aggregates versus unmanipulated islets. The high price to pay to reach stable and strong transgene expression in islet cells is certainly an important cell loss.
Chondroitinase ABC Treatment Enhances Synaptogenesis between Transplant and Host Neurons in Model of Retinal Degeneration
Authors: Suzuki Takuya , Akimoto Masayuki , Imai Hiroo , Ueda Yoshiki , Mandai Michiko , Yoshimura Nagahisa , Swaroop Anand , Takahashi Masayo
Published: September 2014

Although recent studies revealed chondroitinase ABC (ChABC), an enzyme that degrades chondroitin sulfate proteoglycans, promotes CNS regeneration in vivo, the usefulness of its application for transplantation is not clear. We investigated if treatment with ChABC can promote synapse formation between graft and host neurons following retinal transplantation. Dissociated retinal cells were prepared from neonatal Nrl-GFP transgenic mice in which rod photoreceptors and their progenitor cells are labeled with GFP. Each cell suspension with or without ChABC (Nrl/ChABC group and Nrl group, respectively) was injected subretinally into the eyes of mice following chemically induced photoreceptor degeneration. The survival and functional integration of the transplanted photoreceptors were examined by histologically and electrophysio-logically. Up to 4 weeks after transplantation, almost all the grafted GFP+ photoreceptor cells were widely distributed at the outer margin of the host retina where the photoreceptor layer was located originally. In the Nrl/ChABC group, 33.6% of the GFP+ photoreceptors elaborated neurites horizontally or vertically, and 4.6% elaborated neurites toward the retina. These neurites extended over the glial seal at the graft–host interface, and established synaptic contacts with neurons in the host retina as determined by confocal microscopy and three-dimensional analysis. Although 30.7% cells (p = 0.68) elaborated neurites in the Nrl group, only 1.2% cells (p < 0.05) projected neurites towards the host tissue and synaptic contacts were rare. Our results illustrate the potential utility of ChABC for enhancing synaptogenesis between transplanted neurons and host retina.
Hepatocyte Transplantation for Glycogen Storage Disease Type Ib
Authors: Lee Kwang-Woong , Lee Ji-Hyun , Shin Sung Wook , Kim Sung Joo , Joh Jae Won , Lee Doo-Hoon , Kim Jong-Won , Park Hwa-Young , Lee Soo-Youn , Lee Hwan Hyo , Park Jin Wan , Kim Shi-Yeon , Yoon Hee-Hoon , Jung Doo-Hee , Choe Yon Ho , Lee Suk-Koo
Published: September 2014

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia, caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib, caused by a deficiency of glucose-6-phosphate transporter (G6PT). We report that a substantial improvement was achieved following several infusions of hepatocytes in a patient with GSD-Ib. Hepatocytes were isolated from the unused cadaveric whole livers of two donors. At the first transplantation, approximately 2 × 109 cells (2% of the estimated recipient's total hepatocytes) were infused. Seven days later 1 × 109 (1% of liver mass) cryopreserved hepatocytes from the same donor were infused, and an additional 3 × 109 (3% of liver mass) cells from the second donor were infused 1 month after the second transplantation. After the hepatocyte transplantation, the patient showed no hypoglycemic symptoms despite the discontinuation of cornstarch meals. Liver biopsies on posttransplantation days 20 and 250 showed a normal level of glucose-6-phosphatase activity in presolubilization assay that was very low before transplantation. This was the first and successful clinical hepatocyte transplantation in Korea. In this study, hepatocyte transplantation allowed a normal diet in a patient with GSD-Ib, with substantial improvement in their quality of life. Hepatocyte transplantation might be an alternative to liver transplantation and dietary therapy in GSD-Ib.
Encapsulation of Porcine Islets Permits Extended Culture Time and Insulin Independence in Spontaneously Diabetic BB Rats
Authors: Gazda Lawrence S. , Vinerean Horatiu V. , Laramore Melissa A. , Diehl Carolyn H. , Hall Richard D. , Rubin Albert L. , Smith Barry H.
Published: September 2014

The ability to culture porcine islets for extended times allows for both their functional assessment and the assurance of their microbiological safety prior to transplantation. We have previously shown that agarose-encapsulated porcine islets can be cultured for at least 24 weeks. In the current study, porcine islet agarose macrobeads cultured for up to 67 weeks were assessed for their ability to restore normoglycemia, respond to an intraperitoneal glucose challenge, maintain spontaneously diabetic BB rats free of insulin therapy for more than 6 months, and for their biocompatibility. Porcine islets were encapsulated in agarose macrobeads and subjected to weekly static perifusion assays for the assessment of insulin production. After in vitro culture for either 9, 40, or 67 weeks, 56–60 macrobeads were transplanted to each spontaneously diabetic BB rat. Transplanted rats were monitored daily for blood glucose levels. Glucose tolerance tests and assessments for porcine C-peptide were conducted at various intervals throughout the study. Normoglycemia (100–200 mg/dl) was initially restored in all islet transplanted rats. Moderate hyperglycemia (200–400 mg/dl) developed at around 30 days posttransplantation and continued throughout the study period of 201–202 days. Importantly, all rats that received encapsulated porcine islets continued to gain weight and were free of exogenous insulin therapy for the entire study. Porcine C-peptide (0.2–0.9 ng/ml) was detected in the serum of islet recipients throughout the study period. No differences were detected between recipient animals receiving islet macrobeads of various ages. These results demonstrate that the encapsulation of porcine islets in agarose macrobeads allows for extended culture periods and is an appropriate strategy for functional and microbiological assessment prior to clinical use.
Autologous Transplantation of Muscle-Derived CD133+ Stem Cells in Duchenne Muscle Patients
Authors: Torrente Y. , Belicchi M. , Marchesi C. , D'antona G. , Cogiamanian F. , Pisati F. , Gavina M. , Giordano R. , Tonlorenzi R. , Fagiolari G. , Lamperti C. , Porretti L. , Lopa R. , Sampaolesi M. , Vicentini L. , Grimoldi N. , Tiberio F. , Songa V. , Baratta P. , Prelle A. , Forzenigo L. , Guglieri M. , Pansarasa O. , Rinaldi C. , Mouly V. , Butler-Browne G. S. , Comi G. P. , Biondetti P. , Moggio M. , Gaini S. M. , Stocchetti N. , Priori A. , D'angelo M. G. , Turconi A. , Bottinelli R. , Cossu G. , Rebulla P. , Bresolin N.
Published: September 2014

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.
A Closed System for Islet Isolation and Purification Using the COBE2991 Cell Processor May Reduce the Need of Clean Room Facilities
Authors: Klaffschenkel R. A. , Biesemeier A. , Waidmann M. , Northoff H. , Steurer W. , Königsrainer A. , Lembert N.
Published: September 2014

During the isolation of human islets of Langerhans the digest has repeated direct contact with the ambient atmosphere. In order to fulfill GMP requirements in clinical applications, the entire cell preparation must be performed in clean room facilities. We hypothesized that the use of a closed system, which avoids the direct exposure of tissue to the atmosphere, would significantly ease the preparation procedure. To avoid the direct atmosphere exposure we tested a modification of the isolation and purification process by performing all islet preparation steps in a closed system. In this study we compared the isolation outcome of the traditional open preparation technique with the new closed system. Pancreata from 6-month-old hybrid pigs were procured in the local slaughterhouse. After digestion/filtration the digest was cooled, collected, and concentrated in centrifugation containers and purified thereafter in the COBE2991 by top loading (control). In the control group 502 ± 253 IEQ per gram pancreas were purified. The total preparation time amounted to 12 h. In the closed system the digest was cooled and directly pumped into the COBE2991 for centrifugation followed by supernatant expelling. Bag filling, centrifugation, and expelling were repeated several times. Islets in pellet form were than purified by adding a gradient (bottom loading). Using this closed system 1098 ± 489 IEQ per gram pancreas were purified with a total cell viability of 67 ± 10% and a β-cell viability of 41 ± 13%. The total preparation time reduced to 6 h. After 24 h of cell culture the viability of β-cells was still 56 ± 10% and was only reduced after the addition of proapoptotic IL-1 and TNF-α to 40 ± 4%, indicating that freshly isolated islets are not apoptotic. In conclusion, the closed system preparation is much faster, more effective, and less expensive than the traditional islet preparation. The closed system may be applicable for human islets preparations to restrict the need of clean room facilities for islet preparations to a minimum and may open the way for islet preparations without clean room demand.
Expression of Transforming Growth Factor-β by Human Islets: Impact on Islet Viability and Function
Authors: Sabek Omaima M. , Fraga Daniel W. , Henry James , Gaber Lillian W. , Kotb Malak , Gaber A. Osama
Published: September 2014

Transforming growth factor-β1 (TGF-β1) is a pleotropic cytokine that promotes angiogenesis and extracellular matrix protein synthesis in addition to its immunosuppressive effects. The purpose of this study is to identify optimal conditions for in vivo expression of TGF-β1 by human islets to exploit the possible beneficial effects and minimize undesirable side effects. We transduced human islets with adenoviral vectors encoding the active form of Ad-TGF-β1 or Ad-LacZ to test the effects of TGF-β1 gene expression on islet in vivo function following their transplantation into a NOD-SCID mouse model. Islets were transduced with multiplicity of infection (MOI) of 20, 10, 5, and 2.5 per islet cell. At a MOI ranging from 2.5 to 20, expression of TGF-β1 in islet supernatant persisted for 1–2 months and ranged from 153 ± 5 to 2574 ± 1299 pg/ml, respectively. Transduction with the lowest MOI (2.5) did not compromise the in vivo production of human C-peptide. We conclude that TGF-β1 expression in transplanted islets does not compromise viability and that adenoviral transduction with the TGF-β1 gene has a dose-dependent effect, with larger MOIs being deleterious. The data also indicate that in vitro culture system and the in vivo NOD-SCID model could be used successfully to evaluate the nonimmune effects of gene transduction.
Efficient Intracytoplasmic Labeling of Human Umbilical Cord Blood Mesenchymal Stromal Cells with Ferumoxides
Authors: Lee Jae Kwon , Lee Man Kyoung , Jin Hye Jin , Kim Dal-Soo , Yang Yoon Sun , Oh Wonil , Yang Sung-Eun , Park Tae Seok , Lee Soo Yeol , Kim Bum-Soo , Jeun Sin-Soo
Published: September 2014

Mesenchymal stromal cells (MSCs) are multipotent cells found in several adult tissues; they have the capacity to differentiate into mesodermal, ectodermal, and endodermal tissues in vitro. There have been several reports that MSCs have therapeutic effects in a variety of diseases. Therefore, using a cell labeling technique, monitoring their temporal and spatial migration in vivo, would be useful in the clinical setting. Magnetic resonance imaging (MRI)—tracking of superparamagnetic iron oxide (SPIO)-labeled cells—is a noninvasive technique for determining the location and migration of transplanted cells. In the present study, we evaluated the influence and toxicity of SPIO (ferumoxides) labeling on multiple differentiated MSCs. To evaluate the influence and toxicity of ferumoxides labeling on differentiation of MSCs, a variety of concentrations of ferumoxides were used for labeling MSCs. We found that the cytoplasm of adherent cells was effectively labeled at low concentrations of ferumoxides. Compared with unlabeled controls, the ferumoxides-labeled MSCs exhibited a similar proliferation rate and apoptotic progression. The labeled MSCs differentiated into osteoblasts and adipocytes in an identical fashion as the unlabeled cells. However, chondrogenesis and neurogenesis were inhibited at high concentrations of ferumoxides. Our results suggest the effective concentration for ferumoxides use in tracking MSCs.
Meiotic sex ratio variation in natural populations of Ceratodon purpureus (Ditrichaceae)
Authors: Norrell Tatum E. , Jones Kelly S. , Payton Adam C. , McDaniel Stuart F.
Published: September 2014

• Premise of study: Sex ratio variation is a common but often unexplained phenomenon in species across the tree of life. Here we evaluate the hypothesis that meiotic sex ratio variation can contribute to the biased sex ratios found in natural populations of the moss Ceratodon purpureus.

• Methods: We obtained sporophytes from several populations of C. purpureus from eastern North America. From each sporophyte, we estimated the mean spore viability by germinating replicate samples on agar plates. We estimated the meiotic sex ratio of each sporophyte by inferring the sex of a random sample of germinated spores (mean = 77) using a PCR‐RFLP test. We tested for among‐sporophyte variation in viability using an ANOVA and for deviations from 1:1 sex ratio using a χ2‐test and evaluated the relationship between these quantities using a linear regression.

• Key results: We found among‐sporophyte variation in spore viability and meiotic sex ratio, suggesting that genetic variants that contribute to variation in both of these traits segregate within populations of this species. However, we found no relationship between these quantities, suggesting that factors other than sex ratio distorters contribute to variation in spore viability within populations.

• Conclusions: These results demonstrate that sex ratio distortion may partially explain the population sex ratio variation seen in C. purpureus, but more generally that genetic conflict over meiotic segregation may contribute to fitness variation in this species. Overall, this study lays the groundwork for future studies on the genetic basis of meiotic sex ratio variation.
The first fossil of a bolbitidoid fern belongs to the early‐divergent lineages of Elaphoglossum (Dryopteridaceae)
Authors: Lóriga Josmaily , Schmidt Alexander R. , Moran Robbin C. , Feldberg Kathrin , Schneider Harald , Heinrichs Jochen
Published: September 2014

• Premise of the study: Closing gaps in the fossil record and elucidating phylogenetic relationships of mostly incomplete fossils are major challenges in the reconstruction of the diversification of fern lineages through time. The cosmopolitan family Dryopteridaceae represents one of the most species‐rich families of leptosporangiate ferns, yet its fossil record is sparse and poorly understood. Here, we describe a fern inclusion in Miocene Dominican amber and investigate its relationships to extant Dryopteridaceae.

• Methods: The morphology of the fossil was compared with descriptions of extant ferns, resulting in it being tentatively assigned to the bolbitidoid fern genus Elaphoglossum. This assignment was confirmed by reconstructing the evolution of the morphological characters preserved in the inclusion on a molecular phylogeny of 158 extant bolbitidoid ferns. To assess the morphology‐based assignment of the fossil to Elaphoglossum, we examined DNA‐calibrated divergence time estimates against the age of the amber deposits from which it came.

• Key results: The fossil belongs to Elaphoglossum and is the first of a bolbitidoid fern. Its assignment to a particular section of Elaphoglossum could not be determined; however, sects. Lepidoglossa, Polytrichia, and Setosa can be discounted because the fossil lacks subulate scales or scales with acicular marginal hairs. Thus, the fossil might belong to either sects. Amygdalifolia, Wrightiana, Elaphoglossum, or Squamipedia or to an extinct lineage.

• Conclusions: The discovery of a Miocene Elaphoglossum fossil provides remarkable support to current molecular clock‐based estimates of the diversification of these ferns.
La vie publique de l'enfant
Authors: Breviglieri Marc
Published: September 2014

Une première partie invite le lecteur à retrouver la question que pose Arendt à propos de l’ambigu pouvoir que la modernité lègue à l’enfant, ouvrant la réflexion sur une anthropologie capacitaire de la participation. Une seconde partie cherche à caractériser la nature et l’étendue des registres d’appréhension et d’expressivité dont l’enfant se montre capable lorsque son mode d’existence s’imprègne de présences et de valeurs publiques. Ce texte entend travailler sur un paradoxe : le mouvement d’élargissement participatif qui voudrait permettre à tous les enfants de prendre part au public contribue simultanément à appauvrir en un sens leur expérience de la vie publique. Ce paradoxe éclaire une forme de réduction anthropologique violente qui s’impose à l’enfance par le format de communication que suppose l’injonction contemporaine à prendre part à un public libéral.
Féminisme, participation politique des femmes et « publics contestataires » : dépasser la dichotomie privé-public et penser les liens du local au global
Authors: Giraud Isabelle
Published: September 2014

La recherche sur le féminisme et les diverses formes de militantisme qui lui sont attachées nécessite de dépasser la dichotomie privé-public comme d’articuler les diverses échelles de luttes sur des terrains d’enquête localisés. La création d’un agenda de recherche à partir du concept de « publics contestataires » par L. Phillips, S. Cole et leurs étudiantes M.-E. Carrier-Moisan et E. Lagalisse dans l’ouvrage Contesting Publics. Feminism, Activism, Ethnography (Pluto Press, 2013) semble prometteuse au regard de ces deux enjeux. Toutefois, la mise en œuvre de cette approche sur leurs terrains respectifs en Amérique latine, à travers le concept de « publics contestataires », révèle des effets générationnels, les plus jeunes développant plus aisément une approche intersectionnelle qui dépasse l’opposition privé-public. Nous constatons également des biais professionnels, les chercheuses des deux générations démontrant une certaine difficulté à intégrer l’échelle transnationale dans leur analyse, alors que, par ailleurs, l’ouvrage présente tels quels des témoignages de militantes qui n’ont de cesse de rappeler l’importance des réseaux féministes transnationaux.
Cartographie critique des objections historicistes à la centralité du travail
Authors: Deranty Jean-Philippe
Published: September 2014

Les objections à la centralité du travail prennent appui sur une présupposition historique massive et souvent non questionnée, selon laquelle le travail n’est devenu une institution centrale qu’avec l’avènement de la modernité capitaliste occidentale. Cet article pose les premiers jalons d’une cartographie critique de cet arrière-plan historiciste aux objections à la centralité du travail. L’identification des références constitutives de ce champ permet de démêler l’écheveau des arguments impliqués, et de les soumettre à une double critique : sur le plan empirique d’abord, puisque les recherches historiques et ethnologiques spécialisées tendent à démontrer la persistance de la centralité psychologique et sociopolitique du travail à travers les sociétés les plus diverses. À partir de ce matériau historique, une contre-image de la signification anthropologique du travail se dégage qui place ce dernier au cœur de l’ontologie sociale. Summmary , p. 47. Resumen , p. 47.
Work as Expression
Authors: Smith Nicholas H.
Published: September 2014

Cet article replace la conception du travail développée par la psychodynamique du travail dans la tradition philosophique de l’expressivisme et soutient la primauté de la conception expressiviste du travail sur la conception classique du travail comme poiesis . À l’issue d’une reconstruction des arguments principaux portant sur l’opposition entre poiesis (travail de production) et praxis (action morale), l’attention sera portée sur les limites de ce modèle de conceptualisation du travail. Un modèle alternatif est introduit à partir de la prise en compte de plusieurs dimensions du concept d’expression utilisé dans le langage courant. Cela nous permet de mettre en évidence ce qui, dans le modèle psychodynamique de C. Dejours, est précisément « expressiviste ». Une fois l’origine expressiviste de la théorie de Dejours établie, plusieurs interprétations des normes d’expression sont présentées, en lien avec l’évaluation des organisations du travail contemporaines.
Synthesis and mechanical properties of a calcium sulphoaluminate cement made of industrial wastes
Authors: Gallardo M. , Almanza J. M. , Cortés D. A. , Escobedo J. C. , Escalante-García J. I.
Published: September 2014

Environmentally-friendly calcium sulphoaluminate clinkers were obtained from a mixture of aluminium dross, fluorgypsum, fly ash and CaCO₃ at temperatures within the range of 1100 to 1400 °C. After the heat treatments Ca₄Al₆O₁₂SO₄ was the main phase. Three different cements were prepared using the clinkers synthesized at 1250, 1350 and 1400 °C; the clinker powders were mixed with 20 wt% of hemihydrate. Cement pastes were prepared using a water/cement ratio (w/c), 0.4 followed by curing at 20 or 40 °C for periods of time ranging from 1 to 28 days. Most of the samples showed high compression strengths 40–47 MPa after 28 days, which were comparable to the strength of Portland cement. Ettringite was the main hydration product and its morphology consisted of acicular and hexagonal plates, which is typical of this phase.
Analysis of Various Structures of Standards Setting Organizations (SSOs) That Impact Tension among Members
Authors: Seo DongBack
Published: September 2014

As the field of ICT standardization has changed from a relatively static, monolithic environment into a very dynamic field in the last two decades, many formal standardization bodies, fora, consortia, and other types of Standards Setting Organizations (SSOs) have emerged. These SSOs have often competed against each other for the same application areas. To a large degree, these changes reflect developments in the field of telecommunications and IT themselves, including liberalization, globalization, rapid changes in technology, and convergence. More than ever before, firms can choose which standard setting body they want to join. Nevertheless, data shows that many firms decide to be members of many relevant bodies at the same time. The aforementioned changes and the multi-SSO memberships of a firm have differently influenced various types of stakeholders, which increases potential tension among members during standardization processes. This chapter intends to study such tension and the effect influenced by the structure and processes of the standard-setting bodies themselves. A framework to analyze tension within given organizational structure and processes based on Giddens' Structuration Theory is proposed. The appealing feature of this theory is that it is neither deterministic at the agent level nor at the structural level, but takes iterative influences between both levels as a starting point. This study shows how an SSO struggles to decrease tension among members and suggests propositions related to the tension that academia and practitioners can apply.
Standards for ICT
Authors: Egyedi Tineke , Muto Sachiko
Published: September 2014

This chapter analyzes standardization of mobile phone chargers to explore the role that compatibility standards might play in mitigating the negative impact of ICT on the environment. Building on insights gained from the economics of standards literature, the authors explore how the inherent effects of compatibility standards—such as reducing variety, avoiding lock-in, and building critical mass—can have positive implications for the environment. They argue that current standardization literature and policy have overlooked this important (side) effect of compatibility standards. Excessive diversity and incompatibilities in ICT generate e-waste, discourage re-use, and make recycling economically unviable; the authors, therefore, develop an economic-environmental framework for analyzing sustainability effects of compatibility standards and apply it to the case of mobile phone chargers. They conclude that well-targeted compatibility standardization can be equated to ecodesign at sector level and should be considered as an eco-effective strategy towards greening the IT industry.
Achieving Standardization
Authors: Henningsson Stefan
Published: September 2014

International e-Customs is going through a standardization process. Driven by the need to increase control in the trade process to address security challenges stemming from threats of terrorists, diseases, and counterfeit products, and to lower the administrative burdens on traders to stay competitive, national customs and regional economic organizations are seeking to establish a standardized solution for digital reporting of customs data. However, standardization has proven hard to achieve in the socio-technical e-Customs solution. In this chapter, the authors identify and describe what has to be harmonized in order for a global company to perceive e-Customs as standardized. In doing so, they contribute an explanation of the challenges associated with using a standardization mechanism for harmonizing socio-technical information systems.
Standards Development as Hybridization and Capacity Building
Authors: Shen Xiaobai , Graham Ian , Williams Robin
Published: September 2014

While users in the rest of the world have been offered 3G mobile phones based on either the CDMA2000 or W-CDMA standards, users in China have the additional option of using phones based on the TD-SCDMA standard. As a technology largely developed by Chinese actors and only implemented in China, TD-SCDMA has been seen as an “indigenous innovation” orchestrated by the Chinese government and supported by Chinese firms. China's support for TD-SCDMA was widely viewed in the West as a ploy to keep the “global” 3G standards, W-CDMA and CDMA2000, out of China, but in 2009, the Chinese government licensed the operation of all three standards. The authors argue that Chinese support for TD-SCDMA, rather than being a defensive move, was a proactive policy to use the TD-SCDMA standard to develop Chinese industrial capacity, which could then be fed back into the global processes developing later generations of telecommunications standards. Rather than being an indigenous Chinese technology, TD-SCDMA's history exemplifies how standards and the intellectual property and technological know-how embedded in them lead to a complex hybridization between the global and national systems of innovation.
The Role of the Individual in ICT Standardisation
Authors: Jakobs Kai
Published: September 2014

This chapter discusses the influence individuals have in the ICT standards development process. The chapter draws upon ideas underlying the theory of the Social Shaping of Technology (SST). Looking through the SST lens, a number of non-technical factors that influence ICT standards development are identified. A literature review on the role of the individual in ICT standards setting and a case study of the IEEE 802.11 Working Group (WG) show that in a standards body's WG, the backgrounds, skills, attitudes, and behaviour of the individual WG members are crucially important factors. Yet, the case study also shows that in most cases employees tend to represent the ideas and goals of their respective employer. The chapter observes that the non-technical factors are ignored all too often in the literature. It argues that a better understanding of the impact and interplay of these factors, specifically including the skills and attitudes of the WG members, will have significant implications both theoretical and managerial.
How to Implement Standardization Education in a Country
Authors: de Vries Henk J.
Published: September 2014

This chapter explores how standardization education can be implemented at the national level. Previous studies form the main source for the chapter. This research shows that implementation of standardization in the national education system requires a national policy, a long-term investment in support, and cooperation between industry, standardization bodies, academia, other institutions involved in education, and government. The approach should combine bottom-up and top-down. The chapter is new in combining previous findings to an underpinned recommendation on how to implement standardization education.
A Migration Approach for Fault Tolerance in Cloud Computing
Authors: Limam Said , Belalem Ghalem
Published: September 2014

Cloud computing has become a significant technology and a great solution for providing a flexible, on-demand, and dynamically scalable computing infrastructure for many applications. Cloud computing also presents a significant technology trends. With the cloud computing technology, users use a variety of devices to access programs, storage, and application-development platforms over the Internet, via services offered by cloud computing providers. The probability of failure occur during the execution becomes stronger when the number of node increases; since it is impossible to fully prevent failures, one solution is to implement fault tolerance mechanisms. Fault tolerance has become a major task for computer engineers and software developers because the occurrence of faults increases the cost of using resources. In this paper, the authors have proposed an approach that is a combination of migration and checkpoint mechanism. The checkpoint mechanism minimizes the time lost and reduces the effect of failures on application execution while the migration mechanism guarantee the continuity of application execution and avoid any loss due to hardware failure in a way transparent and efficient. The results obtained by the simulation show the effectiveness of our approaches to fault tolerance in term of execution time and masking effects of failures.