Induced Pluripotent Stem Cells Can Be Used to Model the Genomic Imprinting Disorder Prader-Willi Syndrome*

PubMed Central

Yang, Jiayin; Cai, Jie; Zhang, Ya; Wang, Xianming; Li, Wen; Xu, Jianyong; Li, Feng; Guo, Xiangpeng; Deng, Kang; Zhong, Mei; Chen, Yonglong; Lai, Liangxue; Pei, Duanqing; Esteban, Miguel A.

2010-01-01

The recent discovery of induced pluripotent stem cell (iPSC) technology provides an invaluable tool for creating in vitro representations of human genetic conditions. This is particularly relevant for those diseases that lack adequate animal models or where the species comparison is difficult, e.g. imprinting diseases such as the neurogenetic disorder Prader-Willi syndrome (PWS). However, recent reports have unveiled transcriptional and functional differences between iPSCs and embryonic stem cells that in cases are attributable to imprinting errors. This has suggested that human iPSCs may not be useful to model genetic imprinting diseases. Here, we describe the generation of iPSCs from a patient with PWS bearing a partial translocation of the paternally expressed chromosome 15q11-q13 region to chromosome 4. The resulting iPSCs match all standard criteria of bona fide reprogramming and could be readily differentiated into tissues derived from the three germ layers, including neurons. Moreover, these iPSCs retain a high level of DNA methylation in the imprinting center of the maternal allele and show concomitant reduced expression of the disease-associated small nucleolar RNA HBII-85/SNORD116. These results indicate that iPSCs may be a useful tool to study PWS and perhaps other genetic imprinting diseases as well. PMID:20956530

Evaluating Psychosocial Mechanisms Underlying STEM Persistence in Undergraduates: Evidence of Impact from a Six-Day Pre–College Engagement STEM Academy Program

PubMed Central

Findley-Van Nostrand, Danielle; Pollenz, Richard S.

2017-01-01

The persistence of undergraduate students in science, technology, engineering, and mathematics (STEM) disciplines is a national issue based on STEM workforce projections. We implemented a weeklong pre–college engagement STEM Academy (SA) program aimed at addressing several areas related to STEM retention. We validated an instrument that was developed based on existing, validated measures and examined several psychosocial constructs related to STEM (science identity, self-efficacy, sense of belonging to the university and to STEM, career expectancies, and intention to leave STEM majors) before and after the program. We also compared students in the SA program with a matched comparison group of first-year students. Results show that SA students significantly increased in science identity and sense of belonging to STEM and to the university, all predictive of increased STEM retention and a primary aim of the program. Relative to the matched comparison group, SA students began their first semester with higher STEM self-efficacy, sense of belonging, and science identity, positive career expectancies, and lower intention to leave STEM. The SA cohort showed 98% first-year retention and 92% STEM major retention. The SA program serves as a model of a scalable, first-level, cocurricular engagement experience to enhance psychosocial factors that impact undergraduate persistence in STEM. PMID:28572178

Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

PubMed Central

Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

2017-01-01

Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

Association of Physical and Technical Activities With Partial Match Status in a Soccer Professional Team.

PubMed

Moalla, Wassim; Fessi, Mohamed Saieffedin; Makni, Emna; Dellal, Alexandre; Filetti, Cristoforo; Di Salvo, Valter; Chamari, Karim

2018-06-01

Moalla, W, Fessi, MS, Makni, E, Dellal, A, Filetti, C, Di Salvo, V, and Chamari, K. Association of physical and technical activities with partial match status in a soccer professional team. J Strength Cond Res 32(6): 1708-1714, 2018-The purpose of this study was to examine the association between physical and technical activities and partial match status (winning, drawing, or losing) in a professional soccer team over 2 seasons. Physical and technical activities of 52 official matches were collected and analyzed at each 15-minute interval, for each half (45 minutes), and full match (90 minutes) using a multiple-camera computerized tracking system. The results indicated that according to full match outcome: winning status was characterized by players covering more total distance (p ≤ 0.05) and low-intensity running (<14.4 km·h) (p ≤ 0.05), whereas, losing status induced more sprinting (≥25.2 km·h) (p < 0.01) and high-intensity running (≥19.8 km·h) (p ≤ 0.05). However, according to partial match status (i.e., 15 minutes and half time), players covered more distance for all running intensities while winning (p < 0.01). Technical match performance scores were not influenced by match status. In conclusion, the present study showed that the physical activities including high-intensity running and total distance covered were related to the match status, whereas technical activities were not. The overall outcome shows that higher physical activity was associated with winning partial match periods. This approach highlights the importance of physical fitness in soccer and may help coaches to better modulate players' roles and team tactical organization throughout the match.

Oxygen Effect on the Properties of Epitaxial (110) La0.7Sr0.3MnO3 by Defect Engineering.

PubMed

Rasic, Daniel; Sachan, Ritesh; Temizer, Namik K; Prater, John; Narayan, Jagdish

2018-06-20

The multiferroic properties of mixed valence perovskites such as lanthanum strontium manganese oxide (La 0.7 Sr 0.3 MnO 3 ) (LSMO) demonstrate a unique dependence on oxygen concentration, thickness, strain, and orientation. To better understand the role of each variable, a systematic study has been performed. In this study, epitaxial growth of LSMO (110) thin films with thicknesses ∼15 nm are reported on epitaxial magnesium oxide (111) buffered Al 2 O 3 (0001) substrates. Four LSMO films with changing oxygen concentration have been investigated. The oxygen content in the films was controlled by varying the oxygen partial pressure from 1 × 10 -4 to 1 × 10 -1 Torr during deposition and subsequent cooldown. X-ray diffraction established the out-of-plane and in-plane plane matching to be (111) MgO ∥ (0001) Al 2 O 3 and ⟨11̅0⟩ MgO ∥ ⟨101̅0⟩ Al 2 O 3 for the buffer layer with the substrate, and an out-of-plane lattice matching of (110) LSMO ∥ (111) MgO for the LSMO layer. For the case of the LSMO growth on MgO, a novel growth mode has been demonstrated, showing that three in-plane matching variants are present: (i) ⟨11̅0⟩ LSMO ∥ ⟨11̅0⟩ MgO , (ii) ⟨11̅0⟩ LSMO ∥ ⟨101̅⟩ MgO , and (iii) ⟨11̅0⟩ LSMO ∥ ⟨01̅1⟩ MgO . The atomic resolution scanning transmission electron microscopy (STEM) images were taken of the interfaces that showed a thin, ∼2 monolayer intermixed phase while high-angle annular dark field (HAADF) cross-section images revealed 4/5 plane matching between the film and the buffer and similar domain sizes between different samples. Magnetic properties were measured for all films and the gradual decrease in saturation magnetization is reported with decreasing oxygen partial pressure during growth. A systematic increase in the interplanar spacing was observed by X-ray diffraction of the films with lower oxygen concentration, indicating the decrease in the lattice constant in the plane due to the point defects. Samples demonstrated an insulating behavior for samples grown under low oxygen partial pressure and semiconducting behavior for the highest oxygen partial pressures. Magnetotransport measurements showed ∼36.2% decrease in electrical resistivity with an applied magnetic field of 10 T at 50 K and ∼1.3% at room temperature for the highly oxygenated sample.

A comparison between placental and amniotic mesenchymal stem cells for transamniotic stem cell therapy (TRASCET) in experimental spina bifida.

PubMed

Feng, Christina; D Graham, Christopher; Connors, John Patrick; Brazzo, Joseph; Zurakowski, David; Fauza, Dario O

2016-06-01

We compared placental-derived and amniotic fluid-derived mesenchymal stem cells (pMSCs and afMSCs, respectively) in transamniotic stem cell therapy (TRASCET) for experimental spina bifida. Pregnant dams (n=29) exposed to retinoic acid for the induction of fetal spina bifida were divided into four groups. Three groups received volume-matched intraamniotic injections of either saline (n=38 fetuses) or a suspension of 2×10(6) cells/mL of syngeneic, labeled afMSCs (n=73) or pMSCs (n=115) on gestational day 17 (term=21-22days). Untreated fetuses served as controls. Animals were killed before term. Statistical comparisons were by Fisher's exact test (p<0.05). Survival was similar across treatment groups (p=0.08). In fetuses with isolated spina bifida (n=100), there were higher percentages of defect coverage (either partial or complete) in both afMSC and pMSC groups compared with saline and untreated groups (p<0.001-0.03 in pairwise comparisons). There were no differences in coverage rates between afMSC and pMSC groups (p=0.94) or between saline and untreated groups (p=0.98). Both pMSC and afMSC can induce comparable rates of coverage of experimental spina bifida after concentrated intraamniotic injection in the rodent model. This broadens the options for timing and cell source for TRASCET as a potential alternative in the prenatal management of spina bifida. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated matching of multiple terrestrial laser scans for stem mapping without the use of artificial references

NASA Astrophysics Data System (ADS)

Liu, Jingbin; Liang, Xinlian; Hyyppä, Juha; Yu, Xiaowei; Lehtomäki, Matti; Pyörälä, Jiri; Zhu, Lingli; Wang, Yunsheng; Chen, Ruizhi

2017-04-01

Terrestrial laser scanning has been widely used to analyze the 3D structure of a forest in detail and to generate data at the level of a reference plot for forest inventories without destructive measurements. Multi-scan terrestrial laser scanning is more commonly applied to collect plot-level data so that all of the stems can be detected and analyzed. However, it is necessary to match the point clouds of multiple scans to yield a point cloud with automated processing. Mismatches between datasets will lead to errors during the processing of multi-scan data. Classic registration methods based on flat surfaces cannot be directly applied in forest environments; therefore, artificial reference objects have conventionally been used to assist with scan matching. The use of artificial references requires additional labor and expertise, as well as greatly increasing the cost. In this study, we present an automated processing method for plot-level stem mapping that matches multiple scans without artificial references. In contrast to previous studies, the registration method developed in this study exploits the natural geometric characteristics among a set of tree stems in a plot and combines the point clouds of multiple scans into a unified coordinate system. Integrating multiple scans improves the overall performance of stem mapping in terms of the correctness of tree detection, as well as the bias and the root-mean-square errors of forest attributes such as diameter at breast height and tree height. In addition, the automated processing method makes stem mapping more reliable and consistent among plots, reduces the costs associated with plot-based stem mapping, and enhances the efficiency.

Security and matching of partial fingerprint recognition systems

NASA Astrophysics Data System (ADS)

Jea, Tsai-Yang; Chavan, Viraj S.; Govindaraju, Venu; Schneider, John K.

2004-08-01

Despite advances in fingerprint identification techniques, matching incomplete or partial fingerprints still poses a difficult challenge. While the introduction of compact silicon chip-based sensors that capture only a part of the fingerprint area have made this problem important from a commercial perspective, there is also considerable interest on the topic for processing partial and latent fingerprints obtained at crime scenes. Attempts to match partial fingerprints using singular ridge structures-based alignment techniques fail when the partial print does not include such structures (e.g., core or delta). We present a multi-path fingerprint matching approach that utilizes localized secondary features derived using only the relative information of minutiae. Since the minutia-based fingerprint representation, is an ANSI-NIST standard, our approach has the advantage of being directly applicable to already existing databases. We also analyze the vulnerability of partial fingerprint identification systems to brute force attacks. The described matching approach has been tested on one of FVC2002"s DB1 database11. The experimental results show that our approach achieves an equal error rate of 1.25% and a total error rate of 1.8% (with FAR at 0.2% and FRR at 1.6%).

Alternative donor transplantation for adults with acute leukemia.

PubMed

Appelbaum, Frederick R

2014-01-01

Allogeneic hematopoietic cell transplantation (HCT) from a matched related donor (MRD) is the preferred therapy for many adults with acute leukemia. Yet most patients do not have matched siblings, and the numbers who do will continue to drop as the average number of children per couple in the United States continues to decline. Recent reports show little difference in the outcomes of matched related and matched unrelated transplants for acute leukemia. Additionally, survival rates at 3-5 years after transplant appear to be generally similar following matched related, matched unrelated, single antigen mismatched unrelated, double cord blood and, perhaps even after haplo-identical transplants. Nevertheless, there are differences between stem cell sources that should be considered in the choice of donor. The following review provides some perspective on the identification of the best stem cell sources for patients who do not have matches within their families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predicting College Readiness in STEM: A Longitudinal Study of Iowa Students

ERIC Educational Resources Information Center

Rickels, Heather Anne

2017-01-01

The demand for STEM college graduates is increasing. However, recent studies show there are not enough STEM majors to fulfill this need. This deficiency can be partially attributed to a gender discrepancy in the number of female STEM graduates and to the high rate of attrition of STEM majors. As STEM attrition has been associated with students…

Conversion of partially reprogrammed cells to fully pluripotent stem cells is associated with further activation of stem cell maintenance- and gamete generation-related genes.

PubMed

Kim, Jong Soo; Choi, Hyun Woo; Choi, Sol; Seo, Han Geuk; Moon, Sung-Hwan; Chung, Hyung-Min; Do, Jeong Tae

2014-11-01

Somatic cells are reprogrammed to induced pluripotent stem cells (iPSCs) by overexpression of a combination of defined transcription factors. We generated iPSCs from mouse embryonic fibroblasts (with Oct4-GFP reporter) by transfection of pCX-OSK-2A (Oct4, Sox2, and Klf4) and pCX-cMyc vectors. We could generate partially reprogrammed cells (XiPS-7), which maintained more than 20 passages in a partially reprogrammed state; the cells expressed Nanog but were Oct4-GFP negative. When the cells were transferred to serum-free medium (with serum replacement and basic fibroblast growth factor), the XiPS-7 cells converted to Oct4-GFP-positive iPSCs (XiPS-7c, fully reprogrammed cells) with ESC-like properties. During the conversion of XiPS-7 to XiPS-7c, we found several clusters of slowly reprogrammed genes, which were activated at later stages of reprogramming. Our results suggest that partial reprogrammed cells can be induced to full reprogramming status by serum-free medium, in which stem cell maintenance- and gamete generation-related genes were upregulated. These long-term expandable partially reprogrammed cells can be used to verify the mechanism of reprogramming.

How to select the best available related or unrelated donor of hematopoietic stem cells?

PubMed

Tiercy, Jean-Marie

2016-06-01

Recognition of HLA incompatibilities by the immune system represents a major barrier to allogeneic hematopoietic stem cell transplantation. HLA genotypically identical sibling donors are, therefore, the gold standard for transplantation purposes, but only 30% patients have such a donor. For the remaining 70% patients alternative sources of stem cells are a matched unrelated adult volunteer donor, a haploidentical donor or a cord blood unit. The definition of 'HLA matching' depends on the level of resolution and on which loci are tested. The development of HLA molecular typing technologies and the availability of more than 27 million donors in the international database has greatly facilitated unrelated donor searches. The gold standard is high resolution typing at the HLA-A, -B, -C, -DRB1, and -DQB1 loci (10/10 match). Single disparities for HLA-A, -B, - C, or -DRB1 are associated with increased risk of post-transplant complications, but less so in patients with advanced disease, and in those undergoing T-cell-depleted allografting. HLA-DQB1 mismatches seem to be better tolerated and some HLA-C, -DRB1 and -DPB1 disparities are potentially less immunogenic. HLA typing by next-generation sequencing methods is likely to change matching algorithms by providing full sequence information on all HLA loci in a single step. In most European populations a 10/10 matched donor can be found for at least 50% of patients and an additional 20-30% patients may have a 9/10 matched donor. Genetic factors that help in identifying donors with less immunogenic mismatches are discussed. Haploidentical donors are increasingly used as an alternative source of stem cells for those patients lacking a matched unrelated donor. Copyright© Ferrata Storti Foundation.

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey.

PubMed

Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül

2017-12-01

Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

Robot-assisted laparoscopic partial nephrectomy versus laparoscopic partial nephrectomy: A propensity score-matched comparative analysis of surgical outcomes and preserved renal parenchymal volume.

PubMed

Tachibana, Hidekazu; Takagi, Toshio; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

2018-04-01

To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot-assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score-matched analyses. In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot-assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients' background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. After matching, 64 patients were assigned to each group. The mean age was 56-57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4-7). The incidence rate of acute kidney failure was significantly lower in the robot-assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot-assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post-surgery was 96% for robot-assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot-assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Robot-assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. © 2018 The Japanese Urological Association.

Formulating an image matching strategy for terrestrial stem data collection using a multisensor video system

Treesearch

Neil A. Clark

2001-01-01

A multisensor video system has been developed incorporating a CCD video camera, a 3-axis magnetometer, and a laser-rangefinding device, for the purpose of measuring individual tree stems. While preliminary results show promise, some changes are needed to improve the accuracy and efficiency of the system. Image matching is needed to improve the accuracy of length...

CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway

PubMed Central

Jijiwa, Mayumi; Demir, Habibe; Gupta, Snehalata; Leung, Crystal; Joshi, Kaushal; Orozco, Nicholas; Huang, Tiffany; Yildiz, Vedat O.; Shibahara, Ichiyo; de Jesus, Jason A.; Yong, William H.; Mischel, Paul S.; Fernandez, Soledad; Kornblum, Harley I.; Nakano, Ichiro

2011-01-01

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44high GBM but not from CD44low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44high GBM, but not in CD44low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKTpathway. PMID:21915300

Degenerate RNA packaging signals in the genome of Satellite Tobacco Necrosis Virus: implications for the assembly of a T=1 capsid.

PubMed

Bunka, David H J; Lane, Stephen W; Lane, Claire L; Dykeman, Eric C; Ford, Robert J; Barker, Amy M; Twarock, Reidun; Phillips, Simon E V; Stockley, Peter G

2011-10-14

Using a recombinant, T=1 Satellite Tobacco Necrosis Virus (STNV)-like particle expressed in Escherichia coli, we have established conditions for in vitro disassembly and reassembly of the viral capsid. In vivo assembly is dependent on the presence of the coat protein (CP) N-terminal region, and in vitro assembly requires RNA. Using immobilised CP monomers under reassembly conditions with "free" CP subunits, we have prepared a range of partially assembled CP species for RNA aptamer selection. SELEX directed against the RNA-binding face of the STNV CP resulted in the isolation of several clones, one of which (B3) matches the STNV-1 genome in 16 out of 25 nucleotide positions, including across a statistically significant 10/10 stretch. This 10-base region folds into a stem-loop displaying the motif ACAA and has been shown to bind to STNV CP. Analysis of the other aptamer sequences reveals that the majority can be folded into stem-loops displaying versions of this motif. Using a sequence and secondary structure search motif to analyse the genomic sequence of STNV-1, we identified 30 stem-loops displaying the sequence motif AxxA. The implication is that there are many stem-loops in the genome carrying essential recognition features for binding STNV CP. Secondary structure predictions of the genomic RNA using Mfold showed that only 8 out of 30 of these stem-loops would be formed in the lowest-energy structure. These results are consistent with an assembly mechanism based on kinetically driven folding of the RNA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance.

PubMed

Suzuki, Shuhei; Okada, Masashi; Kuramoto, Kenta; Takeda, Hiroyuki; Sakaki, Hirotsugu; Watarai, Hikaru; Sanomachi, Tomomi; Seino, Shizuka; Yoshioka, Takashi; Kitanaka, Chifumi

2016-10-01

There is a growing interest in repurposing antipsychotic dopamine antagonists for cancer treatment; however, antipsychotics are often associated with an increased risk of fatal events. The anticancer activities of aripiprazole, an antipsychotic drug with partial dopamine agonist activity and an excellent safety profile, remain unknown. The effects of aripiprazole alone or in combination with chemotherapeutic agents on the growth, sphere-forming ability and stem cell/differentiation/chemoresistance marker expression of cancer stem cells, serum-cultured cancer cells from which they were derived, and normal cells were examined. At concentrations non-toxic to normal cells, aripiprazole inhibited the growth of serum-cultured cancer cells and cancer stem cells. Furthermore, aripiprazole induced differentiation and inhibited sphere formation, as well as stem cell marker expression of cancer stem cells while inhibiting their survivin expression and sensitizing them to chemotherapeutic agents. Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Do Stem Taper Microgrooves Influence Taper Corrosion in Total Hip Arthroplasty? A Matched Cohort Retrieval Study.

PubMed

Arnholt, Christina M; MacDonald, Daniel W; Underwood, Richard J; Guyer, Eric P; Rimnac, Clare M; Kurtz, Steven M; Mont, Michael A; Klein, Gregg R; Lee, Gwo-Chin; Chen, Antonia F; Hamlin, Brian R; Cates, Harold E; Malkani, Arthur L; Kraay, Matthew J

2017-04-01

Previous studies identified imprinting of the stem morphology onto the interior head bore, leading researchers to hypothesize an influence of taper topography on mechanically assisted crevice corrosion. The purpose of this study was to analyze whether microgrooved stem tapers result in greater fretting corrosion damage than smooth stem tapers. A matched cohort of 120 retrieved head-stem pairs from metal-on-polyethylene bearings was created controlling for implantation time, flexural rigidity, apparent length of engagement, and head size. There were 2 groups of 60 heads each, mated with either smooth or microgrooved stem tapers. A high-precision roundness machine was used to measure and categorize the surface morphology. Fretting corrosion damage at the head-neck junction was characterized using the Higgs-Goldberg scoring method. Fourteen of the most damaged heads were analyzed for the maximum depth of material loss and focused ion beam cross-sectioned to view oxide and base metal. Fretting corrosion damage was not different between the 2 cohorts at the femoral head (P = .14, Mann-Whitney) or stem tapers (P = .35). There was no difference in the maximum depths of material loss between the cohorts (P = .71). Cross-sectioning revealed contact damage, signs of micro-motion, and chromium-rich oxide layers in both cohorts. Microgroove imprinting did not appear to have a different effect on the fretting corrosion behavior. The results of this matched cohort retrieval study do not support the hypothesis that taper surfaces with microgrooved stems exhibit increased in vivo fretting corrosion damage or material release. Copyright © 2016 Elsevier Inc. All rights reserved.

Preimplantation genetic diagnosis with HLA matching.

PubMed

Rechitsky, Svetlana; Kuliev, Anver; Tur-Kaspa, Illan; Morris, Randy; Verlinsky, Yury

2004-08-01

Preimplantation genetic diagnosis (PGD) has recently been offered in combination with HLA typing, which allowed a successful haematopoietic reconstitution in affected siblings with Fanconi anaemia by transplantation of stem cells obtained from the HLA-matched offspring resulting from PGD. This study presents the results of the first PGD practical experience performed in a group of couples at risk for producing children with genetic disorders. These parents also requested preimplantation HLA typing for treating the affected children in the family, who required HLA-matched stem cell transplantation. Using a standard IVF procedure, oocytes or embryos were tested for causative gene mutations simultaneously with HLA alleles, selecting and transferring only those unaffected embryos, which were HLA matched to the affected siblings. The procedure was performed for patients with children affected by Fanconi anaemia (FANC) A and C, different thalassaemia mutations, Wiscott-Aldrich syndrome, X-linked adrenoleukodystrophy, X-linked hyperimmunoglobulin M syndrome and X-linked hypohidrotic ectodermal displasia with immune deficiency. Overall, 46 PGD cycles were performed for 26 couples, resulting in selection and transfer of 50 unaffected HLA-matched embryos in 33 cycles, yielding six HLA-matched clinical pregnancies and the birth of five unaffected HLA-matched children. Despite the controversy of PGD use for HLA typing, the data demonstrate the usefulness of this approach for at-risk couples, not only to avoid the birth of affected children with an inherited disease, but also for having unaffected children who may also be potential HLA-matched donors of stem cells for treatment of affected siblings.

Typography manipulations can affect priming of word stem completion in older and younger adults.

PubMed

Gibson, J M; Brooks, J O; Friedman, L; Yesavage, J A

1993-12-01

The experiments reported here investigated whether changes of typography affected priming of word stem completion performance in older and younger adults. Across all experiments, the typeface in which a word appeared at presentation either did or did not match that of its 3-letter stem at test. In Experiment 1, no significant evidence of a typography effect was found when words were presented with a sentence judgment or letter judgment task. However, subsequent experiments revealed that, in both older and younger adults, only words presented with a syllable judgment task gave rise to the typography effect (Experiments 2-4). Specifically, performance was greater, when the presentation and test typeface matched than when they did not. Experiment 5, which used stem-cued recall, did not reveal a difference between syllable and letter judgment tasks. These findings highlight the complex nature of word stem completion performance.

Fast template matching with polynomials.

PubMed

Omachi, Shinichiro; Omachi, Masako

2007-08-01

Template matching is widely used for many applications in image and signal processing. This paper proposes a novel template matching algorithm, called algebraic template matching. Given a template and an input image, algebraic template matching efficiently calculates similarities between the template and the partial images of the input image, for various widths and heights. The partial image most similar to the template image is detected from the input image for any location, width, and height. In the proposed algorithm, a polynomial that approximates the template image is used to match the input image instead of the template image. The proposed algorithm is effective especially when the width and height of the template image differ from the partial image to be matched. An algorithm using the Legendre polynomial is proposed for efficient approximation of the template image. This algorithm not only reduces computational costs, but also improves the quality of the approximated image. It is shown theoretically and experimentally that the computational cost of the proposed algorithm is much smaller than the existing methods.

A matched comparison of perioperative outcomes of a single laparoscopic surgeon versus a multisurgeon robot-assisted cohort for partial nephrectomy.

PubMed

Ellison, Jonathan S; Montgomery, Jeffrey S; Wolf, J Stuart; Hafez, Khaled S; Miller, David C; Weizer, Alon Z

2012-07-01

Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared. All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications. Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively). Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Commentary on "a matched comparison of perioperative outcomes of a single laparoscopic surgeon versus a multisurgeon robot-assisted cohort for partial nephrectomy." Ellison JS, Montgomery JS, Wolf Jr JS, Hafez KS, Miller DC, Weizer AZ, Department of Urology, University of Michigan, Ann Arbor, MI, USA: J Urol 2012;188(1):45-50.

PubMed

Kane, Christopher

2013-02-01

Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared. All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications. Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively). Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

PubMed Central

Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

2016-01-01

Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive care, leflunomide may be a feasible option without significant toxicity. PMID:27094950

[Two Kinds of HLA-mismatched Allogeneic Hematopoictic Stem Cell Transplantation for Treatment of Hematologic Malignancies].

PubMed

Li, Wei-Da; Gao, Zhi-Yong; Yu, Xin-Jian; Lu, Da-Yu; Lu, Dao-Pei

2016-04-01

To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance. A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used. All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%). These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

Do Stem Taper Microgrooves Influence Taper Corrosion in Total Hip Arthroplasty? A Matched Cohort Retrieval Study

PubMed Central

Arnholt, Christina M.; MacDonald, Daniel W.; Underwood, Richard; Guyer, Eric P.; Rimnac, Clare M.; Kurtz, Steven M.; Mont, Michael A.; Klein, Gregg; Lee, Gwo-Chin; Chen, Antonia F.; Hamlin, Brian; Cates, Harold; Malkani, Arthur; Kraay, Matthew

2017-01-01

Background Previous studies identified imprinting of the stem morphology onto the interior head bore, leading researchers to hypothesize an influence of taper topography on mechanically assisted crevice corrosion (MACC). The purpose of this study was to analyze whether micro-grooved stem tapers result in greater fretting corrosion damage than smooth stem tapers. Methods A matched cohort of 120 retrieved head-stem pairs from metal-on-polyethylene bearings was created controlling for implantation time, flexural rigidity, apparent length of engagement, and head size. There were two groups of 60 heads each, mated with either smooth or micro-grooved stem tapers. A high precision roundness machine was used to measure and categorize the surface morphology. Fretting corrosion damage at the head/neck junction was characterized using the Higgs-Goldberg scoring method. Fourteen of the most damaged heads, were analyzed for the maximum depth of material loss and focused ion beam (FIB) cross-sectioned to view oxide and base metal. Results Fretting corrosion damage was not different between the two cohorts at the femoral head (p = 0.14, Mann Whitney) or stem tapers (p = 0.35). There was no difference in the maximum depths of material loss between the cohorts (p = 0.71). Cross sectioning revealed contact damage, signs of micro-motion, and chromium rich oxide layers in both cohorts. Micro-groove imprinting did not appear to have a different effect on the fretting corrosion behavior. Conclusion The results of this matched cohort retrieval study do not support the hypothesis that taper surfaces with micro-grooved stems exhibit increased in vivo fretting corrosion damage or material release. PMID:28111124

Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

PubMed Central

Rosselló, Ricardo Antonio; Chen, Chun-Chun; Dai, Rui; Howard, Jason T; Hochgeschwender, Ute; Jarvis, Erich D

2013-01-01

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range. DOI: http://dx.doi.org/10.7554/eLife.00036.001 PMID:24015354

Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor T cells for refractory severe aplastic anaemia.

PubMed

Purev, Enkhtsetseg; Tian, Xin; Aue, Georg; Pantin, Jeremy; Vo, Phuong; Shalabi, Reem; Reger, Robert N; Cook, Lisa; Ramos, Catalina; Cho, Elena; Worthy, Tat'yana; Khuu, Hanh; Stroncek, David; Young, Neal S; Childs, Richard W

2017-03-01

Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34 + selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 10 6 CD34 +  cells/kg and 2 × 10 7 non-mobilized CD3 + T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD. © 2017 John Wiley & Sons Ltd.

Estimation of Tree Position and STEM Diameter Using Simultaneous Localization and Mapping with Data from a Backpack-Mounted Laser Scanner

NASA Astrophysics Data System (ADS)

Holmgren, J.; Tulldahl, H. M.; Nordlöf, J.; Nyström, M.; Olofsson, K.; Rydell, J.; Willén, E.

2017-10-01

A system was developed for automatic estimations of tree positions and stem diameters. The sensor trajectory was first estimated using a positioning system that consists of a low precision inertial measurement unit supported by image matching with data from a stereo-camera. The initial estimation of the sensor trajectory was then calibrated by adjustments of the sensor pose using the laser scanner data. Special features suitable for forest environments were used to solve the correspondence and matching problems. Tree stem diameters were estimated for stem sections using laser data from individual scanner rotations and were then used for calibration of the sensor pose. A segmentation algorithm was used to associate stem sections to individual tree stems. The stem diameter estimates of all stem sections associated to the same tree stem were then combined for estimation of stem diameter at breast height (DBH). The system was validated on four 20 m radius circular plots and manual measured trees were automatically linked to trees detected in laser data. The DBH could be estimated with a RMSE of 19 mm (6 %) and a bias of 8 mm (3 %). The calibrated sensor trajectory and the combined use of circle fits from individual scanner rotations made it possible to obtain reliable DBH estimates also with a low precision positioning system.

Proximate nutritional composition of CELSS crops grown at different CO2 partial pressures

NASA Technical Reports Server (NTRS)

Wheeler, R. M.; Mackowiak, C. L.; Sager, J. C.; Knott, W. M.; Berry, W. L.

1994-01-01

Two Controlled Ecological Life Support System (CELSS) candidate crops, soybean (Glycine max) and potato (Solanum tuberosum), were grown hydroponically in controlled environments maintained at carbon dioxide (CO2) partial pressures ranging from 0.05 to 1.00 kPa (500 to 10,000 ppm at 101 kPa atmospheric pressure). Plants were harvested at maturity (90 days for soybean and 105 days for potato) and all tissues analyzed for proximate nutritional composition (i.e. protein, fat, carbohydrate, crude fiber, and ash content). Soybean seed ash and crude fiber were higher and carbohydrate was lower than values reported for field-grown seed. Potato tubers showed little difference from field-grown tubers. Crude fiber of soybean stems and leaves increased with increased CO2, as did soybean leaf protein (total nitrogen). Potato leaf and stem (combined) protein levels also increased with increased CO2, while leaf and stem carbohydrates decreased. Values for leaf and stem protein and ash were higher than values generally reported for field-grown plants for both species. Results suggest that CO2 partial pressure should have little influence on proximate composition of potato tubers or soybean seed, but that high ash and protein levels might be expected from leaves and stems of crops grown in controlled environments of a CELSS.

Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.

PubMed

van Gelder, Michel; Ziagkos, Dimitris; de Wreede, Liesbeth; van Biezen, Anja; Dreger, Peter; Gramatzki, Martin; Stelljes, Matthias; Andersen, Niels Smedegaard; Schaap, Nicolaas; Vitek, Antonin; Beelen, Dietrich; Lindström, Vesa; Finke, Jürgen; Passweg, Jacob; Eder, Matthias; Machaczka, Maciej; Delgado, Julio; Krüger, William; Raida, Luděk; Socié, Gerard; Jindra, Pavel; Afanasyev, Boris; Wagner, Eva; Chalandon, Yves; Henseler, Anja; Schoenland, Stefan; Kröger, Nicolaus; Schetelig, Johannes

2017-10-01

Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted. Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%). Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor. Copyright © 2017 Elsevier Inc. All rights reserved.

A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

DTIC Science & Technology

2016-08-15

HLA ISSN 2059-2302 A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell...from different inter- national donor registries by challenging them with simulated input data and subse- quently comparing the output. This experiment...original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Comparative reference validation of HLA

Cord blood stem cells for hematopoietic stem cell transplantation in the UK: how big should the bank be?

PubMed

Querol, Sergio; Mufti, Ghulam J; Marsh, Steven G E; Pagliuca, Antonio; Little, Ann-Margaret; Shaw, Bronwen E; Jeffery, Robert; Garcia, Joan; Goldman, John M; Madrigal, J Alejandro

2009-04-01

A stored cord blood donation may be a valuable source of hemopoietic stem cells for allogeneic transplantation when a matched sibling donor is not available. We carried out a study to define the optimal size of a national cord blood bank for the UK. We calculated the actual numbers of possible donors and the chance of finding at least one donor for 2,000 unselected and for 722 non-North Western European patients for whom searches had been initiated as a function of three levels of HLA matching (4, 5 and 6 out of 6 alleles by HLA-A, -B low and -DRB1 high resolution HLA typing) according to various donor bank sizes. With a bank size of 50,000, 80% of patients will have at least one donor unit available at the 5 out of 6 HLA allele match level (median 9 donors per patient), and 98% will have at least one donor at the 4 out of 6 allele match level (median 261). Doubling the size of the bank yields at least one donor for only an additional 6% of patients at the 5 of 6 allele match level. Moreover, for non-North Western European patients a 50,000 unit bank provides a donor for 50% at the 5 allele match level, and for 96% at the 4 allele match level. A bank containing 50,000 units is optimal for the UK and larger banks would only marginally increase the chance of finding suitable units.

Whole exome sequencing to estimate alloreactivity potential between donors and recipients in stem cell transplantation

PubMed Central

Sampson, Juliana K.; Sheth, Nihar U.; Koparde, Vishal N.; Scalora, Allison F.; Serrano, Myrna G.; Lee, Vladimir; Roberts, Catherine H.; Jameson-Lee, Max; Ferreira-Gonzalez, Andrea; Manjili, Masoud H.; Buck, Gregory A.; Neale, Michael C.; Toor, Amir A.

2016-01-01

Summary Whole exome sequencing (WES) was performed on stem cell transplant donor-recipient (D-R) pairs to determine the extent of potential antigenic variation at a molecular level. In a small cohort of D-R pairs, a high frequency of sequence variation was observed between the donor and recipient exomes independent of human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in HLA-matched unrelated, compared with related D-R pairs. When mapped to individual chromosomes, these polymorphic nucleotides were uniformly distributed across the entire exome. In conclusion, WES reveals extensive nucleotide sequence variation in the exomes of HLA-matched donors and recipients. PMID:24749631

Optimal Dosing and Dynamic Distribution of Vaccines in an Influenza Pandemic

PubMed Central

McCaw, James; Becker, Niels; Nolan, Terry; MacIntyre, C. Raina

2009-01-01

Limited production capacity and delays inherent in vaccine development are major hurdles to the widespread use of vaccines to mitigate the effects of a new influenza pandemic. Antigen-sparing vaccines have the most potential to increase population coverage but may be less efficacious. The authors explored this trade-off by applying simple models of influenza transmission and dose response to recent clinical trial data. In this paper, these data are used to illustrate an approach to comparing vaccines on the basis of antigen supply and inferred efficacy. The effects of delays in matched vaccine availability and seroconversion on epidemic size during pandemic phase 6 were also studied. The authors infer from trial data that population benefits stem from the use of low-antigen vaccines. Delayed availability of a matched vaccine could be partially alleviated by using a 1-dose vaccination program with increased coverage and reduced time to full protection. Although less immunogenic, an overall attack rate of up to 6% lower than a 2-dose program could be achieved. However, if prevalence at vaccination is above 1%, effectiveness is much reduced, emphasizing the need for other control measures. PMID:19395691

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry.

PubMed

Michallet, M; Sobh, M; Milligan, D; Morisset, S; Niederwieser, D; Koza, V; Ruutu, T; Russell, N H; Verdonck, L; Dhedin, N; Vitek, A; Boogaerts, M; Vindelov, L; Finke, J; Dubois, V; van Biezen, A; Brand, R; de Witte, T; Dreger, P

2010-10-01

We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.

Allogeneic Stem Cell Transplantation: A Historical and Scientific Overview.

PubMed

Singh, Anurag K; McGuirk, Joseph P

2016-11-15

The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity. Preclinical and clinical research in the field has contributed to an advanced understanding of histocompatibility, graft-versus-host disease (GVHD), GVL effect, and immune reconstitution after transplant. Improved donor selection, tailored conditioning regimens, and better supportive care have helped reduce transplant-related morbidity and mortality and expanded access. The development of unrelated donor registries and increased utilization of cord blood and partially matched related donor transplants have ensured a donor for essentially everyone who needs a transplant. However, significant barriers still remain in the form of disease relapse, GVHD infectious complications, and regimen-related toxicities. Recent developments in the field of cellular therapy are expected to further improve the efficacy of transplant. In this review, we discuss the current science of HSCT from a historical perspective, highlighting major discoveries. We also speculate on future directions in this field. Cancer Res; 76(22); 6445-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Validation of a Pediatric Early Warning Score in Hospitalized Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

PubMed

Agulnik, Asya; Forbes, Peter W; Stenquist, Nicole; Rodriguez-Galindo, Carlos; Kleinman, Monica

2016-04-01

To evaluate the correlation of a Pediatric Early Warning Score with unplanned transfer to the PICU in hospitalized oncology and hematopoietic stem cell transplant patients. We performed a retrospective matched case-control study, comparing the highest documented Pediatric Early Warning Score within 24 hours prior to unplanned PICU transfers in hospitalized pediatric oncology and hematopoietic stem cell transplant patients between September 2011 and December 2013. Controls were patients who remained on the inpatient unit and were matched 2:1 using age, condition (oncology vs hematopoietic stem cell transplant), and length of hospital stay. Pediatric Early Warning Scores were documented by nursing staff at least every 4 hours as part of routine care. Need for transfer was determined by a PICU physician called to evaluate the patient. A large tertiary/quaternary free-standing academic children's hospital. One hundred ten hospitalized pediatric oncology patients (42 oncology, 68 hematopoietic stem cell transplant) requiring unplanned PICU transfer and 220 matched controls. None. Using the highest score in the 24 hours prior to transfer for cases and a matched time period for controls, the Pediatric Early Warning Score was highly correlated with the need for PICU transfer overall (area under the receiver operating characteristic = 0.96), and in the oncology and hematopoietic stem cell transplant groups individually (area under the receiver operating characteristic = 0.95 and 0.96, respectively). The difference in Pediatric Early Warning Score results between the cases and controls was noted as early as 24 hours prior to PICU admission. Seventeen patients died (15.4%). Patients with higher Pediatric Early Warning Scores prior to transfer had increased PICU mortality (p = 0.028) and length of stay (p = 0.004). We demonstrate that our institution's Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and hematopoietic stem cell transplant patients. Furthermore, we found an association between higher scores and PICU mortality. This is the first validation of a Pediatric Early Warning Score specific to the pediatric oncology and hematopoietic stem cell transplant populations, and supports the use of Pediatric Early Warning Scores as a method of early identification of clinical deterioration in this high-risk population.

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

PubMed

Kindwall-Keller, Tamila L; Ballen, Karen K

2017-09-01

Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic stem cell transplant will have a donor. © AlphaMed Press 2017.

Matching games with partial information

NASA Astrophysics Data System (ADS)

Laureti, Paolo; Zhang, Yi-Cheng

2003-06-01

We analyze different ways of pairing agents in a bipartite matching problem, with regard to its scaling properties and to the distribution of individual “satisfactions”. Then we explore the role of partial information and bounded rationality in a generalized Marriage Problem, comparing the benefits obtained by self-searching and by a matchmaker. Finally we propose a modified matching game intended to mimic the way consumers’ information makes firms to enhance the quality of their products in a competitive market.

Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

PubMed Central

Campbell, F; Williams, G T; Appleton, M A; Dixon, M F; Harris, M; Williams, E D

1996-01-01

BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems. PMID:8944567

Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO(®)) histological and immunohistochemical study.

PubMed

El-Hadidy, M R; El-Hadidy, A R; Bhaa, A; Asker, S A; Mazroa, S A

2014-04-01

Moist Exposed Burn Ointment (MEBO(®)) is widely used topical agent applied on skin burn. This study investigated the effect of MEBO topical application on activation and proliferation of epidermal stem cells through the immunohistochemical localization of cytokeratin 19 (CK19) as a known marker expressed in epidermal stem cells. Biopsies from normal skin and burn wounds were taken from 21 patients with partial thickness burn 1, 4, 7, 14, 21, and 28 days after treatment with MEBO. Tissue sections were prepared for histological study and for CK19 immunohistochemical localization. In control skin, only few cells showed a positive CK19 immune-reaction. Burned skin showed necrosis of full thickness epidermis that extended to dermis. Gradual regeneration of skin accompanied with an enhancement in CK19 immune-reactivity was noted 4, 7, 14 and 21 days after treatment with MEBO. On day 28, a complete regeneration of skin was observed with a return of CK19 immune-reactivity to the basal pattern again. In conclusion, the enhancement of epidermal stem cell marker CK19 after treatment of partial thickness burn injuries with MEBO suggested the role of MEBO in promoting epidermal stem cell activation and proliferation during burn wound healing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0522 TITLE: Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0522 5c...bioprinting process using stem cells for retinal tissue regeneration. The LBL nature of the bioprinting process matches nicely with the native

STEM VQ Method, Using Scanning Transmission Electron Microscopy (STEM) for Accurate Virus Quantification

DTIC Science & Technology

2017-02-02

Corresponding Author Abstract Accurate virus quantification is sought, but a perfect method still eludes the scientific community. Electron...unlimited. UNCLASSIFIED 2 provides morphology data and counts all viral particles, including partial or noninfectious particles; however, EM methods ...consistent, reproducible virus quantification method called Scanning Transmission Electron Microscopy – Virus Quantification (STEM-VQ) which simplifies

Whole exome sequencing to estimate alloreactivity potential between donors and recipients in stem cell transplantation.

PubMed

Sampson, Juliana K; Sheth, Nihar U; Koparde, Vishal N; Scalora, Allison F; Serrano, Myrna G; Lee, Vladimir; Roberts, Catherine H; Jameson-Lee, Max; Ferreira-Gonzalez, Andrea; Manjili, Masoud H; Buck, Gregory A; Neale, Michael C; Toor, Amir A

2014-08-01

Whole exome sequencing (WES) was performed on stem cell transplant donor-recipient (D-R) pairs to determine the extent of potential antigenic variation at a molecular level. In a small cohort of D-R pairs, a high frequency of sequence variation was observed between the donor and recipient exomes independent of human leucocyte antigen (HLA) matching. Nonsynonymous, nonconservative single nucleotide polymorphisms were approximately twice as frequent in HLA-matched unrelated, compared with related D-R pairs. When mapped to individual chromosomes, these polymorphic nucleotides were uniformly distributed across the entire exome. In conclusion, WES reveals extensive nucleotide sequence variation in the exomes of HLA-matched donors and recipients. © 2014 John Wiley & Sons Ltd.

Assessment of a model of forest dynamics under contrasting climate and disturbance regimes in the Pacific Northwest [FORCLIM

USGS Publications Warehouse

Busing, Richard T.; Solomon, Allen M.

2005-01-01

An individual-based model of forest dynamics (FORCLIM) was tested for its ability to simulate forest composition and structure in the Pacific Northwest region of North America. Simulation results across gradients of climate and disturbance were compared to forest survey data from several vegetation zones in western Oregon. Modelled patterns of tree species composition, total basal area and stand height across climate gradients matched those in the forest survey data. However, the density of small stems (<50 cm DBH) was underestimated by the model. Thus actual size-class structure and other density-based parameters of stand structure were not simulated with high accuracy. The addition of partial-stand disturbances at moderate frequencies (<0.01 yr-1) often improved agreement between simulated and actual results. Strengths and weaknesses of the FORCLIM model in simulating forest dynamics and structure in the Pacific Northwest are discussed.

Bin Ratio-Based Histogram Distances and Their Application to Image Classification.

PubMed

Hu, Weiming; Xie, Nianhua; Hu, Ruiguang; Ling, Haibin; Chen, Qiang; Yan, Shuicheng; Maybank, Stephen

2014-12-01

Large variations in image background may cause partial matching and normalization problems for histogram-based representations, i.e., the histograms of the same category may have bins which are significantly different, and normalization may produce large changes in the differences between corresponding bins. In this paper, we deal with this problem by using the ratios between bin values of histograms, rather than bin values' differences which are used in the traditional histogram distances. We propose a bin ratio-based histogram distance (BRD), which is an intra-cross-bin distance, in contrast with previous bin-to-bin distances and cross-bin distances. The BRD is robust to partial matching and histogram normalization, and captures correlations between bins with only a linear computational complexity. We combine the BRD with the ℓ1 histogram distance and the χ(2) histogram distance to generate the ℓ1 BRD and the χ(2) BRD, respectively. These combinations exploit and benefit from the robustness of the BRD under partial matching and the robustness of the ℓ1 and χ(2) distances to small noise. We propose a method for assessing the robustness of histogram distances to partial matching. The BRDs and logistic regression-based histogram fusion are applied to image classification. The experimental results on synthetic data sets show the robustness of the BRDs to partial matching, and the experiments on seven benchmark data sets demonstrate promising results of the BRDs for image classification.

Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study.

PubMed

Vangsness, C Thomas; Farr, Jack; Boyd, Joel; Dellaero, David T; Mills, C Randal; LeRoux-Williams, Michelle

2014-01-15

There are limited treatment options for tissue restoration and the prevention of degenerative changes in the knee. Stem cells have been a focus of intense preclinical research into tissue regeneration but limited clinical investigation. In a randomized, double-blind, controlled study, the safety of the intra-articular injection of human mesenchymal stem cells into the knee, the ability of mesenchymal stem cells to promote meniscus regeneration following partial meniscectomy, and the effects of mesenchymal stem cells on osteoarthritic changes in the knee were investigated. A total of fifty-five patients at seven institutions underwent a partial medial meniscectomy. A single superolateral knee injection was given within seven to ten days after the meniscectomy. Patients were randomized to one of three treatment groups: Group A, in which patients received an injection of 50 × 10⁶ allogeneic mesenchymal stem cells; Group B, 150 × 10⁶ allogeneic mesenchymal stem cells; and the control group, a sodium hyaluronate (hyaluronic acid/hyaluronan) vehicle control. Patients were followed to evaluate safety, meniscus regeneration, the overall condition of the knee joint, and clinical outcomes at intervals through two years. Evaluations included sequential magnetic resonance imaging (MRI). No ectopic tissue formation or clinically important safety issues were identified. There was significantly increased meniscal volume (defined a priori as a 15% threshold) determined by quantitative MRI in 24% of patients in Group A and 6% in Group B at twelve months post meniscectomy (p = 0.022). No patients in the control group met the 15% threshold for increased meniscal volume. Patients with osteoarthritic changes who received mesenchymal stem cells experienced a significant reduction in pain compared with those who received the control, on the basis of visual analog scale assessments. There was evidence of meniscus regeneration and improvement in knee pain following treatment with allogeneic human mesenchymal stem cells. These results support the study of human mesenchymal stem cells for the apparent knee-tissue regeneration and protective effects.

Extensible Adaptive System for STEM Learning

DTIC Science & Technology

2013-07-16

Copyright 2013 Raytheon BBN Technologies Corp. All Rights Reserved ONR STEM Grand Challenge Extensible Adaptive System for STEM Learning ...Contract # N00014-12-C-0535 Raytheon BBN Technologies Corp. (BBN) Reference # 14217 In partial fulfillment of contract deliverable item # A001...Quarterly Progress Report #2 April 7, 2013 –July 6, 2013 Submitted July 16, 2013 BBN Technical POC: John Makhoul Raytheon BBN Technologies

Identification of Ccr4-Not Complex Components as Regulators of Transition from Partial to Genuine Induced Pluripotent Stem Cells

PubMed Central

Kamon, Masayoshi; Katano, Miyuki; Hiraki-Kamon, Keiko; Hishida, Tomoaki; Nakachi, Yutaka; Mizuno, Yosuke; Okazaki, Yasushi; Suzuki, Ayumu; Hirasaki, Masataka; Ueda, Atsushi; Nishimoto, Masazumi; Kato, Hidemasa

2014-01-01

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by defined factors. However, substantial cell numbers subjected to iPSC induction stray from the main reprogramming route and are immortalized as partial iPSCs. These partial iPSCs can become genuine iPSCs by exposure to the ground state condition. However, such conversion is only possible for mouse partial iPSCs, and it is not applicable to human cells. Moreover, the molecular basis of this conversion is completely unknown. Therefore, we performed genome-wide screening with a piggyBac vector to identify genes involved in conversion from partial to genuine iPSCs. This screening led to identification of Cnot2, one of the core components of the Ccr4-Not complex. Subsequent analyses revealed that other core components, Cnot1 and Cnot3, also contributed to the conversion. Thus, our data have uncovered a novel role of core components of the Ccr4-Not complex as regulators of transition from partial to genuine iPSCs. PMID:24200330

Charting improvements in US registry HLA typing ambiguity using a typing resolution score.

PubMed

Paunić, Vanja; Gragert, Loren; Schneider, Joel; Müller, Carlheinz; Maiers, Martin

2016-07-01

Unrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score (TRS), based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations. We apply the TRS to chart improvement in HLA typing within the Be The Match Registry of the United States from the initiation of DNA-based HLA typing to the current state of high-resolution typing using next-generation sequencing technologies. In addition, we present a publicly available online tool for evaluation of any given HLA typing. This TRS objectively evaluates HLA typing methods and can help define standards for acceptable recruitment HLA typing. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Six years' experience of tolerance induction in renal transplantation using stem cell therapy.

PubMed

Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

2018-02-01

Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We report results of TI protocol (TIP) using stem cell therapy (SCT) included adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non-myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti-thymoglobulin and Rituximab, without using conventional immunosuppression. Transplantation was performed following acceptable lymphocyte cross-match, flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). Monitoring included serum creatinine (SCr), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100days and yearly in willing patients. Rescue immunosuppression was planned for rejection/DSA/positive MLR. Over mean 6±0.37year follow-up patient survival was 80% and death-censored graft survival was 90%. Mean SCr was 1.44±0.41mg/dL. This is the first clinical report of sustained TI in LDRT for 6years using SCT. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone preserving level of osteotomy in short-stem total hip arthroplasty does not influence stress shielding dimensions - a comparing finite elements analysis.

PubMed

Burchard, Rene; Braas, Sabrina; Soost, Christian; Graw, Jan Adriaan; Schmitt, Jan

2017-08-07

The main objective of every new development in total hip arthroplasty (THA) is the longest possible survival of the implant. Periprosthetic stress shielding is a scientifically proven phenomenon which leads to inadvertent bone loss. So far, many studies have analysed whether implanting different hip stem prostheses result in significant preservation of bone stock. The aim of this preclinical study was to investigate design-depended differences of the stress shielding effect after implantation of a selection of short-stem THA-prostheses that are currently available. Based on computerised tomography (CT), a finite elements (FE) model was generated and a virtual THA was performed with different stem designs of the implant. Stems were chosen by osteotomy level at the femoral neck (collum, partial collum, trochanter sparing, trochanter harming). Analyses were performed with previously validated FE models to identify changes in the strain energy density (SED). In the trochanteric region, only the collum-type stem demonstrated a biomechanical behaviour similar to the native femur. In contrast, no difference in biomechanical behaviour was found between partial collum, trochanter harming and trochanter sparing models. All of the short stem-prostheses showed lower stress-shielding than a standard stem. Based on the results of this study, we cannot confirm that the design of current short stem THA-implants leads to a different stress shielding effect with regard to the level of osteotomy. Somehow unexpected, we found a bone stock protection in metadiaphyseal bone by simulating a more distal approach for osteotomy. Further clinical and biomechanical research including long-term results is needed to understand the influence of short-stem THA on bone remodelling and to find the optimal stem-design for a reduction of the stress shielding effect.

Correlation-coefficient-based fast template matching through partial elimination.

PubMed

Mahmood, Arif; Khan, Sohaib

2012-04-01

Partial computation elimination techniques are often used for fast template matching. At a particular search location, computations are prematurely terminated as soon as it is found that this location cannot compete with an already known best match location. Due to the nonmonotonic growth pattern of the correlation-based similarity measures, partial computation elimination techniques have been traditionally considered inapplicable to speed up these measures. In this paper, we show that partial elimination techniques may be applied to a correlation coefficient by using a monotonic formulation, and we propose basic-mode and extended-mode partial correlation elimination algorithms for fast template matching. The basic-mode algorithm is more efficient on small template sizes, whereas the extended mode is faster on medium and larger templates. We also propose a strategy to decide which algorithm to use for a given data set. To achieve a high speedup, elimination algorithms require an initial guess of the peak correlation value. We propose two initialization schemes including a coarse-to-fine scheme for larger templates and a two-stage technique for small- and medium-sized templates. Our proposed algorithms are exact, i.e., having exhaustive equivalent accuracy, and are compared with the existing fast techniques using real image data sets on a wide variety of template sizes. While the actual speedups are data dependent, in most cases, our proposed algorithms have been found to be significantly faster than the other algorithms.

Practical method for appearance match between soft copy and hard copy

NASA Astrophysics Data System (ADS)

Katoh, Naoya

1994-04-01

CRT monitors are often used as a soft proofing device for the hard copy image output. However, what the user sees on the monitor does not match its output, even if the monitor and the output device are calibrated with CIE/XYZ or CIE/Lab. This is especially obvious when correlated color temperature (CCT) of CRT monitor's white point significantly differs from ambient light. In a typical office environment, one uses a computer graphic monitor having a CCT of 9300K in a room of white fluorescent light of 4150K CCT. In such a case, human visual system is partially adapted to the CRT monitor's white point and partially to the ambient light. The visual experiments were performed on the effect of the ambient lighting. Practical method for soft copy color reproduction that matches the hard copy image in appearance is presented in this paper. This method is fundamentally based on a simple von Kries' adaptation model and takes into account the human visual system's partial adaptation and contrast matching.

Robust Point Set Matching for Partial Face Recognition.

PubMed

Weng, Renliang; Lu, Jiwen; Tan, Yap-Peng

2016-03-01

Over the past three decades, a number of face recognition methods have been proposed in computer vision, and most of them use holistic face images for person identification. In many real-world scenarios especially some unconstrained environments, human faces might be occluded by other objects, and it is difficult to obtain fully holistic face images for recognition. To address this, we propose a new partial face recognition approach to recognize persons of interest from their partial faces. Given a pair of gallery image and probe face patch, we first detect keypoints and extract their local textural features. Then, we propose a robust point set matching method to discriminatively match these two extracted local feature sets, where both the textural information and geometrical information of local features are explicitly used for matching simultaneously. Finally, the similarity of two faces is converted as the distance between these two aligned feature sets. Experimental results on four public face data sets show the effectiveness of the proposed approach.

Can mammalian cloning combined with embryonic stem cell technologies be used to treat human diseases?

PubMed Central

Hadjantonakis, Anna-Katerina; Papaioannou, Virginia E

2002-01-01

Cloning is commonly perceived as a means of generating genetically identical individuals, but it can also be used to obtain genetically matched embryo-derived stem cells, which could potentially be used in the treatment of patients. A recent report offers the first 'proof of principle' of such cloning for therapeutic purposes, referred to as nuclear transplantation to produce stem cells for autologous transplantation. PMID:12186652

Pipette-based Method to Study Embryoid Body Formation Derived from Mouse and Human Pluripotent Stem Cells Partially Recapitulating Early Embryonic Development Under Simulated Microgravity Conditions

NASA Astrophysics Data System (ADS)

Shinde, Vaibhav; Brungs, Sonja; Hescheler, Jürgen; Hemmersbach, Ruth; Sachinidis, Agapios

2016-06-01

The in vitro differentiation of pluripotent stem cells partially recapitulates early in vivo embryonic development. More recently, embryonic development under the influence of microgravity has become a primary focus of space life sciences. In order to integrate the technique of pluripotent stem cell differentiation with simulated microgravity approaches, the 2-D clinostat compatible pipette-based method was experimentally investigated and adapted for investigating stem cell differentiation processes under simulated microgravity conditions. In order to keep residual accelerations as low as possible during clinorotation, while also guaranteeing enough material for further analysis, stem cells were exposed in 1-mL pipettes with a diameter of 3.5 mm. The differentiation of mouse and human pluripotent stem cells inside the pipettes resulted in the formation of embryoid bodies at normal gravity (1 g) after 24 h and 3 days. Differentiation of the mouse pluripotent stem cells on a 2-D pipette-clinostat for 3 days also resulted in the formation of embryoid bodies. Interestingly, the expression of myosin heavy chain was downregulated when cultivation was continued for an additional 7 days at normal gravity. This paper describes the techniques for culturing and differentiation of pluripotent stem cells and exposure to simulated microgravity during culturing or differentiation on a 2-D pipette clinostat. The implementation of these methodologies along with -omics technologies will contribute to understand the mechanisms regulating how microgravity influences early embryonic development.

Stress and transcriptional regulation of tick ferritin HC.

PubMed

Mulenga, A; Simser, J A; Macaluso, K R; Azad, A F

2004-08-01

We previously identified a partial Dermacentor variabilis cDNA encoding ferritin HC (HC) subunit homolog (DVFER) that was differentially upregulated in Rickettsia montanensis infected ticks (Mulenga et al., 2003a). We have used rapid amplification of cDNA ends to clone full-length DVFER cDNA and its apparent ortholog from the wood tick, D. andersoni (DAFER), both of which show high sequence similarity to vertebrate than insect ferritin. Both DVFER and DAFER contain the stem-loop structure of a putative iron responsive element in the 5' untranslated region (nucleotide positions, 16-42) and the feroxidase centre loop typical for vertebrate ferritin HC subunits. Quantitative Western and Northern blotting analyses of protein and RNA from unfed and partially fed whole tick as well as dissected tick tissues demonstrated that DVFER is constitutively and ubiquitously expressed. Based on densitometric analysis of detected protein and mRNA bands, DVFER is predominantly expressed in the midgut, and to a lesser extent in the salivary glands, ovary and fatbody. Sham treatment (mechanical injury) and Escherichia coli challenge of D. variabilis ticks stimulated statistically significant (approximately 1.5- and approximately 3.0-fold, respectively) increases in DVFER mRNA abundance over time point matched naive control ticks. These data suggest that DVFER mRNA is nonspecifically up regulated in response to mechanical injury or bacterial infection induced stress.

Robot-assisted laparoscopic versus open partial nephrectomy in patients with chronic kidney disease: A propensity score-matched comparative analysis of surgical outcomes.

PubMed

Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Yoshida, Kazuhiko; Tanabe, Kazunari

2017-07-01

To compare surgical outcomes between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy in patients with chronic kidney disease. Of 550 patients who underwent partial nephrectomy between 2012 and 2015, 163 patients with T1-2 renal tumors who had an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m 2 , and underwent robot-assisted laparoscopic partial nephrectomy or open partial nephrectomy were retrospectively analyzed. To minimize selection bias between the two surgical methods, patient variables were adjusted by 1:1 propensity score matching. The present study included 75 patients undergoing robot-assisted laparoscopic partial nephrectomy and 88 undergoing open partial nephrectomy. After propensity score matching, 40 patients were included in each operative group. The mean preoperative estimated glomerular filtration rate was 49 mL/min/1.73 m 2 . The mean ischemia time was 21 min in robot-assisted laparoscopic partial nephrectomy (warm ischemia) and 35 min in open partial nephrectomy (cold ischemia). Preservation of the estimated glomerular filtration rate 3-6 months postoperatively was not significantly different between robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy (92% vs 91%, P = 0.9348). Estimated blood loss was significantly lower in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group (104 vs 185 mL, P = 0.0025). The postoperative length of hospital stay was shorter in the robot-assisted laparoscopic partial nephrectomy group than in the open partial nephrectomy group (P < 0.0001). The prevalence of Clavien-Dindo grade 3 complications and a negative surgical margin status were not significantly different between the two groups. In our experience, robot-assisted laparoscopic partial nephrectomy and open partial nephrectomy provide similar outcomes in terms of functional preservation and perioperative complications among patients with chronic kidney disease. However, a lower estimated blood loss and shorter postoperative length of hospital stay can be obtained with robot-assisted laparoscopic partial nephrectomy. © 2017 The Japanese Urological Association.

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

PubMed

Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

2017-10-01

Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Experimental Studies on Wave Interactions of Partially Perforated Wall under Obliquely Incident Waves

PubMed Central

Lee, Jong-In; Kim, Young-Taek; Shin, Sungwon

2014-01-01

This study presents wave height distribution in terms of stem wave evolution phenomena on partially perforated wall structures through three-dimensional laboratory experiments. The plain and partially perforated walls were tested to understand their effects on the stem wave evolution under the monochromatic and random wave cases with the various wave conditions, incident angle (from 10 to 40 degrees), and configurations of front and side walls. The partially perforated wall reduced the relative wave heights more effectively compared to the plain wall structure. Partially perforated walls with side walls showed a better performance in terms of wave height reduction compared to the structure without the side wall. Moreover, the relative wave heights along the wall were relatively small when the relative chamber width is large, within the range of the chamber width in this study. The wave spectra showed a frequency dependency of the wave energy dissipation. In most cases, the existence of side wall is a more important factor than the porosity of the front wall in terms of the wave height reduction even if the partially perforated wall was still effective compared to the plain wall. PMID:25254260

Experimental studies on wave interactions of partially perforated wall under obliquely incident waves.

PubMed

Lee, Jong-In; Kim, Young-Taek; Shin, Sungwon

2014-01-01

This study presents wave height distribution in terms of stem wave evolution phenomena on partially perforated wall structures through three-dimensional laboratory experiments. The plain and partially perforated walls were tested to understand their effects on the stem wave evolution under the monochromatic and random wave cases with the various wave conditions, incident angle (from 10 to 40 degrees), and configurations of front and side walls. The partially perforated wall reduced the relative wave heights more effectively compared to the plain wall structure. Partially perforated walls with side walls showed a better performance in terms of wave height reduction compared to the structure without the side wall. Moreover, the relative wave heights along the wall were relatively small when the relative chamber width is large, within the range of the chamber width in this study. The wave spectra showed a frequency dependency of the wave energy dissipation. In most cases, the existence of side wall is a more important factor than the porosity of the front wall in terms of the wave height reduction even if the partially perforated wall was still effective compared to the plain wall.

Hispanic students' mathematics achievement in the context of their high school types as STEM and non-STEM schools

NASA Astrophysics Data System (ADS)

Bicer, Ali; Capraro, Robert M.; Capraro, Mary M.

2018-07-01

The purpose of this paper is to demonstrate Hispanic students' mathematics achievement growth rate in Inclusive science, technology, engineering, and mathematics (STEM) high schools compared to Hispanic students' mathematics achievement growth rate in traditional public schools. Twenty-eight schools, 14 of which were Texas STEM (T-STEM) academies and 14 of which were matched non-STEM schools, were included in this study. A hierarchical linear modelling method was conducted. The result of the present study revealed that there was no difference in Hispanic students' mathematics achievement growth rate in T-STEM academies compared to Hispanic students' mathematics achievement growth rate in comparison schools. However, in terms of gender, the results indicated that female Hispanic students in T-STEM academies outperformed female Hispanic students in comparison schools in their mathematics growth rate.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

PubMed

Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

2017-12-01

Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

Simulation shows that HLA-matched stem cell donors can remain unidentified in donor searches

PubMed Central

Sauter, Jürgen; Solloch, Ute V.; Giani, Anette S.; Hofmann, Jan A.; Schmidt, Alexander H.

2016-01-01

The heterogeneous nature of HLA information in real-life stem cell donor registries may hamper unrelated donor searches. It is even possible that fully HLA-matched donors with incomplete HLA information are not identified. In our simulation study, we estimated the probability of these unnecessarily failed donor searches. For that purpose, we carried out donor searches in several virtual donor registries. The registries differed by size, composition with respect to HLA typing levels, and genetic diversity. When up to three virtual HLA typing requests were allowed within donor searches, the share of unnecessarily failed donor searches ranged from 1.19% to 4.13%, thus indicating that non-identification of completely HLA-matched stem cell donors is a problem of practical relevance. The following donor registry characteristics were positively correlated with the share of unnecessarily failed donor searches: large registry size, high genetic diversity, and, most strongly correlated, large fraction of registered donors with incomplete HLA typing. Increasing the number of virtual HLA typing requests within donor searches up to ten had a smaller effect. It follows that the problem of donor non-identification can be substantially reduced by complete high-resolution HLA typing of potential donors. PMID:26876789

Simulation shows that HLA-matched stem cell donors can remain unidentified in donor searches

NASA Astrophysics Data System (ADS)

Sauter, Jürgen; Solloch, Ute V.; Giani, Anette S.; Hofmann, Jan A.; Schmidt, Alexander H.

2016-02-01

The heterogeneous nature of HLA information in real-life stem cell donor registries may hamper unrelated donor searches. It is even possible that fully HLA-matched donors with incomplete HLA information are not identified. In our simulation study, we estimated the probability of these unnecessarily failed donor searches. For that purpose, we carried out donor searches in several virtual donor registries. The registries differed by size, composition with respect to HLA typing levels, and genetic diversity. When up to three virtual HLA typing requests were allowed within donor searches, the share of unnecessarily failed donor searches ranged from 1.19% to 4.13%, thus indicating that non-identification of completely HLA-matched stem cell donors is a problem of practical relevance. The following donor registry characteristics were positively correlated with the share of unnecessarily failed donor searches: large registry size, high genetic diversity, and, most strongly correlated, large fraction of registered donors with incomplete HLA typing. Increasing the number of virtual HLA typing requests within donor searches up to ten had a smaller effect. It follows that the problem of donor non-identification can be substantially reduced by complete high-resolution HLA typing of potential donors.

A Randomized Trial of a Science, Technology, Engineering, and Mathematics Mentoring Program

ERIC Educational Resources Information Center

Sowers, Jo-Ann; Powers, Laurie; Schmidt, Jessica; Keller, Thomas E.; Turner, Alison; Salazar, Amy; Swank, Paul R.

2017-01-01

Individuals with disabilities are underrepresented in science, technology, engineering, and math (STEM) fields. The purpose of this study was to experimentally evaluate the impact of a STEM mentor intervention and differences between students matched with mentors with or without disabilities on career planning outcomes. An independent groups ×…

Column-by-column observation of dislocation motion in CdTe: Dynamic scanning transmission electron microscopy

NASA Astrophysics Data System (ADS)

Li, Chen; Zhang, Yu-Yang; Pennycook, Timothy J.; Wu, Yelong; Lupini, Andrew R.; Paudel, Naba; Pantelides, Sokrates T.; Yan, Yanfa; Pennycook, Stephen J.

2016-10-01

The dynamics of partial dislocations in CdTe have been observed at the atomic scale using aberration-corrected scanning transmission electron microscopy (STEM), allowing the mobility of different dislocations to be directly compared: Cd-core Shockley partial dislocations are more mobile than Te-core partials, and dislocation cores with unpaired columns have higher mobility than those without unpaired columns. The dynamic imaging also provides insight into the process by which the dislocations glide. Dislocations with dangling bonds on unpaired columns are found to be more mobile because the dangling bonds mediate the bond exchanges required for the dislocations to move. Furthermore, a screw dislocation has been resolved to dissociate into a Shockley partial-dislocation pair along two different directions, revealing a way for the screw dislocation to glide in the material. The results show that dynamic STEM imaging has the potential to uncover the details of dislocation motion not easily accessible by other means.

Ethnic variation in gender-STEM stereotypes and STEM participation: an intersectional approach.

PubMed

O'Brien, Laurie T; Blodorn, Alison; Adams, Glenn; Garcia, Donna M; Hammer, Elliott

2015-04-01

Stereotypes associating men and masculine traits with science, technology, engineering, and mathematics (STEM) fields are ubiquitous, but the relative strength of these stereotypes varies considerably across cultures. The present research applies an intersectional approach to understanding ethnic variation in gender-STEM stereotypes and STEM participation within an American university context. African American college women participated in STEM majors at higher rates than European American college women (Study 1, Study 2, and Study 4). Furthermore, African American women had weaker implicit gender-STEM stereotypes than European American women (Studies 2-4), and ethnic differences in implicit gender-STEM stereotypes partially mediated ethnic differences in STEM participation (Study 2 and Study 4). Although African American men had weaker implicit gender-STEM stereotypes than European American men (Study 4), ethnic differences between men in STEM participation were generally small (Study 1) or nonsignificant (Study 4). We discuss the implications of an intersectional approach for understanding the relationship between gender and STEM participation. (c) 2015 APA, all rights reserved).

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: a multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

PubMed

Detrait, M Y; Morisset, S; Peffault de Latour, R; Yakoub-Agha, I; Crocchiolo, R; Tabrizi, R; Bay, J-O; Chevalier, P; Barraco, F; Raus, N; Vigouroux, S; Magro, L; Mohty, M; Milpied, N; Blaise, D; Socié, G; Michallet, M

2015-02-01

Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6-19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P=0.0021), in patients with a one mismatched donor (P=0.041) and in patients who had received ATG in the conditioning regimen (P=0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

The control of attentional target selection in a colour/colour conjunction task.

PubMed

Berggren, Nick; Eimer, Martin

2016-11-01

To investigate the time course of attentional object selection processes in visual search tasks where targets are defined by a combination of features from the same dimension, we measured the N2pc component as an electrophysiological marker of attentional object selection during colour/colour conjunction search. In Experiment 1, participants searched for targets defined by a combination of two colours, while ignoring distractor objects that matched only one of these colours. Reliable N2pc components were triggered by targets and also by partially matching distractors, even when these distractors were accompanied by a target in the same display. The target N2pc was initially equal in size to the sum of the two N2pc components to the two different types of partially matching distractors and became superadditive from approximately 250 ms after search display onset. Experiment 2 demonstrated that the superadditivity of the target N2pc was not due to a selective disengagement of attention from task-irrelevant partially matching distractors. These results indicate that attention was initially deployed separately and in parallel to all target-matching colours, before attentional allocation processes became sensitive to the presence of both matching colours within the same object. They suggest that attention can be controlled simultaneously and independently by multiple features from the same dimension and that feature-guided attentional selection processes operate in parallel for different target-matching objects in the visual field.

[Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].

PubMed

Peng, Li; Li, Fu-Xi; Shao, Wen-Feng; Xiong, Jing-Bo

2013-10-01

To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

About the composition of self-relevance: Conjunctions not features are bound to the self.

PubMed

Schäfer, Sarah; Frings, Christian; Wentura, Dirk

2016-06-01

Sui and colleagues (Journal of Experimental Psychology: Human Perception and Performance, 38, 1105-1117, 2012) introduced a matching paradigm to investigate prioritized processing of instructed self-relevance. They arbitrarily assigned simple geometric shapes to the participant and two other persons. Subsequently, the task was to judge whether label-shape pairings matched or not. The authors found a remarkable self-prioritization effect, that is, for matching self-related trials verification was very fast and accurate in comparison to the non-matching conditions. We analyzed whether single features or feature conjunctions are tagged to the self. In particular, we assigned colored shapes to the labels and included partial-matching trials (i.e., trials in which only one feature matched the label, whereas the other feature did not match the label). If single features are tagged to the self, partial matches would result in interference, whereas they should elicit the same data pattern as non-matching trials if only feature conjunctions are tagged to the self. Our data suggest the latter; only feature conjunctions are tagged to the self and are processed in a prioritized manner. This result emphasizes the functionality of self-relevance as a selection mechanism.

Stem cell transplantation of matched sibling donors compared with immunosuppressive therapy for acquired severe aplastic anaemia: a Cochrane systematic review.

PubMed

Peinemann, Frank; Labeit, Alexander Michael

2014-07-15

Acquired severe aplastic anaemia is a rare and potentially fatal disease. The aim of this Cochrane review was to evaluate the effectiveness and adverse events of first-line allogeneic haematopoietic stem cell transplantation of human leucocyte antigen (HLA)-matched sibling donors compared with first-line immunosuppressive therapy. Specialised stem cell transplantations units in primary care hospitals. We included 302 participants with newly diagnosed acquired severe aplastic anaemia. The age ranged from early childhood to young adulthood. We excluded studies on participants with secondary aplastic anaemia. We included allogeneic haematopoietic stem cell transplantation as the test intervention harvested from any source of matched sibling donor and serving as a first-line therapy. We included immunosuppressive therapy as comparator with either antithymocyte/antilymphocyte globulin or ciclosporin or a combination of the two. PRIMARY AND SECONDARY OUTCOME MEASURES PLANNED AND FINALLY MEASURED: The primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, graft-versus-host disease, no response to immunosuppressive therapy, relapse after initial successful treatment, secondary clonal disease or malignancies, health-related quality of life and performance scores. We identified three prospective non-randomised controlled trials with a study design that was consistent with the principle of 'Mendelian randomisation' in allocating patients to treatment groups. All studies had a high risk of bias due to the study design and were conducted more than 15 years. The pooled HR for overall mortality for the donor group versus the no donor group was 0.95 (95% CI 0.43 to 2.12, p=0.90). There are insufficient and biased data that do not allow any firm conclusions to be made about the comparative effectiveness of first-line allogeneic haematopoietic stem cell transplantation of HLA-matched sibling donors and first-line immunosuppressive therapy of patients with acquired severe aplastic anaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Safety and Tolerability Study of CDX-301 With or Without Plerixafor for Stem Cell Mobilization in Matched Related Allogeneic Donor/Recipient Sibling Transplant Pairs

ClinicalTrials.gov

2017-04-06

For Donors; Related Donors Giving Peripheral Blood Stem Cells (PBSC) to a Sibling; For Recipients; Acute Myelogenous Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS); Chronic Myelogenous Leukemia (CML); Non-Hodgkins Lymphoma (NHL); Hodgkins Disease (HD); Chronic Lymphocytic Leukemia (CLL)

Stem and Derivational-Suffix Processing during Reading by French Second and Third Graders

ERIC Educational Resources Information Center

Cole, Pascale; Bouton, Sophie; Leuwers, Christel; Casalis, Severine; Sprenger-Charolles, Liliane

2012-01-01

Morphological processing by French children was investigated in two experiments. The first showed that second and third graders read pseudowords such as "chat-ure" ("cat-ish") composed of an illegally combined real stem and real derivational suffix faster and more accurately than they read matched pseudowords composed of a pseudostem and a real…

Long-term performance of thermoplastic composite material with cotton burr and stem (CBS) as a partial filler

USDA-ARS?s Scientific Manuscript database

Rationale: Cotton burr and stem (CBS) fraction of cotton gin byproducts has shown promise as a fiber filler in thermoplastic composites, with physical and mechanical properties comparable to that made with wood fiber fillers. However, the long-term performance of this composite material is not known...

Effect of HLA mismatch on acute graft-versus-host disease.

PubMed

Kanda, Junya

2013-09-01

HLA matching between donors and recipients is the most important factor associated with acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

Matched sibling versus matched unrelated allogeneic hematopoietic stem cell transplantation in children with severe acquired aplastic anemia: experience of the polish pediatric group for hematopoietic stem cell transplantation.

PubMed

Szpecht, Dawid; Gorczyńska, Ewa; Kałwak, Krzysztof; Owoc-Lempach, Joanna; Choma, Marta; Styczyński, Jan; Goździk, Jolanta; Dłużniewska, Agnieszka; Wysocki, Mariusz; Kowalczyk, Jerzy R; Chybicka, Alicja; Pieczonka, Anna; Wachowiak, Jacek

2012-06-01

In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

Mismatched HLA-DRB3 Can Induce a Potent Immune Response After HLA 10/10 Matched Stem Cell Transplantation.

PubMed

van Balen, Peter; van Luxemburg-Heijs, Simone A P; van de Meent, Marian; van Bergen, Cornelis A M; Halkes, Constantijn J M; Jedema, Inge; Falkenburg, J H Frederik

2017-12-01

Donors for allogeneic stem cell transplantation are preferentially matched with patients for HLA-A, -B, -C, and -DRB1. Mismatches between donor and patient in these alleles are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with limited relevance, although mismatches in HLA-DQ and HLA-DP can result in alloimmune responses. Mismatches in HLA-DRB3, 4, and 5 are usually not taken into account in donor selection. Conversion of chimerism in the presence of GVHD after CD4 donor lymphocyte infusion was observed in a patient, HLA 10/10 matched, but mismatched for HLA-DRB3 and HLA-DPB1 compared with the donor. Alloreactive CD4 T cells were isolated from peripheral blood after CD4 donor lymphocyte infusion and recognition of donor-derived target cells transduced with the mismatched patient variant HLA-DRB3 and HLA-DPB1 molecule was tested. A dominant polyclonal CD4 T cell response against patient's mismatched HLA-DRB3 molecule was found in addition to an immune response against patient's mismatched HLA-DPB1 molecule. CD4 T cells specific for these HLA class II molecules recognized both hematopoietic target cells as well as GVHD target cells. In contrast to the assumption that mismatches in HLA-DRB3, 4, and 5 are not of immunogenic significance after HLA 10/10 matched allogeneic stem cell transplantation, we show that in this matched setting not only mismatches in HLA-DPB1, but also mismatches in HLA-DRB3 may induce a polyclonal allo-immune response associated with conversion of chimerism and severe GVHD.

Data of continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surfaces

PubMed Central

Yeh, Chin-Chen; Muduli, Saradaprasan; Peng, I-Chia; Lu, Yi-Tung; Ling, Qing-Dong; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Kumar, S. Suresh; Murugan, Kadarkarai; Chen, Da-Chung; Lee, Hsin-chung; Chang, Yung; Higuchi, Akon

2016-01-01

This data article contains two figures and one table supporting the research article entitled: “Continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surface” [1]. The table shows coating conditions of three copolymers, poly(styrene-co-acrylic acid) grafted with oligovitronectin, poly(styrene-co-N-isopropylacrylamide) and poly(styrene-co-polyethylene glycol methacrylate) to prepare thermoresponsive surface. XPS spectra show the nitrogen peak of the polystyrene surface coated with poly(styrene-co-acrylic acid) grafted with oligovitronectin. The surface coating density analyzed from sorption of poly(styrene-co-acrylic acid) grafted with oligovitronectin by UV–vis spectroscopy is also presented. PMID:26909373

Making a Difference in Science Education: The Impact of Undergraduate Research Programs

PubMed Central

Eagan, M. Kevin; Hurtado, Sylvia; Chang, Mitchell J.; Garcia, Gina A.; Herrera, Felisha A.; Garibay, Juan C.

2014-01-01

To increase the numbers of underrepresented racial minority students in science, technology, engineering, and mathematics (STEM), federal and private agencies have allocated significant funding to undergraduate research programs, which have been shown to students’ intentions of enrolling in graduate or professional school. Analyzing a longitudinal sample of 4,152 aspiring STEM majors who completed the 2004 Freshman Survey and 2008 College Senior Survey, this study utilizes multinomial hierarchical generalized linear modeling (HGLM) and propensity score matching techniques to examine how participation in undergraduate research affects STEM students’ intentions to enroll in STEM and non-STEM graduate and professional programs. Findings indicate that participation in an undergraduate research program significantly improved students’ probability of indicating plans to enroll in a STEM graduate program. PMID:25190821

BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: Clinical characteristics and utility of leflunomide treatment.

PubMed

Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

2016-04-18

BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Hemorrhagic cystitis (HC) was observed in 30 patients (43.5%), and among them, 18 patients (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (range, 13-63). Patients received Allo-SCT from acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1).The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97) after transplantation and 22 days (range, 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response (CR), one partial response (PR), and five no response (NR). Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2) and PR (n=2). The median duration from the start of leflunomide therapy to response was 13 days (range, 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity.

Molecular cytogenetic characterization and stem rust resistance of five wheat-thinopyrum ponticum partial amphiploids

USDA-ARS?s Scientific Manuscript database

Partial amphiploids created by crossing common wheat (Triticum aestivum L.) and Thinopyrum ponticum (Podp.), Barkworth & D. R. Dewey may be resistant to major wheat diseases and are an important intermediate material in wheat breeding. In this study, we examined chromosome composition of five Xiaoy...

Effects of Hypoglycemia on Circulating Stem and Progenitor Cells in Diabetic Patients.

PubMed

Fadini, Gian Paolo; Boscari, Federico; Cappellari, Roberta; Galasso, Silvia; Rigato, Mauro; Bonora, Benedetta Maria; D'Anna, Marianna; Bruttomesso, Daniela; Avogaro, Angelo

2018-03-01

Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2). Tertiary referral inpatient clinic. Type 1 diabetic patients (Study 1, n = 19); diabetic patients hospitalized for severe iatrogenic hypoglycemia, matched inpatient and outpatient controls (Study 2, n = 22/group). Type 1 diabetic patients underwent two in-hospital sessions of glucose monitoring during a breakfast meal with or without induction of hypoglycemia in random order. In Study 2, patients hospitalized for hypoglycemia and matched controls were compared. Circulating stem cells and EPCs were measured by flow cytometry based on the expression of CD34 and kinase insert domain receptor (KDR). In Study 1, the physiologic decline of CD34+KDR+ EPCs from 8 am to 2 pm was abolished by insulin-induced hypoglycemia in type 1 diabetic patients. In Study 2, diabetic patients hospitalized for severe iatrogenic hypoglycemia had significantly lower levels of CD34+ stem cells and CD34+KDR+ EPCs compared with diabetic inpatients or outpatient controls. In diabetic patients, a single mild hypoglycemic episode can compromise the physiologic EPC fluctuation, whereas severe hypoglycemia is associated with a marked reduction in stem cells and EPCs. These data provide a possible link between hypoglycemia and adverse outcomes of diabetes.

A contextual perspective on talented female participants and their development in extracurricular STEM programs.

PubMed

Stoeger, Heidrun; Schirner, Sigrun; Laemmle, Lena; Obergriesser, Stefanie; Heilemann, Michael; Ziegler, Albert

2016-08-01

We advocate a more contextual perspective in giftedness research. In our view, doing so opens up three particularly interesting research areas, which we refer to as the participation issue, the effectiveness issue, and the interaction issue. To illustrate their utility, we examined characteristics of females participating in German high achiever-track secondary education who had applied for participation in a 1-year extracurricular e-mentoring program in science, technology, engineering, and mathematics (STEM) (n = 1237). Their characteristics were compared with male and female random-sample control groups. We assessed the effectiveness of the mentoring program by comparing the developmental trajectories of program participants with those of three control groups: applicants who were randomly chosen for later participation (waiting-list control group) and a female and a male control group. Finally, we examined whether differences in program effectiveness could be partially explained by characteristics of the interaction with the domain. Program applicants possessed more advantageous individual characteristics but, unexpectedly, less advantageous home and school environments than female and male members of the control groups. Program participation affected positive changes in certainty about career goals (independent of STEM) and in the number of STEM activities. The amount of STEM communication partially explained differences in program effectiveness. © 2016 New York Academy of Sciences.

Stem cell-based biological tooth repair and regeneration

PubMed Central

Volponi, Ana Angelova; Pang, Yvonne; Sharpe, Paul T.

2010-01-01

Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease. PMID:21035344

Latent palmprint matching.

PubMed

Jain, Anil K; Feng, Jianjiang

2009-06-01

The evidential value of palmprints in forensic applications is clear as about 30 percent of the latents recovered from crime scenes are from palms. While biometric systems for palmprint-based personal authentication in access control type of applications have been developed, they mostly deal with low-resolution (about 100 ppi) palmprints and only perform full-to-full palmprint matching. We propose a latent-to-full palmprint matching system that is needed in forensic applications. Our system deals with palmprints captured at 500 ppi (the current standard in forensic applications) or higher resolution and uses minutiae as features to be compatible with the methodology used by latent experts. Latent palmprint matching is a challenging problem because latent prints lifted at crime scenes are of poor image quality, cover only a small area of the palm, and have a complex background. Other difficulties include a large number of minutiae in full prints (about 10 times as many as fingerprints), and the presence of many creases in latents and full prints. A robust algorithm to reliably estimate the local ridge direction and frequency in palmprints is developed. This facilitates the extraction of ridge and minutiae features even in poor quality palmprints. A fixed-length minutia descriptor, MinutiaCode, is utilized to capture distinctive information around each minutia and an alignment-based minutiae matching algorithm is used to match two palmprints. Two sets of partial palmprints (150 live-scan partial palmprints and 100 latent palmprints) are matched to a background database of 10,200 full palmprints to test the proposed system. Despite the inherent difficulty of latent-to-full palmprint matching, rank-1 recognition rates of 78.7 and 69 percent, respectively, were achieved in searching live-scan partial palmprints and latent palmprints against the background database.

Category-based guidance of spatial attention during visual search for feature conjunctions.

PubMed

Nako, Rebecca; Grubert, Anna; Eimer, Martin

2016-10-01

The question whether alphanumerical category is involved in the control of attentional target selection during visual search remains a contentious issue. We tested whether category-based attentional mechanisms would guide the allocation of attention under conditions where targets were defined by a combination of alphanumerical category and a basic visual feature, and search displays could contain both targets and partially matching distractor objects. The N2pc component was used as an electrophysiological marker of attentional object selection in tasks where target objects were defined by a conjunction of color and category (Experiment 1) or shape and category (Experiment 2). Some search displays contained the target or a nontarget object that matched either the target color/shape or its category among 3 nonmatching distractors. In other displays, the target and a partially matching nontarget object appeared together. N2pc components were elicited not only by targets and by color- or shape-matching nontargets, but also by category-matching nontarget objects, even on trials where a target was present in the same display. On these trials, the summed N2pc components to the 2 types of partially matching nontargets were initially equal in size to the target N2pc, suggesting that attention was allocated simultaneously and independently to all objects with target-matching features during the early phase of attentional processing. Results demonstrate that alphanumerical category is a genuine guiding feature that can operate in parallel with color or shape information to control the deployment of attention during visual search. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

An Investigation of Same- versus Cross-Gender Matching for Boys in Formal School-Based Mentoring Programs

ERIC Educational Resources Information Center

Kanchewa, Stella S.; Rhodes, Jean E.; Schwartz, Sarah E. O.; Olsho, Lauren E. W.

2014-01-01

Although assigned mentoring relationships have typically involved same-gender matches, a growing number of programs, particularly those in schools, have begun pairing female mentors with male mentees. This practice stems, in large part, from the relative dearth of male mentors and programs' efforts to increase the availability of youth mentoring…

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

PubMed Central

Zhuang, Lei; Zhang, Jun; Xiang, Xin

2007-01-01

Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

PubMed

Samuel, G N; Strong, K A; Kerridge, I; Jordens, C F C; Ankeny, R A; Shaw, P J

2009-04-01

Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.

Graft-versus-host disease after radiation therapy in patients who have undergone allogeneic stem cell transplantation: two case reports.

PubMed

Milgrom, Sarah A; Nieto, Yago; Pinnix, Chelsea C; Smith, Grace L; Wogan, Christine F; Rondon, Gabriela; Medeiros, L Jeffrey; Kebriaei, Partow; Dabaja, Bouthaina S

2016-07-28

Patients who undergo allogeneic stem cell transplantation and subsequent radiation therapy uncommonly develop graft-versus-host disease within the irradiated area. We quantified the incidence of this complication, which is a novel contribution to the field. From 2010 to 2014, 1849 patients underwent allogeneic stem cell transplantation, and 41 (2 %) received radiation therapy afterward. Of these, two patients (5 %) developed graft-versus-host disease within the irradiated tissues during or immediately after radiation therapy. The first patient is a 37-year-old white man who had Hodgkin lymphoma; he underwent allogeneic stem cell transplantation from a matched unrelated donor and received radiation therapy for an abdominal and pelvic nodal recurrence. After 28.8 Gy, he developed grade 4 gastrointestinal graft-versus-host disease, refractory to tacrolimus and steroids, but responsive to pentostatin and photopheresis. The other patient is a 24-year-old white man who had acute leukemia; he underwent allogeneic stem cell transplantation from a matched related donor and received craniospinal irradiation for a central nervous system relapse. After 24 cobalt Gy equivalent, he developed severe cutaneous graft-versus-host disease, sharply delineated within the radiation therapy field, which was responsive to tacrolimus and methylprednisolone. We conclude that graft-versus-host disease within irradiated tissues is an uncommon but potentially serious complication that may follow radiation therapy in patients who have undergone allogeneic stem cell transplantation. Clinicians must be aware of this complication and prepared with strategies to mitigate risk. Patients who have undergone allogeneic stem cell transplantation represent a unique population that may offer novel insight into the pathways involved in radiation-related inflammation.

The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

PubMed

Udani, V M

2006-02-01

Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

The Online STEM Classroom--Who Succeeds? An Exploration of the Impact of Ethnicity, Gender, and Non-Traditional Student Characteristics in the Community College Context

ERIC Educational Resources Information Center

Wladis, Claire; Conway, Katherine M.; Hachey, Alyse C.

2015-01-01

Objective: This study analyzes how ethnicity, gender, and non-traditional student characteristics relate to differential online versus face-to-face outcomes in science, technology, engineering, and mathematics (STEM) courses at community colleges. Method: This study used a sample of 3,600 students in online and face-to-face courses matched by…

Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea.

PubMed

Hildebrand, Michael S; Dahl, Hans-Henrik M; Hardman, Jennifer; Coleman, Bryony; Shepherd, Robert K; de Silva, Michelle G

2005-12-01

The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

PubMed Central

Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Hardman, Jennifer; Coleman, Bryony; Shepherd, Robert K.

2005-01-01

The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment. PMID:16208453

CD44 Is a Negative Cell Surface Marker for Pluripotent Stem Cell Identification during Human Fibroblast Reprogramming

PubMed Central

Vaz, Candida; Tanavde, Vivek; Lakshmipathy, Uma

2014-01-01

Induced pluripotent stem cells (iPSCs) are promising tools for disease research and cell therapy. One of the critical steps in establishing iPSC lines is the early identification of fully reprogrammed colonies among unreprogrammed fibroblasts and partially reprogrammed intermediates. Currently, colony morphology and pluripotent stem cell surface markers are used to identify iPSC colonies. Through additional clonal characterization, we show that these tools fail to distinguish partially reprogrammed intermediates from fully reprogrammed iPSCs. Thus, they can lead to the selection of suboptimal clones for expansion. A subsequent global transcriptome analysis revealed that the cell adhesion protein CD44 is a marker that differentiates between partially and fully reprogrammed cells. Immunohistochemistry and flow cytometry confirmed that CD44 is highly expressed in the human parental fibroblasts used for the reprogramming experiments. It is gradually lost throughout the reprogramming process and is absent in fully established iPSCs. When used in conjunction with pluripotent cell markers, CD44 staining results in the clear identification of fully reprogrammed cells. This combination of positive and negative surface markers allows for easier and more accurate iPSC detection and selection, thus reducing the effort spent on suboptimal iPSC clones. PMID:24416407

Striking Similarity in the Gene Expression Levels of Individual Myc Module Members among ESCs, EpiSCs, and Partial iPSCs

PubMed Central

Hirasaki, Masataka; Hiraki-Kamon, Keiko; Kamon, Masayoshi; Suzuki, Ayumu; Katano, Miyuki; Nishimoto, Masazumi; Okuda, Akihiko

2013-01-01

Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs). Epiblast stem cells (EpiSCs) are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs) and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties. PMID:24386274

An investigation into western white pine partial resistance against the rust pathogen Cronartium ribicola using in vitro screening method

Treesearch

D. Noshad; J.N. King

2012-01-01

Cronartium ribicola is one of the most destructive forest pathogens of North American white pines. The pathogen infects pine trees through their stomata, colonizes the stem, and produces stem cankers the following growing season. In this research, we collected samples from different white pine populations across Canada and the United States to...

Stereo Sound Field Controller Design Using Partial Model Matching on the Frequency Domain

NASA Astrophysics Data System (ADS)

Kumon, Makoto; Miike, Katsuhiro; Eguchi, Kazuki; Mizumoto, Ikuro; Iwai, Zenta

The objective of sound field control is to make the acoustic characteristics of a listening room close to those of the desired system. Conventional methods apply feedforward controllers, such as digital filters, to achieve this objective. However, feedback controllers are also necessary in order to attenuate noise or to compensate the uncertainty of the acoustic characteristics of the listening room. Since acoustic characteristics are well modeled on the frequency domain, it is efficient to design controllers with respect to frequency responses, but it is difficult to design a multi input multi output (MIMO) control system on a wide frequency domain. In the present study, a partial model matching method on the frequency domain was adopted because this method requires only sampled data, rather than complex mathematical models of the plant, in order to design controllers for MIMO systems. The partial model matching method was applied to design two-degree-of-freedom controllers for acoustic equalization and noise reduction. Experiments demonstrated effectiveness of the proposed method.

Partial regeneration of uterine horns in rats through adipose-derived stem cell sheets.

PubMed

Sun, Huijun; Lu, Jie; Li, Bo; Chen, Shuqiang; Xiao, Xifeng; Wang, Jun; Wang, Jingjing; Wang, Xiaohong

2018-06-20

Severe uterine damage and infection lead to intrauterine adhesions, which result in hypomenorrhea, amenorrhea and infertility. Cell sheet engineering has shown great promise in clinical applications. Adipose-derived stem cells (ADSCs) are emerging as an alternative source of stem cells for cell-based therapies. In the present study, we investigated the feasibility of applying ADSCs as seed cells to form scaffold-free cell sheet. Data showed that ADSC sheets expressed higher levels of FGF, Col I, TGFβ and VEGF than ADSCs in suspension, while increased expression of this gene set was associated with stemness, including Nanog, Oct4 and Sox2. We then investigated the therapeutic effects of 3D ADSCs sheet on regeneration in a rat model. We found that ADSCs were mainly detected in the basal layer of the regenerating endometrium in the cell sheet group at 21 days after transplantation. Additionally, some ADSCs differentiated into stromal-like cells. Moreover, ADSC sheets transplanted into partially excised uteri promoted regeneration of the endometrium cells, muscle cells and stimulated angiogenesis, and also resulted in better pregnancy outcomes. Therefore, ADSC sheet therapy shows considerable promise as a new treatment for severe uterine damage.

Early development of matched planted and naturally regenerated Douglas-fir stands after slash burning in the Cascade Range.

Treesearch

R.E. Miller; R.E. Bigley; S. Webster

1993-01-01

We compared matched planted and naturally regenerated plots in 35- to 38- year-old Douglas-fir (Pseudotsuga menziesii var. menziesii) stands at seven locations in western Washington and Oregon. Total number of live stems is similar, but stands planted to Douglas fir average 26 more live stemslac of Douglas-fir and 39 fewer...

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.

Hexafluoroisopropanol-induced helix-sheet transition of stem bromelain: correlation to function.

PubMed

Dave, Sandeep; Dkhar, H Kitdorlang; Singh, Manvendra Pratap; Gupta, Garima; Chandra, Vemika; Mahajan, Sahil; Gupta, Pawan

2010-06-01

Stem bromelain is a proteolytic phytoprotein with a variety of therapeutic effects. Understanding its structural properties could provide insight into the mechanisms underlying its clinical utility. Stem bromelain was evaluated for its conformational and folding properties at the pH conditions it encounters when administered orally. It exists as a partially folded intermediate at pH 2.0. The conformational changes to this intermediate state were evaluated using fluorinated alcohols known to induce changes similar to those seen in vivo. Studies using circular dichroism, fluorescence emission spectroscopy, binding of the hydrophobic dye 1-anilino-8-naphthalene sulfonic acid and mass spectrometry indicate that treatment with 10-30% hexafluoroisopropanol induces the partially folded intermediate to adopt much of the native protein's secondary structure, but only a rudimentary tertiary structure, characteristic of the molten globule state. Addition of slightly higher concentrations of hexafluoroisopropanol caused transformation from an alpha-helix to a beta-sheet and induced formation of a compact nonnative structure. This nonnative form was more inhibitory of cell survival than either the native or the partially folded intermediate forms, as measured by enhanced suppression of proliferative cues (e.g., extracellular-signal-regulated kinase) and initiation of apoptotic events. The nonnative form also showed better antitumorigenic properties, as evaluated using an induced two-stage mouse skin papilloma model. In contrast, the nonnative state showed only a fraction of the proteolytic activity of the native form. This study demonstrates that hexafluoroisopropanol can induce a conformational change in stem bromelain to a form with potentially useful therapeutic properties different from those of the native protein. Copyright 2010 Elsevier Ltd. All rights reserved.

Recent advances in electron tomography: TEM and HAADF-STEM tomography for materials science and semiconductor applications.

PubMed

Kübel, Christian; Voigt, Andreas; Schoenmakers, Remco; Otten, Max; Su, David; Lee, Tan-Chen; Carlsson, Anna; Bradley, John

2005-10-01

Electron tomography is a well-established technique for three-dimensional structure determination of (almost) amorphous specimens in life sciences applications. With the recent advances in nanotechnology and the semiconductor industry, there is also an increasing need for high-resolution three-dimensional (3D) structural information in physical sciences. In this article, we evaluate the capabilities and limitations of transmission electron microscopy (TEM) and high-angle-annular-dark-field scanning transmission electron microscopy (HAADF-STEM) tomography for the 3D structural characterization of partially crystalline to highly crystalline materials. Our analysis of catalysts, a hydrogen storage material, and different semiconductor devices shows that features with a diameter as small as 1-2 nm can be resolved in three dimensions by electron tomography. For partially crystalline materials with small single crystalline domains, bright-field TEM tomography provides reliable 3D structural information. HAADF-STEM tomography is more versatile and can also be used for high-resolution 3D imaging of highly crystalline materials such as semiconductor devices.

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

PubMed

Stefanova, Z; Neychev, H; Ivanovska, N; Kostova, I

1995-05-01

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Novel quantitative trait loci for partial resistance to Phytophthora sojae in soybean PI 398841

USDA-ARS?s Scientific Manuscript database

Phytophthora root and stem rot caused by Phytophthora sojae Kaufmann and Gerdmann is one of the most severe soybean [Glycine max (L.) Merr] diseases in the US. Partial resistance is as effective in managing this disease as single-gene (Rps) mediated resistance and is more durable. The objective of t...

Eta Squared, Partial Eta Squared, and Misreporting of Effect Size in Communication Research.

ERIC Educational Resources Information Center

Levine, Timothy R.; Hullett, Craig R.

2002-01-01

Alerts communication researchers to potential errors stemming from the use of SPSS (Statistical Package for the Social Sciences) to obtain estimates of eta squared in analysis of variance (ANOVA). Strives to clarify issues concerning the development and appropriate use of eta squared and partial eta squared in ANOVA. Discusses the reporting of…

DOE/Industry Matching Grant Program

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

John C. Lee

2003-09-30

For the academic year 2001-2002, the Department of Nuclear Engineering and Radiological Sciences received $50,000 of industrial contributions, matched by a DOE grant of $35,000. We used the combined DOE/Industry Matching Grant of $85,000 toward (a) undergraduate merit scholarships and research support, (b) graduate student support, and (c) partial support of a research scientist.

Biologic Approaches for the Treatment of Partial Tears of the Anterior Cruciate Ligament

PubMed Central

Dallo, Ignacio; Chahla, Jorge; Mitchell, Justin J.; Pascual-Garrido, Cecilia; Feagin, John A.; LaPrade, Robert F.

2017-01-01

Background: Anterior cruciate ligament reconstruction (ACLR) has been established as the gold standard for treatment of complete ruptures of the anterior cruciate ligament (ACL) in active, symptomatic individuals. In contrast, treatment of partial tears of the ACL remains controversial. Biologically augmented ACL-repair techniques are expanding in an attempt to regenerate and improve healing and outcomes of both the native ACL and the reconstructed graft tissue. Purpose: To review the biologic treatment options for partial tears of the ACL. Study Design: Review. Methods: A literature review was performed that included searches of PubMed, Medline, and Cochrane databases using the following keywords: partial tear of the ACL, ACL repair, bone marrow concentrate, growth factors/healing enhancement, platelet-rich plasma (PRP), stem cell therapy. Results: The use of novel biologic ACL repair techniques, including growth factors, PRP, stem cells, and bioscaffolds, have been reported to result in promising preclinical and short-term clinical outcomes. Conclusion: The potential benefits of these biological augmentation approaches for partial ACL tears are improved healing, better proprioception, and a faster return to sport and activities of daily living when compared with standard reconstruction procedures. However, long-term studies with larger cohorts of patients and with technique validation are necessary to assess the real effect of these approaches. PMID:28210653

Biologic agents for anterior cruciate ligament healing: A systematic review

PubMed Central

Di Matteo, Berardo; Loibl, Markus; Andriolo, Luca; Filardo, Giuseppe; Zellner, Johannes; Koch, Matthias; Angele, Peter

2016-01-01

AIM To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing. METHODS A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing. RESULTS The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series. CONCLUSION There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement. PMID:27672573

Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

PubMed

Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

2018-05-01

Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

Effect of berberine on the viability of adipose tissue-derived mesenchymal stem cells in nutrients deficient condition.

PubMed

Ghorbani, Ahmad; Baradaran Rahimi, Vafa; Sadeghnia, Hamid Reza; Hosseini, Azar

2018-03-01

This study was designed to examine whether berberine protects rat adipose tissue-derived stem cells (ASCs) against glucose and serum deprivation (GSD)-induced cell death. ASCs were cultured for 24 h in GSD condition in the presence of berberine and then cell viability, apoptosis and generation of reactive oxygen species (ROS) were evaluated. The GSD condition significantly decreased ASCs viability and increased ROS generation and apoptosis. Incubation with 0.75-3 μM berberine partially increased cell viability and decreased ROS generation and apoptosis in GSD condition. In conclusion, berberine partially protects ASCs in nutrients deficient condition and may help ASCs to preserve their survival during cell therapy of ischemia.

Allogeneic Transplantation: Peripheral Blood versus Bone Marrow

PubMed Central

Bensinger, William I.

2013-01-01

Purpose of Review Peripheral Blood Stem Cells (PBSC) have been widely adopted as a source of stem cells for allogeneic transplantation although controversy remains regarding their role compared to the use of bone marrow (BM). Recent Findings Ten year follow-up has been reported from several large randomized trials and a recently completed trial using unrelated donor stem cells have been reported. In addition, two meta-analyses have been reported from the findings of a number of randomized studies. Several studies indicate that PBSC confer survival advantages over BM with matched sibling donors for most disease categories except where the risks of disease recurrence within the first year are low, but with the extra risk of more chronic GVHD. Using PBSC from unrelated donors does not appear to be more beneficial than BM, but with early follow-up. New strategies for rapid mobilization of PBSC from normal donors using plerixafor have been reported. Early studies suggest that filgrastim stimulated BM may confer some of the advantages of PBSC without the risks of chronic GVHD. Summary PBSC are a preferred source of stem cells for many types of allogeneic transplant where matched related donors are available. Whether the same benefits accrue from unrelated donors will require further follow-up. PMID:22185938

Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy.

PubMed

Jiang, Hua; Jiang, Min-Yan; Liu, Sha; Cai, Yan-Na; Liang, Cui-Li; Liu, Li

2015-08-01

Childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30% of patients who might benefit from a hematopoietic stem cell transplant will have a full human leukocyte antigen-matched donor, which is considered to be the best choice. We present a 5-year-old boy with cerebral X-linked adrenoleukodystrophy whose brain magnetic resonance imaging severity score was 7 and who needed an immediate transplantation without an available full human leukocyte antigen-matched donor. We combined haploidentical and umbilical cord blood sources for transplantation and saw encouraging results. After transplantation, the patient showed neurological stability for 6 months and the level of very long chain fatty acids had decreased. By 1 year, the patient appeared to gradually develop cognition, motor, and visual disturbances resulting from possible mix chimerism. Transplantation of haploidentical stem cells combined with the infusion of umbilical cord blood is a novel approach for treating cerebral X-linked adrenoleukodystrophy. It is critical to monitor posttransplant chimerism and carry out antirejection therapy timely for a beneficial clinical outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Form recovery by understory sugar maple under uneven-aged management

Treesearch

George R., Jr. Trimble

1968-01-01

A study of advanced sugar maple reproduction on a good site in West Virginia indicated that considerable improvement of stem form takes place after selection cutting in the overstory. The study stems were 1 to 6 inches in d.b.h. and many of them were over 50 years old. To an appreciable extent, flat bps and minor crooks were overcome after partial release.

Exploring Teachers' and Students' Gender Role Bias and Students' Confidence in STEM Fields

ERIC Educational Resources Information Center

Hand, Sarah; Rice, Lindsay; Greenlee, Eric

2017-01-01

There is a shortfall of girls and women pursuing STEM disciplines, a deficit that may be partially attributed to subtle forms of bias that are tied to traditional gender role stereotypes. The current study examined these subtle biases in high school teachers and students in two ways: by asking teachers and students to attribute masculine and…

Effect of wheat stem sawfly damage on yield and quality of selected Canadian spring wheat.

PubMed

Beres, B L; Cárcamo, H A; Byers, J R

2007-02-01

The wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), has reached outbreak status at most locations in the southern Canadian prairies. Solid-stemmed wheat, Triticum aestivum L., cultivars, which are less susceptible to damage, remain the primary management option. This article quantifies the effect of wheat stem sawfly damage on grain yield and quality at harvest and determines how cultivar selection affects harvest losses. Solid-stemmed cultivars were compared with hollow-stemmed cultivars and with blends of a 1:1 ratio of each. The hollow-stemmed cultivars with the exception of'McKenzie', which had intermediate levels of stem cutting, were all significantly more susceptible to stem cutting than solid-stemmed cultivars. Cultivar blends had lower damage but were still significantly higher than the solid-stemmed cultivars. The solid-stemmed 'AC Eatonia' and 'AC Abbey' had the lowest levels of stem cutting and ranked second and third overall for yield in 2001 and 2002. McKenzie ranked first, which reflects its yield potential in combination with its partial resistance to stem cutting. Lower cutting in AC Eatonia, AC Abbey, McKenzie, and the blend of AC Abbey/ McKenzie was significantly correlated with lower grain losses. Grain lost at harvest has major economic implications if sawfly pressure is moderate to high and susceptible cultivars predominate.

Intra-articular Implantation of Mesenchymal Stem Cells, Part 2

PubMed Central

Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

2017-01-01

Knee osteoarthritis (OA) after partial or total meniscectomy is a prevalent issue that patients must face. Various methods of replacing meniscal tissue have been studied to avoid this progression, including meniscal allograft transplantation, meniscal scaffolds, and synthetic meniscus replacement. Studies have shown that meniscal scaffolds may improve symptoms but have not been shown to prevent progression of OA. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible biological therapy for meniscal regeneration. Several animal studies and 1 human study have evaluated the effect of transplanting MSCs into the knee joint after partial meniscectomy. The purpose of this review was to assess the outcomes of intra-articular transplantation of MSCs on meniscal regeneration in animals and humans after partial meniscectomy. Limited results from animal studies suggest that there is some potential for intra-articular injection of MSCs for the regeneration of meniscal tissue. However, further studies are necessary to determine the quality of regenerated meniscal tissue through histological and biomechanical testing. PMID:28203596

A Comparison of State Test Performances of Public Schools and a Charter School System in Old and New Testing in Texas

ERIC Educational Resources Information Center

Sahin, Alpaslan; Almus, Kadir; Willson, Victor

2017-01-01

This study examined the high schools' state tests performances in mathematics, reading, and science of an open-enrollment STEM-focused charter school system,Harmony Public Schools(HPS), between 2010 and 2013, and compared them with the performance of matched traditional public schools (TPS) in Texas. After propensity score matching, 12 HPS schools…

Mismatched related hematopoietic stem cell transplantation in primary immunodeficiency.

PubMed

Wahadneh, Adel M; Bin Dahman, Haifa A; Abu Shukear, Mohammed E; Habahbeh, Zeyad M; Ajarmeh, Mohammad A; Zyood, Raed M; Habashneh, Mueen S

2013-11-01

Hematopoietic stem cell transplantation (HSCT) is the definitive therapy for a variety of primary immunodeficiency syndromes (PIDs). However, no more than 30% of the patients will have a human leukocyte antigen (HLA)-identical sibling. We retrospectively analyzed our results of ten patients with PID; severe combined immunodeficiency (SCID) (n = 7), hyper IgM (HIgM) (n = 1) and combined immunodeficiency (CID) (n = 2), who lacked a fully matched donor and underwent mismatched related HSCT during the period from 2008 to 2010. The median age at the time of transplantation ranged between 3 and 84 months (median 6.5 months). Peripheral blood stem cells (PBSC) were used in all HSCTs. The mean value of the peripheral CD34+ cells infused was 9.19 × 10 (6) /kg recipient weight. Patients received different conditioning protocols. All patients received anti graft versus host disease (GVHD) prophylaxis and all were engrafted. Mixed chimerism (5-55%) was noticed. GVHD was observed in 50% of the patients. Post-transplant follow-up ranged from 3 weeks to 36 months (median 15 months). Five patients are still alive while one patient developed engraftment syndrome followed by graft slippage for which a second transplant with CD34+ stem cells 5.8 × 10 (6) /kg recipient's weight was infused. The others died from sepsis and transplant-related complications. Immune reconstitution was noticed in four patients. In conclusion, HLA-haploidentical stem cell transplantation may be feasible, with appropriate GVHD prophylaxis, for patients with PID who lack a fully matched donor.

Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

PubMed Central

Rådestad, E.; Wikell, H.; Engström, M.; Watz, E.; Sundberg, B.; Thunberg, S.; Uzunel, M.; Mattsson, J.; Uhlin, M.

2014-01-01

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the αβ T-cell receptor and the remaining T-cells express the γδ T-cell receptor. As αβ T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with αβ T-cell depleted stem cell boosts. The majority of γδ T-cells in the grafts expressed Vδ2 and/or Vγ9. Most patients receiving αβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study. PMID:25371909

Gravitropism in higher plant shoots. IV - Further studies on participation of ethylene

NASA Technical Reports Server (NTRS)

Wheeler, Raymond M.; White, Rosemary G.; Salisbury, Frank B.

1986-01-01

Various hypotheses regarding the influence of ethylene on gravitropism in higher plant shoots were experimentally tested. It was found that ethylene at 1.0 and 10.0 cu cm/cu m decreased the rate of gravitropic bending in cocklebur stems, while 0.1 cm/cu m of ethylene had little effect. Treating cocklebur plants with 1.0 mmol aminoethoxyvinylglycine (AVG, an ethylene synthesis inhibitor) delayed stem bending compared with controls, but adding 0.1 cu cm/cu m ethylene in the surrounding atmosphere partially restored the rate of bending of AVG-treated plants. Virtually all newly synthesized ethylene appeared in bottom halves of horizontal stems, where ethylene concentrations were as much as 100 times those in upright stems or in top halves of horizontal stems. Auxin applied to one side of a vertical stem caused extreme bending away from that side; gibberellic acid, kinetin, and abscisic acid were without effect.

Analysis of Stem Cell Motility In Vivo Based on Immunodetection of Planarian Neoblasts and Tracing of BrdU-Labeled Cells After Partial Irradiation.

PubMed

Tasaki, Junichi; Uchiyama-Tasaki, Chihiro; Rouhana, Labib

2016-01-01

Planarian flatworms have become an important system for the study of stem cell behavior and regulation in vivo. These organisms are able to regenerate any part of their body upon damage or amputation. A crucial cellular event in the process of planarian regeneration is the migration of pluripotent stem cells (known as neoblasts) to the site of injury. Here we describe two approaches for analyzing migration of planarian stem cells to an area where these have been ablated by localized X-ray irradiation. The first approach involves immunolabeling of mitotic neoblasts, while the second is based on tracing stem cells and their progeny after BrdU incorporation. The use of planarians in studies of cell motility is suitable for the identification of factors that influence stem cell migration in vivo and is amenable to RNA interference or pharmacological screening.

A Comparison of Oak Regeneration Conditions Following Midstory Injection and Partial Overstory Removal in a Tombigbee River Terrace

Treesearch

Stephen E. Peairs; Andrew W. Ezell; Keith L. Belli; John D. Hodges

2004-01-01

Bottomland hardwood stands comprised of a large oak component can be regenerated through natural oak regeneration. To maximize oak regeneration potential, the stand manager must practice silvicultural techniques that allow for necessary sunlight penetration to reach the forest floor. Control of stems occupying the midstory/understory and partial overstory removal are...

Variation in chromosome constitution of the Xiaoyan series partial amphiploids and its relations to stripe rust and stem rust resistance

USDA-ARS?s Scientific Manuscript database

In the tertiary gene pool of wheat, tall wheatgrass Thinopyrum ponticum (2n = 10x = 70) is an excellent source of resistance genes against numerous wheat diseases. The creation of wheat-Th. ponticum partial amphiploids is an intermediate step for transferring the useful genes from Th. ponticum to w...

Laser Stimulated Genomic Exchange in Stem Cells. Laser Non-cloning Techniques

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2012-02-01

I propose a novel technique for a pluripotent stem cell generation. Genomic exchange is stimulated by the beat-wave free electron laser, (B-W FEL), frequency matching with the frequencies of the DNAootnotetextJ.D. Watson and F. H. C. Crick, Nature, 171, 737-738 (1953). eigen-oscillations. B-W FEL-1ootnotetextV. Stefan, B.I.Cohen, C. Joshi Science, 243,4890, (Jan 27,1989); Stefan, et al., Bull. APS. 32, No. 9, 1713 (1987); Stefan, APS March-2011, #S1.143; APS- March-2009, #K1.276. scans entire stem cell; B-W FEL-2 probes the chromosomes. The scanning and probing lasers: 300-500nm and 100-300nm, respectively; irradiances: the order-of-10s mW/cm^2 (above the threshold value for a particular gene structure); repetition rate of few-100s Hz. A variety of genetic-matching conditions can be arranged. Genomic glitches, (the cell nucleus transferootnotetextScott Noggle et al. Nature, 478, 70-75 (06 October 2011).), can be hedged by the use of lasers.

Sutureless amniotic membrane transplantation for partial limbal stem cell deficiency.

PubMed

Kheirkhah, Ahmad; Casas, Victoria; Raju, Vadrevu K; Tseng, Scheffer C G

2008-05-01

To evaluate the results of sutureless amniotic membrane (AM) transplantation using fibrin glue for reconstructing corneal surfaces with partial limbal stem cell deficiency (LSCD). Retrospective noncomparative interventional case series. Eleven eyes of nine patients that had LSCD with 120 degrees to almost 360 degrees of limbal involvement underwent superficial keratectomy to remove the conjunctivalized pannus followed by AM transplantation using fibrin glue. Additional sutureless AM patch (ProKera; Bio-Tissue, Inc, Miami, Florida, USA) was used in seven patients, and mitomycin C was applied on the cornea in four eyes and during fornix reconstruction in seven eyes. The surgery was repeated in three eyes for residual pannus. During a mean follow-up of 14.2 +/- 7.7 months (range, six to 26 months), all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect, and showed less stromal cloudiness and vascularization. Best-corrected visual acuity improved in nine eyes (81.8%). Corneal epithelialization proceeded by epithelial growth over AM (n = 4), accompanied by dissolution of AM (n = 4) or a combination of both (n = 3). No complication was noted regarding initial or repeated uses of fibrin glue. AM transplantation using fibrin glue appears to be a safe and effective method of restoring a stable corneal epithelium for cases with partial LSCD. This approach avoids the need of transplanting limbal epithelial stem cells.

Electrophysiological evidence for parts and wholes in visual face memory.

PubMed

Towler, John; Eimer, Martin

2016-10-01

It is often assumed that upright faces are represented in a holistic fashion, while representations of inverted faces are essentially part-based. To assess this hypothesis, we recorded event-related potentials (ERPs) during a sequential face identity matching task where successively presented pairs of upright or inverted faces were either identical or differed with respect to their internal features, their external features, or both. Participants' task was to report on each trial whether the face pair was identical or different. To track the activation of visual face memory representations, we measured N250r components that emerge over posterior face-selective regions during the activation of visual face memory representations by a successful identity match. N250r components to full identity repetitions were smaller and emerged later for inverted as compared to upright faces, demonstrating that image inversion impairs face identity matching processes. For upright faces, N250r components were also elicited by partial repetitions of external or internal features, which suggest that the underlying identity matching processes are not exclusively based on non-decomposable holistic representations. However, the N250r to full identity repetitions was super-additive (i.e., larger than the sum of the two N250r components to partial repetitions of external or internal features) for upright faces, demonstrating that holistic representations were involved in identity matching processes. For inverted faces, N250r components to full and partial identity repetitions were strictly additive, indicating that the identity matching of external and internal features operated in an entirely part-based fashion. These results provide new electrophysiological evidence for qualitative differences between representations of upright and inverted faces in the occipital-temporal face processing system. Copyright © 2016 Elsevier Ltd. All rights reserved.

A triple murder.

PubMed

Vidanapathirana, M; Ruwanpura, P R; Ariyaratne, D; Karunanayake, D S K

2015-12-01

Three partially burnt bodies were found in a burnt out bedroom. A candle and matches were found on a partially burnt bed, suggesting accidental deaths. Careful scene analysis and forensic post-mortems demonstrated that this was a multiple murder rather than an accident. © The Author(s) 2015.

How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

PubMed

Kohn, Donald B; Gaspar, H Bobby

2017-05-01

Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential

PubMed Central

Kaneko, Kunihiko

2011-01-01

The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID:22073296

Drosophila Glypicans Regulate Follicle Stem Cell Maintenance and Niche Competition.

PubMed

Su, Tsu-Yi; Nakato, Eriko; Choi, Pui Yee; Nakato, Hiroshi

2018-04-09

Adult stem cells reside in specialized microenvironments, called niches, which provide signals for stem cells to maintain their undifferentiated and self-renewing state. To maintain stem cell quality, several types of stem cells are known to be regularly replaced by progenitor cells through niche competition. However, the cellular and molecular bases for stem cell competition for niche occupancy are largely unknown. Here, we show that two Drosophila members of the glypican family of heparan sulfate proteoglycans (HSPGs), Dally and Dally-like (Dlp), differentially regulate follicle stem cell (FSC) maintenance and FSC competitiveness for niche occupancy. Lineage analyses of glypican mutant FSC clones showed that dally is essential for normal FSC maintenance. In contrast, dlp is a hyper-competitive mutation: dlp mutant FSC progenitors often eventually occupy the entire epithelial sheet. RNAi knockdown experiments showed that Dally and Dlp play both partially redundant and distinct roles in regulating Jak/Stat, Wg and Hh signaling in FSCs. The Drosophila FSC system offers a powerful genetic model to study the mechanisms by which HSPGs exert specific functions in stem cell replacement and competition. Copyright © 2018, Genetics.

Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

PubMed

Chang, Ying-Jun; Huang, Xiao-Jun

2011-01-01

In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G-CSF-stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation. © 2010 John Wiley & Sons A/S.

Optimization of a matched-filter receiver for frequency hopping code acquisition in jamming

NASA Astrophysics Data System (ADS)

Pawlowski, P. R.; Polydoros, A.

A matched-filter receiver for frequency hopping (FH) code acquisition is optimized when either partial-band tone jamming or partial-band Gaussian noise jamming is present. The receiver is matched to a segment of the FH code sequence, sums hard per-channel decisions to form a test, and uses multiple tests to verify acquisition. The length of the matched filter and the number of verification tests are fixed. Optimization is then choosing thresholds to maximize performance based upon the receiver's degree of knowledge about the jammer ('side-information'). Four levels of side-information are considered, ranging from none to complete. The latter level results in a constant-false-alarm-rate (CFAR) design. At each level, performance sensitivity to threshold choice is analyzed. Robust thresholds are chosen to maximize performance as the jammer varies its power distribution, resulting in simple design rules which aid threshold selection. Performance results, which show that optimum distributions for the jammer power over the total FH bandwidth exist, are presented.

Acquired Aplastic Anemia: What Have We Learned and What Is in the Horizon?

PubMed

Savaşan, Süreyya

2018-06-01

Acquired aplastic anemia (aAA) characterized by peripheral pancytopenia and bone marrow aplasia is a rare and serious disorder. Differential diagnosis includes constitutional bone marrow failure syndromes and myelodysplastic disorders. Autoimmune reaction to altered hematopoietic stem cells highlights the underlying mechanism. Matched related donor allogeneic hematopoietic stem cell transplantation is the ideal pediatric treatment; alternative approaches include immunosuppressive therapy and use of eltrombopag. Progression to clonal disorders can occur. Recently, alternative donor hematopoietic stem cell transplantation outcomes have significantly improved. Despite advances, aAA continues to be a challenge for hematologists. Copyright © 2018 Elsevier Inc. All rights reserved.

ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT.

PubMed

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Michallet, Mauricette; Craddock, Charles; Socié, Gerard; Volin, Lisa; Maertens, Johan A; Crawley, Charles; Blaise, Didier; Ljungman, Per T; Cornelissen, Jan; Russell, Nigel; Baron, Frédéric; Gorin, Norbert; Esteve, Jordi; Ciceri, Fabio; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

2017-08-01

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. © 2017 Wiley Periodicals, Inc.

[MMC conditioning regimen (Melphalan, MeCCNU and cyclophosphamide) followed by allogeneic peripheral blood stem cells transplantation for chronic myeloid leukemia].

PubMed

Liu, T; Jia, Y; Wang, H; Lu, Z; Meng, W; Yang, Y; Wu, J; Deng, C

1998-12-01

This paper reports 3 cases of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) for the patients with chronic myeloid leukemia (CML). The patients received MMC preparative regimen with high dose chemotherapy (Melphalan 170 mg/m2, p.o. on Day-5, MeCCNU 400 mg/m2, p.o. on Day-4, and Cyclophosphomide 60 mg/kg/day, i.v. on Days-3 and -2). The HLA-identical sibling donors received filgrastim (rhG-CSF) for mobilization at a dose of 300 micrograms/day for 6 days. Leukaphereses were done at the 6th day of mobilization. A median of 8000 ml (2 times total blood volume) of blood was processed the collecting: 2.5-4.5 x 10(8)/kg MNC, 12.8-20.0 x 10(6)/kg CD34+ cells (including 4.8-7.5 x 10(6)/kg CD34+CD33-, 8.0-13.0 x 10(6)/kg CD34+CD33+), and 3.5-4.3 x 10(5)/kg CFU-GM. Cyclosporin A and methotrexate were used for GVHD prophylaxis. Hematopoitic function recovered as for 14-20 days to > 0.5 x 10(9)/L of neutrophil count, and for 16-34 days to > 20 x 10(9)/L of platelet count. At day + 100, chromosome analysis of bone marrow cells showed that complete chimera without ph1 positive chromosome in Cases 1 and 3, and a partial chimera with 73% donor karyotype in Case 2. All patients now are in disease free survival. No episode of acute graft versus host disease (GVHD) developed. It was concluded that HLA matched sibling allogeneic PBSCT result in rapid hematopoitic reconstitution and the MMC conditioning regimen is effective both in leukemic cells eradication and in immunosuppression for stem cells engraftment, and the drug related toxicity could be tolerated by patients.

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia.

PubMed

Cavazzana-Calvo, Marina; Payen, Emmanuel; Negre, Olivier; Wang, Gary; Hehir, Kathleen; Fusil, Floriane; Down, Julian; Denaro, Maria; Brady, Troy; Westerman, Karen; Cavallesco, Resy; Gillet-Legrand, Beatrix; Caccavelli, Laure; Sgarra, Riccardo; Maouche-Chrétien, Leila; Bernaudin, Françoise; Girot, Robert; Dorazio, Ronald; Mulder, Geert-Jan; Polack, Axel; Bank, Arthur; Soulier, Jean; Larghero, Jérôme; Kabbara, Nabil; Dalle, Bruno; Gourmel, Bernard; Socie, Gérard; Chrétien, Stany; Cartier, Nathalie; Aubourg, Patrick; Fischer, Alain; Cornetta, Kenneth; Galacteros, Frédéric; Beuzard, Yves; Gluckman, Eliane; Bushman, Frederick; Hacein-Bey-Abina, Salima; Leboulch, Philippe

2010-09-16

The β-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of β-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound β(E)/β(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas. The β(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated β(E)-globin with partial instability. When this is compounded with a non-functional β(0) allele, a profound decrease in β-globin synthesis results, and approximately half of β(E)/β(0)-thalassaemia patients are transfusion-dependent. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe β(E)/β(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded β-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.

Is There Any Reason to Prefer Cord Blood Instead of Adult Donors for Hematopoietic Stem Cell Transplants?

PubMed

Beksac, Meral

2015-01-01

As cord blood (CB) enables rapid access and tolerance to HLA mismatches, a number of unrelated CB transplants have reached 30,000. Such transplant activity has been the result of international accreditation programs maintaining highly qualified cord blood units (CBUs) reaching more than 600,000 CBUs stored worldwide. Efforts to increase stem cell content or engraftment rate of the graft by ex vivo expansion, modulation by molecules such as fucose, prostaglandin E2 derivative, complement CD26 inhibitors, or CXCR4/CXCL12 axis have been able to accelerate engraftment speed and rate. Furthermore, introduction of reduced intensity conditioning protocols, better HLA matching, and recognition of the importance of HLA-C have improved CB transplants success by decreasing transplant-related mortality. CB progenitor/stem cell content has been compared with adult stem cells revealing higher long-term repopulating capacity compared to bone marrow-mesenchymal stromal cells and lesser oncogenic potential than progenitor-induced stem cells. This chapter summarizes the advantages and disadvantages of CB compared to adult stem cells within the context of stem cell biology and transplantation.

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

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

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder

Rice plants ( Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, establishedmore » an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. Lastly, we find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.« less

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

PubMed Central

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder; Ismail, Abdelbagi; Greenberg, Anthony J.; McCouch, Susan R.

2016-01-01

Rice plants (Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, established an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. We find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice. PMID:27707775

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

DOE PAGES

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder; ...

2016-10-05

Rice plants ( Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, establishedmore » an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. Lastly, we find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.« less

Matrix Elasticity of Void-Forming Hydrogels Controls Transplanted Stem Cell-Mediated Bone Formation

PubMed Central

Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T; Darnell, Max C; Desai, Rajiv; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N; Mooney, David J.

2015-01-01

The effectiveness of stem-cell therapies has been hampered by cell death and limited control over fate1. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype2–4. Stem cell behavior can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials5–7, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem-cell behaviors in situ. PMID:26366848

Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.

PubMed

Zhang, Yalin; Kim, Min Soo; Jia, Baosen; Yan, Jingqi; Zuniga-Hertz, Juan Pablo; Han, Cheng; Cai, Dongsheng

2017-08-03

It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.

Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

NASA Astrophysics Data System (ADS)

Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

2015-12-01

The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

Application of Hyperspectral Imaging to Detect Sclerotinia sclerotiorum on Oilseed Rape Stems

PubMed Central

Kong, Wenwen; Zhang, Chu; Huang, Weihao

2018-01-01

Hyperspectral imaging covering the spectral range of 384–1034 nm combined with chemometric methods was used to detect Sclerotinia sclerotiorum (SS) on oilseed rape stems by two sample sets (60 healthy and 60 infected stems for each set). Second derivative spectra and PCA loadings were used to select the optimal wavelengths. Discriminant models were built and compared to detect SS on oilseed rape stems, including partial least squares-discriminant analysis, radial basis function neural network, support vector machine and extreme learning machine. The discriminant models using full spectra and optimal wavelengths showed good performance with classification accuracies of over 80% for the calibration and prediction set. Comparing all developed models, the optimal classification accuracies of the calibration and prediction set were over 90%. The similarity of selected optimal wavelengths also indicated the feasibility of using hyperspectral imaging to detect SS on oilseed rape stems. The results indicated that hyperspectral imaging could be used as a fast, non-destructive and reliable technique to detect plant diseases on stems. PMID:29300315

Examination of factors predicting secondary students' interest in tertiary STEM education

NASA Astrophysics Data System (ADS)

Chachashvili-Bolotin, Svetlana; Milner-Bolotin, Marina; Lissitsa, Sabina

2016-02-01

Based on the Social Cognitive Career Theory (SCCT), the study aims to investigate factors that predict students' interest in pursuing science, technology, engineering, and mathematics (STEM) fields in tertiary education both in general and in relation to their gender and socio-economic background. The results of the analysis of survey responses of 2458 secondary public school students in the fifth-largest Israeli city indicate that STEM learning experience positively associates with students' interest in pursuing STEM fields in tertiary education as opposed to non-STEM fields. Moreover, studying advanced science courses at the secondary school level decreases (but does not eliminate) the gender gap and eliminates the effect of family background on students' interest in pursuing STEM fields in the future. Findings regarding outcome expectations and self-efficacy beliefs only partially support the SCCT model. Outcome expectations and self-efficacy beliefs positively correlate with students' entering tertiary education but did not differentiate between their interests in the fields of study.

Reduced hematopoietic stem cell frequency predicts outcome in acute myeloid leukemia.

PubMed

Wang, Wenwen; Stiehl, Thomas; Raffel, Simon; Hoang, Van T; Hoffmann, Isabel; Poisa-Beiro, Laura; Saeed, Borhan R; Blume, Rachel; Manta, Linda; Eckstein, Volker; Bochtler, Tilmann; Wuchter, Patrick; Essers, Marieke; Jauch, Anna; Trumpp, Andreas; Marciniak-Czochra, Anna; Ho, Anthony D; Lutz, Christoph

2017-09-01

In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse. Copyright© 2017 Ferrata Storti Foundation.

Allogeneic hematopoietic stem cell transplantation in Primary Cutaneous T Cell Lymphoma.

PubMed

Cudillo, Laura; Cerretti, Raffaella; Picardi, Alessandra; Mariotti, Benedetta; De Angelis, Gottardo; Cantonetti, Maria; Postorino, Massimiliano; Ceresoli, Eleonora; De Santis, Giovanna; Nasso, Daniela; Pisani, Francesco; Scala, Enrico; Di Piazza, Fabio; Lanti, Alessandro

2018-06-01

In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p < 0.04) and DFS (log-rank p < 0.05). Our results confirm on a long follow-up that CTCL appears particularly susceptible to the graft versus lymphoma (GVL) effect, so that allogeneic HSCT represents a possibility of cure for advanced CTCL. The timing of HSCT in the clinical course of disease remains an open issue.

Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks.

PubMed

Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

2016-06-01

Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies.

Development of water oak stump sprouts under a partial overstory

Treesearch

Emile S. Gardiner; Lisa M. Helmig

1997-01-01

A 28-year-old water oak (Quercus nigra L.) plantation was thinned from below to either 254 or 462 stems per hectare to determine the influence of a partial canopy on oak stump sprout development. Sprout clump survival, number of living sprouts in a clump, and height and DBH of the dominant sprout in a clump were measured in years l-5 and 7 after harvest. By year 7,...

Optimizing autologous cell grafts to improve stem cell gene therapy.

PubMed

Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

2016-07-01

Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Characterization of Femoral Component Initial Stability and Cortical Strain in a Reduced Stem-Length Design.

PubMed

Small, Scott R; Hensley, Sarah E; Cook, Paige L; Stevens, Rebecca A; Rogge, Renee D; Meding, John B; Berend, Michael E

2017-02-01

Short-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs. Cortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing. Femurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design. Our findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-specific embryonic stem cells derived from human SCNT blastocysts.

PubMed

Hwang, Woo Suk; Roh, Sung Il; Lee, Byeong Chun; Kang, Sung Keun; Kwon, Dae Kee; Kim, Sue; Kim, Sun Jong; Park, Sun Woo; Kwon, Hee Sun; Lee, Chang Kyu; Lee, Jung Bok; Kim, Jin Mee; Ahn, Curie; Paek, Sun Ha; Chang, Sang Sik; Koo, Jung Jin; Yoon, Hyun Soo; Hwang, Jung Hye; Hwang, Youn Young; Park, Ye Soo; Oh, Sun Kyung; Kim, Hee Sun; Park, Jong Hyuk; Moon, Shin Yong; Schatten, Gerald

2005-06-17

Patient-specific, immune-matched human embryonic stem cells (hESCs) are anticipated to be of great biomedical importance for studies of disease and development and to advance clinical deliberations regarding stem cell transplantation. Eleven hESC lines were established by somatic cell nuclear transfer (SCNT) of skin cells from patients with disease or injury into donated oocytes. These lines, nuclear transfer (NT)-hESCs, grown on human feeders from the same NT donor or from genetically unrelated individuals, were established at high rates, regardless of NT donor sex or age. NT-hESCs were pluripotent, chromosomally normal, and matched the NT patient's DNA. The major histocompatibility complex identity of each NT-hESC when compared to the patient's own showed immunological compatibility, which is important for eventual transplantation. With the generation of these NT-hESCs, evaluations of genetic and epigenetic stability can be made. Additional work remains to be done regarding the development of reliable directed differentiation and the elimination of remaining animal components. Before clinical use of these cells can occur, preclinical evidence is required to prove that transplantation of differentiated NT-hESCs can be safe, effective, and tolerated.

Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

PubMed

Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

2018-02-01

Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

Innovation in stem cell advocacy: you only get what you can measure.

PubMed

Jakimo, Alan L; Fernandez, Alan C

2011-11-01

We propose that stem cell advocacy must engage in self-analysis to determine how to be maximally effective. For this analysis, eight advocacy elements can be measured: agitation, legislation, regulation, litigation, policy development, collaboration, education and innovation. For several of these elements, we show that stem cell advocates, particularly advocates for human embryonic stem cell research, have been matched by their opponents. This demonstrates the need for combining innovation and collaboration with advocacy-oriented education. To pursue innovative and collaborative education, we propose a 'bench-to-public knowledge' model and present some preliminary observations made with this model for different stem cell types. We also propose development of a semantic web information system to be operated within Internet Cloud/Apps/Social Media. We call this system the 'Stem Cell Information Technology Accelerator Platform'. Toward its construction, we propose formation of a working group to conceive semantic web ontology for stem cell science and its clinical translation into medicine. This ontology would function as a map of the relationships between and among the various informational components comprising discourse on stem cell research and its clinical translation, and would allow various stakeholders to contribute to evolving models of that science and translation. These models could, in turn, support an innovative and collaborative approach to education in furtherance of stem cell advocacy.

Viability and neural differentiation of mesenchymal stem cells derived from the umbilical cord following perinatal asphyxia.

PubMed

Aly, H; Mohsen, L; Badrawi, N; Gabr, H; Ali, Z; Akmal, D

2012-09-01

Hypoxia-ischemia is the leading cause of neurological handicaps in newborns worldwide. Mesenchymal stem cells (MSCs) collected from fresh cord blood of asphyxiated newborns have the potential to regenerate damaged neural tissues. The aim of this study was to examine the capacity for MSCs to differentiate into neural tissue that could subsequently be used for autologous transplantation. We collected cord blood samples from full-term newborns with perinatal hypoxemia (n=27), healthy newborns (n=14) and non-hypoxic premature neonates (n=14). Mononuclear cells were separated, counted, and then analyzed by flow cytometry to assess various stem cell populations. MSCs were isolated by plastic adherence and characterized by morphology. Cells underwent immunophenotyping and trilineage differentiation potential. They were then cultured in conditions favoring neural differentiation. Neural lineage commitment was detected using immunohistochemical staining for glial fibrillary acidic protein, tubulin III and oligodendrocyte marker O4 antibodies. Mononuclear cell count and viability did not differ among the three groups of infants. Neural differentiation was best demonstrated in the cells derived from hypoxia-ischemia term neonates, of which 69% had complete and 31% had partial neural differentiation. Cells derived from preterm neonates had the least amount of neural differentiation, whereas partial differentiation was observed in only 12%. These findings support the potential utilization of umbilical cord stem cells as a source for autologous transplant in asphyxiated neonates.

Shoot atmospheric contact is of little importance to aeration of deeper portions of the wetland plant Meionectes brownii; submerged organs mainly acquire O2 from the water column or produce it endogenously in underwater photosynthesis.

PubMed

Rich, Sarah Meghan; Pedersen, Ole; Ludwig, Martha; Colmer, Timothy David

2013-01-01

Partial shoot submergence is considered less stressful than complete submergence of plants, as aerial contact allows gas exchange with the atmosphere. In situ microelectrode studies of the wetland plant Meionectes brownii showed that O(2) dynamics in the submerged stems and aquatic roots of partially submerged plants were similar to those of completely submerged plants, with internal O(2) concentrations in both organs dropping to less than 5 kPa by dawn regardless of submergence level. The anatomy at the nodes and the relationship between tissue porosity and rates of O(2) diffusion through stems were studied. Stem internodes contained aerenchyma and had mean gas space area of 17.7% per cross section, whereas nodes had 8.2%, but nodal porosity was highly variable, some nodes had very low porosity or were completely occluded (ca. 23% of nodes sampled). The cumulative effect of these low porosity nodes would have impeded internal O(2) movement down stems. Therefore, regardless of the presence of an aerial connection, the deeper portions of submerged organs sourced most of their O(2) via inwards diffusion from the water column during the night, and endogenous production in underwater photosynthesis during the daytime. © 2012 Blackwell Publishing Ltd.

Atomic bonding effects in annular dark field scanning transmission electron microscopy. II. Experiments

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

Odlyzko, Michael L.; Held, Jacob T.; Mkhoyan, K. Andre, E-mail: mkhoyan@umn.edu

2016-07-15

Quantitatively calibrated annular dark field scanning transmission electron microscopy (ADF-STEM) imaging experiments were compared to frozen phonon multislice simulations adapted to include chemical bonding effects. Having carefully matched simulation parameters to experimental conditions, a depth-dependent bonding effect was observed for high-angle ADF-STEM imaging of aluminum nitride. This result is explained by computational predictions, systematically examined in the preceding portion of this study, showing the propagation of the converged STEM beam to be highly sensitive to net interatomic charge transfer. Thus, although uncertainties in experimental conditions and simulation accuracy remain, the computationally predicted experimental bonding effect withstands the experimental testing reportedmore » here.« less

Strategy for reliable strain measurement in InAs/GaAs materials from high-resolution Z-contrast STEM images

NASA Astrophysics Data System (ADS)

Vatanparast, Maryam; Vullum, Per Erik; Nord, Magnus; Zuo, Jian-Min; Reenaas, Turid W.; Holmestad, Randi

2017-09-01

Geometric phase analysis (GPA), a fast and simple Fourier space method for strain analysis, can give useful information on accumulated strain and defect propagation in multiple layers of semiconductors, including quantum dot materials. In this work, GPA has been applied to high resolution Z-contrast scanning transmission electron microscopy (STEM) images. Strain maps determined from different g vectors of these images are compared to each other, in order to analyze and assess the GPA technique in terms of accuracy. The SmartAlign tool has been used to improve the STEM image quality getting more reliable results. Strain maps from template matching as a real space approach are compared with strain maps from GPA, and it is discussed that a real space analysis is a better approach than GPA for aberration corrected STEM images.

Therapeutic cloning in individual parkinsonian mice

PubMed Central

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

FPFH-based graph matching for 3D point cloud registration

NASA Astrophysics Data System (ADS)

Zhao, Jiapeng; Li, Chen; Tian, Lihua; Zhu, Jihua

2018-04-01

Correspondence detection is a vital step in point cloud registration and it can help getting a reliable initial alignment. In this paper, we put forward an advanced point feature-based graph matching algorithm to solve the initial alignment problem of rigid 3D point cloud registration with partial overlap. Specifically, Fast Point Feature Histograms are used to determine the initial possible correspondences firstly. Next, a new objective function is provided to make the graph matching more suitable for partially overlapping point cloud. The objective function is optimized by the simulated annealing algorithm for final group of correct correspondences. Finally, we present a novel set partitioning method which can transform the NP-hard optimization problem into a O(n3)-solvable one. Experiments on the Stanford and UWA public data sets indicates that our method can obtain better result in terms of both accuracy and time cost compared with other point cloud registration methods.

Binding ligand prediction for proteins using partial matching of local surface patches.

PubMed

Sael, Lee; Kihara, Daisuke

2010-01-01

Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

Binding Ligand Prediction for Proteins Using Partial Matching of Local Surface Patches

PubMed Central

Sael, Lee; Kihara, Daisuke

2010-01-01

Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group. PMID:21614188

Signals that regulate the oncogenic fate of neural stem cells and progenitors

PubMed Central

Swartling, Fredrik J.; Bolin, Sara; Phillips, Joanna J.; Persson, Anders I.

2013-01-01

Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors. PMID:23376224

Floods in the Iowa River basin upstream from Coralville Lake, Iowa

USGS Publications Warehouse

Heinitz, Albert J.

1973-01-01

Flood profiles for the main stem include those for the 1947, 1954, 1969, the computed 25- and 50-year floods, and a partial profile for the June 1972 flood. On the West Branch Iowa River, profiles are shown for the 1944, 1969, the computed 25- and 50-year floods, and a partial profile for the June 1954 flood. On the East Branch Iowa River, profiles are shown for the 1954, 1969, the computed 25- and 50-year floods, and a partial profile for the June 1944 flood. Low-water profiles are shown for all reaches.

NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

PubMed

Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

2012-02-01

Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

The Teacher Technology Integration Experience: Practice and Reflection in the Classroom

ERIC Educational Resources Information Center

Ruggiero, Dana; Mong, Christopher J.

2015-01-01

Previous studies indicated that the technology integration practices of teachers in the classroom often did not match their teaching styles. Researchers concluded that this was due, at least partially, to external barriers that prevented teachers from using technology in ways that matched their practiced teaching style. Many of these barriers,…

Adult Regularization of Inconsistent Input Depends on Pragmatic Factors

ERIC Educational Resources Information Center

Perfors, Amy

2016-01-01

In a variety of domains, adults who are given input that is only partially consistent do not discard the inconsistent portion (regularize) but rather maintain the probability of consistent and inconsistent portions in their behavior (probability match). This research investigates the possibility that adults probability match, at least in part,…

Impact of ABO incompatibility on patients' outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT.

PubMed

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-Jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-06-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II-IV acute graft- versus -host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22-4.66; P =0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft- versus -host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft- versus -host disease rates (HR 2.03; 95% CI: 1.00-4.10; P =0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 - 3.18; P =0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. Copyright© Ferrata Storti Foundation.

Impact of ABO incompatibility on patients’ outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT

PubMed Central

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-01-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II–IV acute graft-versus-host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22–4.66; P=0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft-versus-host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II–IV acute graft-versus-host disease rates (HR 2.03; 95% CI: 1.00–4.10; P=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 – 3.18; P=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. PMID:28255020

Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro.

PubMed

Ozaki, Masahiro; Iwanami, Akio; Nagoshi, Narihito; Kohyama, Jun; Itakura, Go; Iwai, Hiroki; Nishimura, Soraya; Nishiyama, Yuichiro; Kawabata, Soya; Sugai, Keiko; Iida, Tsuyoshi; Matsubayashi, Kohei; Isoda, Miho; Kashiwagi, Rei; Toyama, Yoshiaki; Matsumoto, Morio; Okano, Hideyuki; Nakamura, Masaya

2017-03-01

To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

ClinicalTrials.gov

2012-11-07

Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Follicular Lymphoma; Multiple Myeloma; NHL; Myeloproliferative Diseases; Chronic Myeloid Leukemia; Renal Cell Carcinoma; Aplastic Anemia

Childhood Hematopoietic Cell Transplantation (PDQ®)—Health Professional Version

Cancer.gov

Childhood hematopoietic cell transplantation involves the infusion of blood stem cells into a patient to reconstitute the blood system. Get detailed information about autologous and allogeneic transplant, HLA matching, preparative regimens, and complications in this summary for clinicians.

Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology-Oncology).

PubMed

Svahn, Johanna; Bagnasco, Francesca; Cappelli, Enrico; Onofrillo, Daniela; Caruso, Silvia; Corsolini, Fabio; De Rocco, Daniela; Savoia, Anna; Longoni, Daniela; Pillon, Marta; Marra, Nicoletta; Ramenghi, Ugo; Farruggia, Piero; Locasciulli, Anna; Addari, Carmen; Cerri, Carla; Mastrodicasa, Elena; Casazza, Gabriella; Verzegnassi, Federico; Riccardi, Francesca; Haupt, Riccardo; Barone, Angelica; Cesaro, Simone; Cugno, Chiara; Dufour, Carlo

2016-07-01

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Science and Ethics of Induced Pluripotency: What Will Become of Embryonic Stem Cells?

PubMed Central

Zacharias, David G.; Nelson, Timothy J.; Mueller, Paul S.; Hook, C. Christopher

2011-01-01

For over a decade, the field of stem cell research has advanced tremendously and gained new attention in light of novel insights and emerging developments for regenerative medicine. Invariably, multiple considerations come into play, and clinicians and researchers must weigh the benefits of certain stem cell platforms against the costs they incur. Notably, human embryonic stem (hES) cell research has been a source of continued debate, leading to differing policies and regulations worldwide. This article briefly reviews current stem cell platforms, looking specifically at the two existing pluripotent lines available for potential therapeutic applications: hES cells and induced pluripotent stem (iPS) cells. We submit iPS technology as a viable and possibly superior alternative for future medical and research endeavors as it obviates many ethical and resource-related concerns posed by hES cells while prospectively matching their potential for scientific use. However, while the clinical realities of iPS cells appear promising, we must recognize the current limitations of this technology, avoid hype, and articulate ethically acceptable medical and scientific goals. PMID:21719620

Structator: fast index-based search for RNA sequence-structure patterns

PubMed Central

2011-01-01

Background The secondary structure of RNA molecules is intimately related to their function and often more conserved than the sequence. Hence, the important task of searching databases for RNAs requires to match sequence-structure patterns. Unfortunately, current tools for this task have, in the best case, a running time that is only linear in the size of sequence databases. Furthermore, established index data structures for fast sequence matching, like suffix trees or arrays, cannot benefit from the complementarity constraints introduced by the secondary structure of RNAs. Results We present a novel method and readily applicable software for time efficient matching of RNA sequence-structure patterns in sequence databases. Our approach is based on affix arrays, a recently introduced index data structure, preprocessed from the target database. Affix arrays support bidirectional pattern search, which is required for efficiently handling the structural constraints of the pattern. Structural patterns like stem-loops can be matched inside out, such that the loop region is matched first and then the pairing bases on the boundaries are matched consecutively. This allows to exploit base pairing information for search space reduction and leads to an expected running time that is sublinear in the size of the sequence database. The incorporation of a new chaining approach in the search of RNA sequence-structure patterns enables the description of molecules folding into complex secondary structures with multiple ordered patterns. The chaining approach removes spurious matches from the set of intermediate results, in particular of patterns with little specificity. In benchmark experiments on the Rfam database, our method runs up to two orders of magnitude faster than previous methods. Conclusions The presented method's sublinear expected running time makes it well suited for RNA sequence-structure pattern matching in large sequence databases. RNA molecules containing several stem-loop substructures can be described by multiple sequence-structure patterns and their matches are efficiently handled by a novel chaining method. Beyond our algorithmic contributions, we provide with Structator a complete and robust open-source software solution for index-based search of RNA sequence-structure patterns. The Structator software is available at http://www.zbh.uni-hamburg.de/Structator. PMID:21619640

Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development

PubMed Central

Mulugeta, Yeruk; Barrett, Jeffrey S.; Nelson, Robert; Eshete, Abel Tilahun; Mushtaq, Alvina; Yao, Lynne; Glasgow, Nicole; Mulberg, Andrew E.; Gonzalez, Daniel; Green, Dionna; Florian, Jeffry; Krudys, Kevin; Seo, Shirley; Kim, Insook; Chilukuri, Dakshina; Burckart, Gilbert J.

2017-01-01

During drug development, matching adult systemic exposures of drugs is a common approach for dose selection in pediatric patients when efficacy is partially or fully extrapolated. This is a systematic review of approaches used for matching adult systemic exposures as the basis for dose selection in pediatric trials submitted to the U.S. Food and Drug Administration (FDA) between 1998 and 2012. The trial design of pediatric pharmacokinetic (PK) studies and the pediatric and adult systemic exposure data were obtained from FDA publicly available databases containing reviews of pediatric trials. Exposure matching approaches that were used as the basis for pediatric dose selection were reviewed. The PK data from the adult and pediatric populations were used to quantify exposure agreement between the two patient populations. The main measures were the pediatric PK studies trial design elements and drug systemic exposures (adult and pediatric). There were 31 products (86 trials) with full or partial extrapolation of efficacy with an available PK assessment. Pediatric exposures had a range of mean Cmax and AUC ratios (pediatric/adult) of 0.63-4.19 and 0.36-3.60 respectively. Seven of the 86 trials (8.1%) had a pre-defined acceptance boundary used to match adult exposures. The key PK parameter was consistently predefined for antiviral and anti-infective products. Approaches to match exposure in children and adults varied across products. A consistent approach for systemic exposure matching and evaluating pediatric PK studies is needed to guide future pediatric trials. PMID:27040726

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice.

PubMed

Wang, Diane R; Wolfrum, Edward J; Virk, Parminder; Ismail, Abdelbagi; Greenberg, Anthony J; McCouch, Susan R

2016-11-01

Rice plants (Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, established an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. We find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Sapwood development in Pinus radiata trees grown for three years at ambient and elevated carbon dioxide partial pressures.

PubMed

Atwell, B J; Henery, M L; Whitehead, D

2003-01-01

Clonal trees of Pinus radiata D. Don were grown in open-top chambers at a field site in New Zealand for 3 years at ambient (37 Pa) or elevated (65 Pa) carbon dioxide (CO2) partial pressure. Nitrogen (N) was supplied to half of the trees in each CO2 treatment, at 15 g N m-2 in the first year and 60 g N m-2 in the subsequent 2 years (high-N treatment). Trees in the low-N treatment were not supplied with N but received the same amount of other nutrients as trees in the high-N treatment. In the first year, stem basal area increased more in trees growing at elevated CO2 partial pressure and high-N supply than in control trees, suggesting a positive interaction between these resources. However, the relative rate of growth became the same across trees in all treatments after 450 days, resulting in trees growing at elevated CO2 partial pressure and high-N supply having larger basal areas than trees in the other treatments. Sapwood N content per unit dry mass was consistently about 0.09% in all treatments, indicating that N status was not suppressed by elevated CO2 partial pressure. Thus, during the first year of growth, an elevated CO2 partial pressure enhanced carbon (C) and N storage in woody stems, but there was no further stimulus to C and N deposition after the first year. The chemical composition of sapwood was unaffected by elevated CO2 partial pressure, indicating that no additional C was sequestered through lignification. However, independent of the treatments, early wood was 13% richer in lignin than late wood. Elevated CO2 partial pressure decreased the proportion of sapwood occupied by the lumina of tracheids by up to 12%, indicating increased sapwood density in response to CO2 enrichment. This effect was probably a result of thicker tracheid walls rather than narrower lumina.

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.

PubMed

Shan, Xiaoyin; Roberts, Cleresa; Kim, Eun Ji; Brenner, Ariana; Grant, Gregory; Percec, Ivona

2017-05-01

Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASCs), is increasingly recognized, the study of chronological aging in ASCs is technically difficult and remains poorly understood. Here, we use our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase. Our results reveal novel chronological aging mechanisms in ASCs that are inherently different from differentiated cells and that may reflect an organismal attempt to meet the increased demands of tissue and organ homeostasis during aging. Stem Cells 2017;35:1392-1401. © 2017 AlphaMed Press.

A network of heterochronic genes including Imp1 regulates temporal changes in stem cell properties

PubMed Central

Nishino, Jinsuke; Kim, Sunjung; Zhu, Yuan; Zhu, Hao; Morrison, Sean J

2013-01-01

Stem cell properties change over time to match the changing growth and regeneration demands of tissues. We showed previously that adult forebrain stem cell function declines during aging because of increased expression of let-7 microRNAs, evolutionarily conserved heterochronic genes that reduce HMGA2 expression. Here we asked whether let-7 targets also regulate changes between fetal and adult stem cells. We found a second let-7 target, the RNA binding protein IMP1, that is expressed by fetal, but not adult, neural stem cells. IMP1 expression was promoted by Wnt signaling and Lin28a expression and opposed by let-7 microRNAs. Imp1-deficient neural stem cells were prematurely depleted in the dorsal telencephalon due to accelerated differentiation, impairing pallial expansion. IMP1 post-transcriptionally inhibited the expression of differentiation-associated genes while promoting the expression of self-renewal genes, including Hmga2. A network of heterochronic gene products including Lin28a, let-7, IMP1, and HMGA2 thus regulates temporal changes in stem cell properties. DOI: http://dx.doi.org/10.7554/eLife.00924.001 PMID:24192035

Generation, recognition, and consistent fusion of partial boundary representations from range images

NASA Astrophysics Data System (ADS)

Kohlhepp, Peter; Hanczak, Andrzej M.; Li, Gang

1994-10-01

This paper presents SOMBRERO, a new system for recognizing and locating 3D, rigid, non- moving objects from range data. The objects may be polyhedral or curved, partially occluding, touching or lying flush with each other. For data collection, we employ 2D time- of-flight laser scanners mounted to a moving gantry robot. By combining sensor and robot coordinates, we obtain 3D cartesian coordinates. Boundary representations (Brep's) provide view independent geometry models that are both efficiently recognizable and derivable automatically from sensor data. SOMBRERO's methods for generating, matching and fusing Brep's are highly synergetic. A split-and-merge segmentation algorithm with dynamic triangular builds a partial (21/2D) Brep from scattered data. The recognition module matches this scene description with a model database and outputs recognized objects, their positions and orientations, and possibly surfaces corresponding to unknown objects. We present preliminary results in scene segmentation and recognition. Partial Brep's corresponding to different range sensors or viewpoints can be merged into a consistent, complete and irredundant 3D object or scene model. This fusion algorithm itself uses the recognition and segmentation methods.

MHC-matched induced pluripotent stem cells can attenuate cellular and humoral immune responses but are still susceptible to innate immunity in pigs.

PubMed

Mizukami, Yoshihisa; Abe, Tomoyuki; Shibata, Hiroaki; Makimura, Yukitoshi; Fujishiro, Shuh-hei; Yanase, Kimihide; Hishikawa, Shuji; Kobayashi, Eiji; Hanazono, Yutaka

2014-01-01

Recent studies have revealed negligible immunogenicity of induced pluripotent stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human iPS cells would not elicit immune responses in the autologous setting. However, given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would likely be used for medical applications, a more faithful model system is needed to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS cells were generated from the SLA-defined C1 strain of Clawn miniature swine, which were confirmed to develop teratomas in mice, and transplanted into the testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on 47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T-cell responses to the transplanted MHC-matched (C1) iPS cells were significantly lower compared to allogeneic cells. The humoral immune responses were also attenuated in the C1-to-C1 setting. More importantly, even MHC-matched iPS cells were susceptible to innate immunity, NK cells and serum complement. iPS cells lacked the expression of SLA class I and sialic acids. The in vitro cytotoxic assay showed that C1 iPS cells were targeted by NK cells and serum complement of C1. In vivo, the C1 iPS cells developed larger teratomas in NK-deficient NOG (T-B-NK-) mice (n = 10) than in NK-competent NOD/SCID (T-B-NK+) mice (n = 8) (p<0.01). In addition, C1 iPS cell failed to form teratomas after incubation with the porcine complement-active serum. Taken together, MHC-matched iPS cells can attenuate cellular and humoral immune responses, but still susceptible to innate immunity in pigs.

Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

PubMed

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

Variability in Prefrontal Hemodynamic Response during Exposure to Repeated Self-Selected Music Excerpts, a Near-Infrared Spectroscopy Study

PubMed Central

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes. PMID:25837268

Human umbilical cord blood stem cells show PDGF-D–dependent glioma cell tropism in vitro and in vivo

PubMed Central

Gondi, Christopher S.; Veeravalli, Krishna Kumar; Gorantla, Bharathi; Dinh, Dzung H.; Fassett, Dan; Klopfenstein, Jeffrey D.; Gujrati, Meena; Rao, Jasti S.

2010-01-01

Despite advances in clinical therapies and technologies, the prognosis for patients with malignant glioma is poor. Neural stem cells (NSCs) have a chemotactic tropism toward glioma cells. The use of NSCs as carriers of therapeutic agents for gliomas is currently being explored. Here, we demonstrate that cells isolated from the umbilical cord blood show mesenchymal characteristics and can differentiate to adipocytes, osteocytes, and neural cells and show tropism toward cancer cells. We also show that these stem cells derived from the human umbilical cord blood (hUCB) induce apoptosis-like cell death in the glioma cell line SNB19 via Fas-mediated caspase-8 activation. From our glioma tropism studies, we have observed that hUCB cells show tropism toward glioma cells in vitro, in vivo, and ex vivo. We determined that this migration is partially dependent on the expression levels of platelet-derived growth factor (PDGF)-D from glioma cells and have observed that local concentration gradient of PDGF-D is sufficient to cause migration of hUCB cells toward the gradient as seen from our brain slice cultures. In our animal experiment studies, we observed that intracranially implanted SNB19 green fluorescent protein cells induced tropism of the hUCB cells toward themselves. In addition, the ability of these hUCBs to inhibit established intracranial tumors was also observed. We also determined that the migration of stem cells toward glioma cells was partially dependent on PDGF secreted by glioma cells and that the presence of PDGF-receptor (PDGFR) on hUCB is required for migration. Our results demonstrate that hUCB are capable of inducing apoptosis in human glioma cells and also show that glioma tropism and hUCB tropism toward glioma cells are partially dependent on the PDGF/PGGFR system. PMID:20406896

Preparation of Underrepresented Males for Scientific Careers: A Study of the Dr. John H. Hopps Jr. Defense Research Scholars Program at Morehouse College

PubMed Central

Thompson, Rahmelle C.; Monroe-White, Thema; Xavier, Jeffrey; Howell, Courtney; Moore, Myisha Roberson; Haynes, J. K.

2016-01-01

Equal representation within higher education science, technology, engineering, and mathematics (STEM) fields and the STEM workforce in the United States across demographically diverse populations is a long-standing challenge. This study uses two-to-one nearest-neighbor matched-comparison group design to examine academic achievement, pursuit of graduate science degree, and classification of graduate institution attended by students participating in the Hopps Scholars Program (Hopps) at Morehouse College. Hopps is a highly structured enrichment program aimed at increasing participation of black males in STEM fields. Morehouse institutional records, Hopps Program records, and National Student Clearinghouse data were used to examine differences between Hopps and non-Hopps STEM graduates of Morehouse. Two-way sample t tests and chi-square tests revealed significant differences in academic achievement, likelihood of STEM degree pursuit, and the classification of graduate institutions attended by Hopps versus non-Hopps students. Hopps Scholars were significantly more likely than non-Hopps STEM graduates both to pursue STEM doctoral degrees and to attend doctoral-granting institutions with higher research activity. The Hopps Program’s approach to training black male students for scientific careers is a model of success for other programs committed to increasing the number of black males pursuing advanced degrees in STEM. PMID:27562959

Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study.

PubMed

Tanagho, Youssef S; Bhayani, Sam B; Sandhu, Gurdarshan S; Vaughn, Nicholas P; Nepple, Kenneth G; Figenshau, R Sherburne

2012-10-01

To evaluate the potential benefit of performing off-clamp robot-assisted partial nephrectomy as it relates to renal functional outcomes, while assessing the safety profile of this unconventional surgical approach. Twenty-nine patients who underwent off-clamp robot-assisted partial nephrectomy for suspected renal cell carcinoma at Washington University between March 2008 and September 2011 (group 1) were matched to 29 patients with identical nephrometry scores and comparable baseline renal function who underwent robot-assisted partial nephrectomy with hilar clamping during the same period (group 2). The matched cohorts' perioperative and renal functional outcomes were compared at a mean 9-month follow-up. Mean estimated blood loss was 146.4 mL in group 1, versus 103.9 mL in group 2 (P = .039). Mean hilar clamp time was 0 minutes in group 1 and 14.7 minutes in group 2. No perioperative complications were encountered in group 1; 1 Clavien-2 complication (3.4%) occurred in group 2 (P = 1.000). At 9-month follow-up, mean estimated glomerular filtration rate in group 1 was 79.9 versus 84.8 mL/min/1.73 m(2) preoperatively (P = .013); mean estimated glomerular filtration rate in group 2 was 74.1 versus 85.8 mL/min/1.73 m(2) preoperatively (P < .001). Hence, estimated glomerular filtration rate declined by a mean of 4.9 mL/min/1.73 m(2) in group 1 versus 11.7 mL/min/1.73 m(2) in group 2 (P = .033). Off-clamp robot-assisted partial nephrectomy is associated with a favorable morbidity profile and relatively greater renal functional preservation compared to clamped robot-assisted partial nephrectomy. Nevertheless, the benefit is small in renal functional terms and may have very limited clinical relevance. Copyright © 2012 Elsevier Inc. All rights reserved.

Using ClinicalTrials.gov to supplement information in ophthalmology conference abstracts about trial outcomes: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching "new" outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned.

Morphological priming by itself: a study of Portuguese conjugations.

PubMed

Veríssimo, João; Clahsen, Harald

2009-07-01

Does the language processing system make use of abstract grammatical categories and representations that are not directly visible from the surface form of a linguistic expression? This study examines stem-formation processes and conjugation classes, a case of 'pure' morphology that provides insight into the role of grammatical structure in language processing. We report results from a cross-modal priming experiment examining 1st and 3rd conjugation verb forms in Portuguese. Although items were closely matched with respect to a range of non-morphological factors, distinct priming patterns were found for 1st and 3rd conjugation stems. We attribute the observed priming patterns to different representations of conjugational stems, combinatorial morphologically structured ones for 1st conjugation and un-analyzed morphologically unstructured ones for 3rd conjugation stems. Our findings underline the importance of morphology for language comprehension indicating that morphological analysis goes beyond the identification of grammatical morphemes.

Ceramic Heads Decrease Metal Release Caused by Head-taper Fretting and Corrosion.

PubMed

Kocagoz, Sevi B; Underwood, Richard J; MacDonald, Daniel W; Gilbert, Jeremy L; Kurtz, Steven M

2016-04-01

Metal release resulting from taper fretting and corrosion is a clinical concern, because wear and corrosion products may stimulate adverse local tissue reactions. Unimodular hip arthroplasties have a conical taper between the femoral head (head bore taper) and the femoral stem (stem cone taper). The use of ceramic heads has been suggested as a way of reducing the generation of wear and corrosion products from the head bore/stem cone taper junction. A previous semiquantitative study found that ceramic heads had less visual evidence of fretting-corrosion damage compared with CoCr heads; but, to our knowledge, no studies have quantified the volumetric material loss from the head bore and stem cone tapers of a matched cohort of ceramic and metal heads. We asked: (1) Do ceramic heads result in less volume of material loss at the head-stem junction compared with CoCr heads; (2) do stem cone tapers have less volumetric material loss compared with CoCr head bore tapers; (3) do visual fretting-corrosion scores correlate with volumetric material loss; and (4) are device, patient, or intraoperative factors associated with volumetric material loss? A quantitative method was developed to estimate volumetric material loss from the head and stem taper in previously matched cohorts of 50 ceramic and 50 CoCr head-stem pairs retrieved during revision surgery for causes not related to adverse reactions to metal particles. The cohorts were matched according to (1) implantation time, (2) stem flexural rigidity, and (3) lateral offset. Fretting corrosion was assessed visually using a previously published four-point, semiquantitative scoring system. The volumetric loss was measured using a precision roundness machine. Using 24 equally spaced axial traces, the volumetric loss was estimated using a linear least squares fit to interpolate the as-manufactured surfaces. The results of this analysis were considered in the context of device (taper angle clearance, head size, head offset, lateral offset, stem material, and stem surface finish) and patient factors that were obtained from the patients' operative records (implantation time, age at insertion, activity level, and BMI). The cumulative volumetric material losses estimated for the ceramic cohort had a median of 0.0 mm(3) per year (range, 0.0-0.4 mm(3)). The cumulative volumetric material losses estimated for the CoCr cohort had a median of 0.1 mm(3) per year (range, 0.0-8.8 mm(3)). An order of magnitude reduction in volumetric material loss was found when a ceramic head was used instead of a CoCr head (p < 0.0001). In the CoCr cohort, the femoral head bore tapers had a median material loss of 0.02 mm(3) (range, 0.0-8.7 mm(3)) and the stem cone tapers had a median material loss of 0.0 mm(3) (range, 0.0-0.32 mm(3)/year). There was greater material loss from femoral head bore tapers compared with stem cone tapers in the CoCr cohort (p < 0.001). There was a positive correlation between visual scoring and volumetric material loss (Spearman's ρ = 0.67, p < 0.01). Although visual scoring was effective for preliminary screening to separate tapers with no or mild damage from tapers with moderate to severe damage, it was not capable of discriminating in the large range of material loss observed at the taper surfaces with moderate to severe fretting-corrosion damage, indicated with a score of 3 or 4. We observed no correlations between volumetric material loss and device and patient factors. The majority of estimated material loss from the head bore-stem cone junctions resulting from taper fretting and corrosion was from the CoCr head bore tapers as opposed to the stem cone tapers. Additionally, the total material loss from the ceramic cohort showed a reduction in the amount of metal released by an order of magnitude compared with the CoCr cohort. We found that ceramic femoral heads may be an effective means by which to reduce metal release caused by taper fretting and corrosion at the head bore-stem cone modular interface in THAs.

Brain-stem laceration and blunt rupture of thoracic aorta: is the intrapleural bleeding postmortem in origin?: an autopsy study.

PubMed

Zivković, Vladimir; Nikolić, Slobodan; Babić, Dragan; Juković, Fehim

2011-12-01

Some of the fatally injured car occupants could have had both blunt rupture of thoracic aorta with great amount of intrapleural blood, and pontomedullar laceration of brain-stem as well, with both injuries being fatal. The aim of this study was to answer if all intrapleural bleeding in these cases was antemortem, or the bleeding could also be partially postmortem. We observed the group of 66 cases of blunt aortic rupture: 21 case with brain-stem laceration, and 45 cases without it. The average amount of intrapleural bleeding in cases without brain-stem laceration (1993 ± 831 mL) was significantly higher than in those with this injury (1100 ± 708 mL) (t = 4.252, df = 64, P = 0.000). According to our results, in cases of the thoracic aorta rupture with concomitant brain-stem laceration, the amount of intrapleural bleeding less than 1500 mL, should be considered mostly as postmortem in origin, and in such cases, only the brain-stem injury should be considered as cause of death.

An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

PubMed

Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

2017-06-01

Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia

PubMed Central

Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D.; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A.; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D. Wade; Yang, Feng-Chun

2017-01-01

Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. PMID:28341737

Starch and the Control of Kernel Number in Maize at Low Water Potentials1

PubMed Central

Zinselmeier, Christopher; Jeong, Byeong-Ryong; Boyer, John S.

1999-01-01

After reproduction is initiated in plants, subsequent reproductive development is sometimes interrupted, which decreases the final number of seeds and fruits. We subjected maize (Zea mays L.) to low water potentials (ψw) that frequently cause this kind of failure. We observed metabolite pools and enzyme activities in the developing ovaries while we manipulated the sugar stream by feeding sucrose (Suc) to the stems. Low ψw imposed for 5 d around pollination allowed embryos to form, but abortion occurred and kernel number decreased markedly. The ovary contained starch that nearly disappeared during this abortion. Analyses showed that all of the intermediates in starch synthesis were depleted. However, when labeled Suc was fed to the stems, label arrived at the ovaries. Solute accumulated and caused osmotic adjustment. Suc accumulated, but other intermediates did not, showing that a partial block in starch synthesis occurred at the first step in Suc utilization. This step was mediated by invertase, which had low activity. Because of the block, Suc feeding only partially prevented starch disappearance and abortion. These results indicate that young embryos abort when the sugar stream is interrupted sufficiently to deplete starch during early ovary development, and this abortion results in a loss of mature seeds and fruits. At low ψw, maintaining the sugar stream partially prevented the abortion, but invertase regulated the synthesis of ovary starch and partially prevented full recovery. PMID:10482657

Redox environment in stem and differentiated cells: A quantitative approach.

PubMed

Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

2017-08-01

Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Acute myeloid leukemia developing in a granulocyte colony-stimulating factor-mobilized stem cell donor: A case report and review of the literature.

PubMed

Haddad, Housam; Wungjiranirun, Manida; Gergis, Usama

2016-09-01

We describe the first case of a FLT-3 mutated AML in a healthy donor, 3years after recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cell (PBSC) harvest. The patient had a myeloablative (MA) matched unrelated donor (MUD) stem cell transplant (SCT) for refractory AML. However, he experienced a secondary graft failure. He had a second non myeloablative (NMA) on day +75 from a second MUD. He achieved a complete neutrophil and platelet engraftment. After 4years of follow up, he is alive in complete remission with full second donor chimerism. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Rare complications after second hematopoietic stem cell transplantation for thalassemia major.

PubMed

Yanir, Asaf; Yatsiv, Ido; Braun, Jacques; Zilkha, Amir; Brooks, Rebecca; Bouhanna, Dalia; Weintraub, Michael; Stepensky, Polina

2012-07-01

We describe an 11-year-old girl with thalassemia major who underwent a second hematopoietic stem cell transplantation from a matched related donor and who subsequently developed posttransplant lymphoproliferative disorder complicated by severe ascending paralysis resembling Guillian-Barré syndrome. Six months later she developed a massive pericardial effusion. She received a multimodal treatment for these complications and currently, 18 months after transplantation, she is in a good clinical condition, is transfusion independent, with no evidence of graft-versus-host disease and off all treatment. This case highlights the dilemma surrounding second hematopoietic stem cell transplantations in hemoglobinopathies and the need for a careful, well informed, and collaborative decision-making process by patients, families, and medical professionals.

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease.

PubMed

Singbrant, Sofie; Wall, Meaghan; Moody, Jennifer; Karlsson, Göran; Chalk, Alistair M; Liddicoat, Brian; Russell, Megan R; Walkley, Carl R; Karlsson, Stefan

2014-04-01

The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. However, its operative relevance in these cells remains elusive. We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compartments, and a marked enhancement of myeloid differentiation at the expense of other lineages. Accordingly, enforced expression of SKI induced a gene signature associated with hematopoietic stem cells and myeloid differentiation, as well as hepatocyte growth factor signaling. Here we demonstrate that, in contrast to what has generally been assumed, the significant impact of SKI on hematopoiesis is independent of its ability to inhibit TGF-beta signaling. Instead, myeloid progenitors expressing SKI are partially dependent on functional hepatocyte growth factor signaling. Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease.

Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

PubMed Central

Zheng, Junke; Lu, Zhigang; Kocabas, Fatih; Böttcher, Ralph T.; Costell, Mercedes; Kang, Xunlei; Liu, Xiaoye; DeBerardinis, Ralph J.; Wang, Qianming; Chen, Guo-Qiang

2014-01-01

How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-l-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow. PMID:24385538

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease

PubMed Central

Singbrant, Sofie; Wall, Meaghan; Moody, Jennifer; Karlsson, Göran; Chalk, Alistair M.; Liddicoat, Brian; Russell, Megan R.; Walkley, Carl R.; Karlsson, Stefan

2014-01-01

The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. However, its operative relevance in these cells remains elusive. We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compartments, and a marked enhancement of myeloid differentiation at the expense of other lineages. Accordingly, enforced expression of SKI induced a gene signature associated with hematopoietic stem cells and myeloid differentiation, as well as hepatocyte growth factor signaling. Here we demonstrate that, in contrast to what has generally been assumed, the significant impact of SKI on hematopoiesis is independent of its ability to inhibit TGF-beta signaling. Instead, myeloid progenitors expressing SKI are partially dependent on functional hepatocyte growth factor signaling. Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease. PMID:24415629

Processing oscillatory signals by incoherent feedforward loops

NASA Astrophysics Data System (ADS)

Zhang, Carolyn; Wu, Feilun; Tsoi, Ryan; Shats, Igor; You, Lingchong

From the timing of amoeba development to the maintenance of stem cell pluripotency,many biological signaling pathways exhibit the ability to differentiate between pulsatile and sustained signals in the regulation of downstream gene expression.While networks underlying this signal decoding are diverse,many are built around a common motif, the incoherent feedforward loop (IFFL),where an input simultaneously activates an output and an inhibitor of the output.With appropriate parameters,this motif can generate temporal adaptation,where the system is desensitized to a sustained input.This property serves as the foundation for distinguishing signals with varying temporal profiles.Here,we use quantitative modeling to examine another property of IFFLs,the ability to process oscillatory signals.Our results indicate that the system's ability to translate pulsatile dynamics is limited by two constraints.The kinetics of IFFL components dictate the input range for which the network can decode pulsatile dynamics.In addition,a match between the network parameters and signal characteristics is required for optimal ``counting''.We elucidate one potential mechanism by which information processing occurs in natural networks with implications in the design of synthetic gene circuits for this purpose. This work was partially supported by the National Science Foundation Graduate Research Fellowship (CZ).

Sound absorption of microperforated panels inside compact acoustic enclosures

NASA Astrophysics Data System (ADS)

Yang, Cheng; Cheng, Li

2016-01-01

This paper investigates the sound absorption effect of microperforated panels (MPPs) in small-scale enclosures, an effort stemming from the recent interests in using MPPs for noise control in compact mechanical systems. Two typical MPP backing cavity configurations (an empty backing cavity and a honeycomb backing structure) are studied. Although both configurations provide basically the same sound absorption curves from standard impedance tube measurements, their in situ sound absorption properties, when placed inside a small enclosure, are drastically different. This phenomenon is explained using a simple system model based on modal analyses. It is shown that the accurate prediction of the in situ sound absorption of the MPPs inside compact acoustic enclosures requires meticulous consideration of the configuration of the backing cavity and its coupling with the enclosure in front. The MPP structure should be treated as part of the entire system, rather than an absorption boundary characterized by the surface impedance, calculated or measured in simple acoustic environment. Considering the spatial matching between the acoustic fields across the MPP, the possibility of attenuating particular enclosure resonances by partially covering the enclosure wall with a properly designed MPP structure is also demonstrated.

Bioceramic inlays do not improve mechanical incorporation of grit-blasted titanium stems in the proximal sheep femur.

PubMed

Keränen, Pauli; Koort, Jyri; Itälä, Ari; Ylänen, Heimo; Dalstra, Michel; Hupa, Mikko; Kommonen, Bertel; Aro, Hannu T

2010-03-15

The aim of the present study was to determine, if bioactive glass (BG) surface inlays improve osseointegration of titanium implants in the proximal femur of adult sheep. In simulation of uncemented primary stems (nine animals), only the proximal part of the implants was grit-blasted and three surface slots of the grit-blasted region were filled with sintered BG microspheres. Primary stems were implanted using press-fit technique. In revision stem simulation (eight animals), grit-blasting was extended over the whole implant and seven perforating holes of the stem were filled by sintered BG granules. Revision stems were implanted with a mixture of autogenous bone graft and BG granules. Comparison with solid partially or fully grit-blasted control stems implanted in the contralateral femurs was performed in the primary and revision stem experiments at 12 and 25 weeks, respectively. Implant incorporation was evaluated by torsional failure testing and histomorphometry. Only one-third of the primary stems anchored mechanically to bone. The revision stems incorporated better and the BG inlays of the revision stems showed ingrowth of new bone. However, there were no significant differences in the torsional failure loads between the stems with BG inlays and the control stems. In conclusion, surface BG inlays gave no measurable advantage in mechanical incorporation of grit-blasted titanium implants. Overall, the proximal sheep femur, characterized by minimal amount of cancellous bone and the presence of adipocytic bone marrow, seemed to present compromised bone healing conditions. (c) 2009 Wiley Periodicals, Inc.

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

PubMed

Lee, Sang Chul; Kim, Kee-Hwan; Kim, Ok-Hee; Lee, Sang Kuon; Hong, Ha-Eun; Won, Seong Su; Jeon, Sang-Jin; Choi, Byung Jo; Jeong, Wonjun; Kim, Say-June

2017-08-03

A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO 2 ) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined. We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO 2 (21%, 10%, 5%, and 1%). Subsequently, partially hepatectomized mice were injected with the secretome of ASCs cultured under different pO 2 , and then sera and liver specimens were obtained for analyses. Of all AML12 cells cultured under different pO 2 , the AML12 cells cultured under 1% pO 2 showed the highest mRNA expression of proliferation-associated markers (IL-6, HGF, and VEGF). In the cell proliferation assay, the AML12 cells cultured with the secretome of 1% pO 2 showed the highest cell proliferation, followed by the cells cultured with the secretome of 21%, 10%, and 5% pO 2 , in that order. When injected into the partially hepatectomized mice, the 1% pO 2 secretome most significantly increased the number of Ki67-positive cells, reduced serum levels of proinflammatory mediators (IL-6 and TNF-α), and reduced serum levels of liver transaminases. In addition, analysis of the liver specimens indicated that injection with the 1% pO 2 secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration. The data of this study suggest that the secretome of ASCs cultured under 1% pO 2 has the highest liver reparative and regenerative potential of all the secretomes tested here.

Double versus single high-dose melphalan 200 mg/m2 and autologous stem cell transplantation for multiple myeloma: a region-based study in 484 patients from the Nordic area

PubMed Central

Björkstrand, Bo; Klausen, Tobias W.; Remes, Kari; Gruber, Astrid; Knudsen, Lene M.; Bergmann, Olav J.; Lenhoff, Stig; Johnsen, Hans E.

2009-01-01

Autologous stem cell transplantation is still considered the standard of care in young patients with multiple myeloma (MM). This disease is the most common indication for high-dose therapy (HDT) supported by hematopoietic stem cell transplantation and much data support the benefit of this procedure. Results of randomized studies are in favor of tandem autologous transplantation although the effect on overall survival is unclear. Based on sequential registration trials in the Nordic area, we aimed to evaluate the outcome of conventional single or double HDT. During 1994–2000 we registered a total of 484 previously untreated patients under the age of 60 years at diagnosis who on a regional basis initially were treated with single [Trial NMSG #5/94 and #7/98 (N=383)] or double [Trial Huddinge Karolinska Turku Herlev (N=101)] high-dose melphalan (200 mg/m2) therapy supported by autologous stem cell transplantation. A complete or very good partial response was achieved by 40% of patients in the single transplant group and 60% of patients in the double transplant group (p=0.0006). The probability of surviving progression free for five years after the diagnosis was 25% (95% CL 18–32%) in the singletransplant group and 46% (95% CL 33–55%) in the double transplant group (p=0.0014). The estimated overall five-year survival rate was 60% in the single transplant group and 64% in the doubletransplant (p=0.9). In a multivariate analysis of variables, including single versus double transplantation, β2 microglobulin level, age, sex and disease stage, only β2 microglobulin level was predictive for overall survival (p>0.0001) and progression free survival (p=0.001). In accordance with these results, a 1:1 case-control matched comparison between double and single transplantation did not identify significant differences in overall and progression free survival. In this retrospective analysis up front double transplantation with melphalan (200 mg/m2) as compared to single transplantation did not seem to improve the final outcome among patients in the Nordic area. These data are in accordance with recent publications from the Bologna 96 trial indicating that a second transplant should not be recommended up front as standard care.

Stem Cell Ophthalmology Treatment Study II

ClinicalTrials.gov

2018-02-01

Retinal Disease; Age-Related Macular Degeneration; Retinitis Pigmentosa; Stargardt Disease; Optic Neuropathy; Nonarteritic Ischemic Optic Neuropathy; Optic Atrophy; Optic Nerve Disease; Glaucoma; Leber Hereditary Optic Neuropathy; Blindness; Vision Loss Night; Vision Loss Partial; Vision, Low; Retinopathy; Maculopathy; Macular Degeneration; Retina Atrophy

A Study of Reverse-Worded Matched Item Pairs Using the Generalized Partial Credit and Nominal Response Models

ERIC Educational Resources Information Center

Matlock Cole, Ki Lynn; Turner, Ronna C.; Gitchel, W. Dent

2018-01-01

The generalized partial credit model (GPCM) is often used for polytomous data; however, the nominal response model (NRM) allows for the investigation of how adjacent categories may discriminate differently when items are positively or negatively worded. Ten items from three different self-reported scales were used (anxiety, depression, and…

Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

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

Shi, Wen-Zhu; Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853; Miao, Yu-Liang

Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation ofmore » hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.« less

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

PubMed Central

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers.

PubMed

Wang, Ming-Te; Degol, Jessica; Ye, Feifei

2015-01-01

Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students' motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women's underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices.

Math achievement is important, but task values are critical, too: examining the intellectual and motivational factors leading to gender disparities in STEM careers

PubMed Central

Wang, Ming-Te; Degol, Jessica; Ye, Feifei

2015-01-01

Although young women now obtain higher course grades in math than boys and are just as likely to be enrolled in advanced math courses in high school, females continue to be underrepresented in some Science, Technology, Engineering, and Mathematics (STEM) occupations. This study drew on expectancy-value theory to assess (1) which intellectual and motivational factors in high school predict gender differences in career choices and (2) whether students’ motivational beliefs mediated the pathway of gender on STEM career via math achievement by using a national longitudinal sample in the United States. We found that math achievement in 12th grade mediated the association between gender and attainment of a STEM career by the early to mid-thirties. However, math achievement was not the only factor distinguishing gender differences in STEM occupations. Even though math achievement explained career differences between men and women, math task value partially explained the gender differences in STEM career attainment that were attributed to math achievement. The identification of potential factors of women’s underrepresentation in STEM will enhance our ability to design intervention programs that are optimally tailored to female needs to impact STEM achievement and occupational choices. PMID:25741292

The bachelor's to Ph.D. STEM pipeline no longer leaks more women than men: a 30-year analysis.

PubMed

Miller, David I; Wai, Jonathan

2015-01-01

For decades, research and public discourse about gender and science have often assumed that women are more likely than men to "leak" from the science pipeline at multiple points after entering college. We used retrospective longitudinal methods to investigate how accurately this "leaky pipeline" metaphor has described the bachelor's to Ph.D. transition in science, technology, engineering, and mathematics (STEM) fields in the U.S. since the 1970s. Among STEM bachelor's degree earners in the 1970s and 1980s, women were less likely than men to later earn a STEM Ph.D. However, this gender difference closed in the 1990s. Qualitatively similar trends were found across STEM disciplines. The leaky pipeline metaphor therefore partially explains historical gender differences in the U.S., but no longer describes current gender differences in the bachelor's to Ph.D. transition in STEM. The results help constrain theories about women's underrepresentation in STEM. Overall, these results point to the need to understand gender differences at the bachelor's level and below to understand women's representation in STEM at the Ph.D. level and above. Consistent with trends at the bachelor's level, women's representation at the Ph.D. level has been recently declining for the first time in over 40 years.

Induced pluripotent stem cell-based therapy for age-related macular degeneration.

PubMed

Bracha, Peter; Moore, Nicholas A; Ciulla, Thomas A

2017-09-01

In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor.  Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells.  Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive.  Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression.

Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium

PubMed Central

2013-01-01

Introduction Early pregnancy has a strong protective effect against breast cancer in humans and rodents, but the underlying mechanism is unknown. Because breast cancers are thought to arise from specific cell subpopulations of mammary epithelia, we studied the effect of parity on the transcriptome and the differentiation/proliferation potential of specific luminal and basal mammary cells in mice. Methods Mammary epithelial cell subpopulations (luminal Sca1-, luminal Sca1+, basal stem/progenitor, and basal myoepithelial cells) were isolated by flow cytometry from parous and age-matched virgin mice and examined by using a combination of unbiased genomics, bioinformatics, in vitro colony formation, and in vivo limiting dilution transplantation assays. Specific findings were further investigated with immunohistochemistry in entire glands of parous and age-matched virgin mice. Results Transcriptome analysis revealed an upregulation of differentiation genes and a marked decrease in the Wnt/Notch signaling ratio in basal stem/progenitor cells of parous mice. Separate bioinformatics analyses showed reduced activity for the canonical Wnt transcription factor LEF1/TCF7 and increased activity for the Wnt repressor TCF3. This finding was specific for basal stem/progenitor cells and was associated with downregulation of potentially carcinogenic pathways and a reduction in the proliferation potential of this cell subpopulation in vitro and in vivo. As a possible mechanism for decreased Wnt signaling in basal stem/progenitor cells, we found a more than threefold reduction in the expression of the secreted Wnt ligand Wnt4 in total mammary cells from parous mice, which corresponded to a similar decrease in the proportion of Wnt4-secreting and estrogen/progesterone receptor-positive cells. Because recombinant Wnt4 rescued the proliferation defect of basal stem/progenitor cells in vitro, reduced Wnt4 secretion appears to be causally related to parity-induced alterations of basal stem/progenitor cell properties in mice. Conclusions By revealing that parity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice, our study sheds light on the long-term consequences of an early pregnancy. Furthermore, it opens the door to future studies assessing whether inhibitors of the Wnt pathway may be used to mimic the parity-induced protective effect against breast cancer. PMID:23621987

Brain Cancer Stem Cells Display Preferential Sensitivity to Akt Inhibition

PubMed Central

Eyler, Christine E.; Foo, Wen-Chi; LaFiura, Katherine M.; McLendon, Roger E.; Hjelmeland, Anita B.; Rich, Jeremy N.

2009-01-01

Malignant brain tumors are among the most lethal cancers, and conventional therapies are largely limited to palliation. Novel therapies targeted against specific molecular pathways may offer improved efficacy and reduced toxicity compared to conventional therapies, but initial clinical trials of molecular targeted agents in brain cancer therapy have been frequently disappointing. In brain tumors and other cancers, subpopulations of tumor cells have recently been characterized by their ability to self-renew and initiate tumors. Although these cancer stem cells, or tumor initiating cells, are often only present in small numbers in human tumors, mounting evidence suggests that cancer stem cells contribute to tumor maintenance and therapeutic resistance. Thus, the development of therapies that target cancer stem cell signal transduction and biologies may improve brain tumor patient survival. We now demonstrate that populations enriched for cancer stem cells are preferentially sensitive to an inhibitor of Akt, a prominent cell survival and invasion signaling node. Treatment with an Akt inhibitor more potently reduced the numbers of viable brain cancer stem cells relative to matched non-stem cancer cells associated with a preferential induction of apoptosis and a suppression of neurosphere formation. Akt inhibition also reduced the motility and invasiveness of all tumor cells but had a greater impact on cancer stem cell behaviors. Furthermore, inhibition of Akt activity in cancer stem cells increased survival of immunocompromised mice bearing human glioma xenografts in vivo. Together, these results suggest that Akt inhibitors may function as effective anti-cancer stem cell therapies. PMID:18802038

Neural-network-based system for recognition of partially occluded shapes and patterns

NASA Astrophysics Data System (ADS)

Mital, Dinesh P.; Teoh, Eam-Khwang; Amarasinghe, S. K.; Suganthan, P. N.

1996-10-01

The purpose of this paper is to demonstrate how a structural matching approach can be used to perfonn effective rotational invariant fingerprint identification. In this approach, each of the exiracted features is correlated with Live of its nearest neighbouring features to form a local feature gmup for a first-stage matching. After that, the feature with the highest match is used as a central feature whereby all the other features are correlated to form a global feature group for a second.stage matching. The correlation between the features is in terms of distance and relative angle. This approach actually make the matching method rotational invariant A substantial amount of testing was carried out and it shows that this matching technique is capable of matching the four basic fingerprint patterns with an average matching time of4 seconds on a 66Mhz, 486 DX personal computer.

Identification of biomarkers associated with partial epithelial to mesenchymal transition in the secretome of slug over-expressing hepatocellular carcinoma cells.

PubMed

Karaosmanoğlu, Oğuzhan; Banerjee, Sreeparna; Sivas, Hülya

2018-06-01

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Complete epithelial to mesenchymal transition (EMT) has long been considered as a crucial step for metastasis initiation. It has, however, become apparent that many carcinoma cells can metastasize without complete loss of epithelial traits or with incomplete gain of mesenchymal traits, i.e., partial EMT. Here, we aimed to determine the similarities and differences between complete and partial EMT through over-expression of the EMT-associated transcription factor Slug in different HCC-derived cell lines. Slug over-expressing HCC-derived HepG2 and Huh7 cells were assessed for their EMT, chemo-resistance and stemness features using Western blotting, qRT-PCR, neutral red uptake, doxorubicin accumulation and scratch wound healing assays. We also collected conditioned media from Slug over-expressing HCC cells and analyzed its exosomal protein content for the presence of chemo-resistance and partial EMT markers using MALDI-TOF/TOF and ELISA assays, respectively. We found that Slug over-expression resulted in the induction of both complete and partial EMT in the different HCC-derived cell lines tested. Complete EMT was characterized by downregulation of E-cadherin and upregulation of ZEB2. Partial EMT was characterized by upregulation of E-cadherin and downregulation of vimentin and ZEB2. Interestingly, we found that Slug induced chemo-resistance through downregulation of the ATP binding cassette (ABC) transporter ABCB1 and upregulation of the ABC transporter ABCG2, as well as through expression of CD133, a stemness marker that exhibited a similar expression pattern in cells with either a complete or a partial EMT phenotype. In addition, we found that Slug-mediated partial EMT was associated with enhanced exosomal secretion of post-translationally modified fibronectin 1 (FN1), collagen type II alpha 1 (COL2A1) and native fibrinogen gamma chain (FGG). From our data we conclude that the exosomal proteins identified may be considered as potential non-invasive biomarkers for chemo-resistance and partial EMT in HCC.

Recognition and Matching of Clustered Mature Litchi Fruits Using Binocular Charge-Coupled Device (CCD) Color Cameras

PubMed Central

Wang, Chenglin; Tang, Yunchao; Zou, Xiangjun; Luo, Lufeng; Chen, Xiong

2017-01-01

Recognition and matching of litchi fruits are critical steps for litchi harvesting robots to successfully grasp litchi. However, due to the randomness of litchi growth, such as clustered growth with uncertain number of fruits and random occlusion by leaves, branches and other fruits, the recognition and matching of the fruit become a challenge. Therefore, this study firstly defined mature litchi fruit as three clustered categories. Then an approach for recognition and matching of clustered mature litchi fruit was developed based on litchi color images acquired by binocular charge-coupled device (CCD) color cameras. The approach mainly included three steps: (1) calibration of binocular color cameras and litchi image acquisition; (2) segmentation of litchi fruits using four kinds of supervised classifiers, and recognition of the pre-defined categories of clustered litchi fruit using a pixel threshold method; and (3) matching the recognized clustered fruit using a geometric center-based matching method. The experimental results showed that the proposed recognition method could be robust against the influences of varying illumination and occlusion conditions, and precisely recognize clustered litchi fruit. In the tested 432 clustered litchi fruits, the highest and lowest average recognition rates were 94.17% and 92.00% under sunny back-lighting and partial occlusion, and sunny front-lighting and non-occlusion conditions, respectively. From 50 pairs of tested images, the highest and lowest matching success rates were 97.37% and 91.96% under sunny back-lighting and non-occlusion, and sunny front-lighting and partial occlusion conditions, respectively. PMID:29112177

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

PubMed Central

Kumar, Rajat; Kimura, Fumihiko; Ahn, Kwang Woo; Hu, Zhen-Huan; Kuwatsuka, Yachiyo; Klein, John P.; Pasquini, Marcelo; Miyamura, Koichi; Kato, Koji; Yoshimi, Ayami; Inamoto, Yoshihiro; Ichinohe, Tatsuo; Wood, William Allen; Wirk, Baldeep; Seftel, Matthew; Rowlings, Philip; Marks, David I; Schultz, Kirk R.; Gupta, Vikas; Dedeken, Laurence; George, Biju; Cahn, Jean-Yves; Szer, Jeff; Lee, Jong Wook; Ho, Aloysius YL; Fasth, Anders; Hahn, Theresa; Khera, Nandita; Dalal, Jignesh; Bonfim, Carmem; Aljurf, Mahmoud; Atsuta, Yoshiko; Saber, Wael

2016-01-01

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared to mobilized peripheral blood stem cells (PBSC). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita (GNI) and region/countries into four groups. Groups analyzed were high income countries (HIC), which were further divided into US-Canada (N=486) and other HIC (N=1264), upper middle-income (UMIC) (N=482), and combined lower middle, low income countries (LM-LIC) (N=142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared to PBSC in all countries or BM in UMIC or LM-LIC (p<0.001). There was no significant difference in OS between BM and PBSC in UMIC (p=0.32) or LM-LIC (p=0.23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSC compared to BM (97% vs. 77%, p<0.001). Chronic GVHD was significantly higher with PBSC in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSC may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications. PMID:26797402

Amniotic-Fluid Stem Cells: Growth Dynamics and Differentiation Potential after a CD-117-Based Selection Procedure

PubMed Central

Arnhold, S.; Glüer, S.; Hartmann, K.; Raabe, O.; Addicks, K.; Wenisch, S.; Hoopmann, M.

2011-01-01

Amniotic fluid (AF) has become an interesting source of fetal stem cells. However, AF contains heterogeneous and multiple, partially differentiated cell types. After isolation from the amniotic fluid, cells were characterized regarding their morphology and growth dynamics. They were sorted by magnetic associated cell sorting using the surface marker CD 117. In order to show stem cell characteristics such as pluripotency and to evaluate a possible therapeutic application of these cells, AF fluid-derived stem cells were differentiated along the adipogenic, osteogenic, and chondrogenic as well as the neuronal lineage under hypoxic conditions. Our findings reveal that magnetic associated cell sorting (MACS) does not markedly influence growth characteristics as demonstrated by the generation doubling time. There was, however, an effect regarding an altered adipogenic, osteogenic, and chondrogenic differentiation capacity in the selected cell fraction. In contrast, in the unselected cell population neuronal differentiation is enhanced. PMID:21437196

Stem cell research and regenerative medicine in 2014: first year of regenerative medicine in Japan.

PubMed

Okano, Hideyuki

2014-09-15

It is my great pleasure to announce that we were able to publish the Japan Issue in Stem Cells and Development, especially in this year 2014. This year, 2014, is said to be the First Year of Regenerative Medicine in Japan. This movement is likely to be based on the establishment of a new law system regarding regenerative medicine (an Act for Ensuring the Safety of Regenerative Medicine or the so-called Regenerative Medicine Law) and the partial revision of the Pharmaceutical Affairs Law (PAL). Both laws will come into effect in 2014 in this country. These new law systems are expected to have a great impact on the facilitation of R&D related to regenerative medicine and stem cell biology. In the present Japan Issue, some excellent stem cell research in this country will be introduced to celebrate the First Year of Regenerative Medicine in Japan.

Transplantation of induced pluripotent stem cells improves functional recovery in Huntington's disease rat model.

PubMed

Mu, Shuhua; Wang, Jiachuan; Zhou, Guangqian; Peng, Wenda; He, Zhendan; Zhao, Zhenfu; Mo, CuiPing; Qu, Junle; Zhang, Jian

2014-01-01

The purpose of this study was to determine the functional recovery of the transplanted induced pluripotent stem cells in a rat model of Huntington's disease with use of 18F-FDG microPET/CT imaging. In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle ten days after the quinolinic acid injection. The response to the treatment was evaluated by serial 18F-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation. After induced pluripotent stem cells transplantation, higher 18F-FDG accumulation in the injured striatum was observed during the 4 to 6-weeks period compared with the quinolinic acid-injected group, suggesting the metabolic recovery of injured striatum. The induced pluripotent stem cells transplantation improved learning and memory function (and striatal atrophy) of the rat in six week in the comparison with the quinolinic acid-treated controls. In addition, immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated into the lesioned area in striatum, and most of the stem cells expressed protein markers of neurons and glial cells. Our findings show that induced pluripotent stem cells can survive, differentiate to functional neurons and improve partial striatal function and metabolism after implantation in a rat Huntington's disease model.

Stimulation with lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae maximizes cross-reactivity of anti-fungal T cells.

PubMed

Deo, Shivashni S; Virassamy, Balaji; Halliday, Catriona; Clancy, Leighton; Chen, Sharon; Meyer, Wieland; Sorrell, Tania C; Gottlieb, David J

2016-01-01

Invasive fungal diseases caused by filamentous fungi and yeasts are significant causes of morbidity and mortality in immunosuppressed hematology patients. We previously published a method to expand Aspergillus fumigatus-specific T cells for clinical cell therapy. In the present study, we investigated expansion of T cells specific for other fungal pathogens and creation of a broadly reactive panfungal T-cell product. Fungal strains selected were those frequently observed in the clinical hematology setting and included Aspergillus, Candida, Fusarium, Rhizopus and Lomentospora/Scedosporium. Four T-cell cultures specific to each fungus were established. We selected lysates of Aspergillus terreus, Candida krusei and Rhizopus oryzae to expand panfungal T cells. Allelic restriction of anti-fungal activity was determined through the use of specific major histocompatibility complex class II-blocking antibodies. Individual T-cell cultures specific to each fungus could be expanded in vitro, generating predominantly CD4(+) T cells of which 8% to 20% were fungus-specific. We successfully expanded panfungal T cells from the peripheral blood (n = 8) and granulocyte-colony-stimulating factor-primed stem cell products (n = 3) of normal donors by using a combination of lysates from Aspergillus terreus, Candida krusei and Rhizopus oryzae. Anti-fungal activity was mediated through human leukocyte antigen (HLA)-DR alleles and was maintained when antigen-presenting cells from partially HLA-DRB1-matched donors were used to stimulate T cells. We demonstrate a method to manufacture panfungal T-cell products with specificity against a range of clinical fungal pathogens by use of the blood and stem cells of healthy donors as the starting material. The safety and efficacy of these products will need to be tested clinically. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The Royan Public Umbilical Cord Blood Bank: Does It Cover All Ethnic Groups in Iran Based on HLA Diversity?

PubMed

Ebrahimkhani, Saeideh; Farjadian, Shirin; Ebrahimi, Marzieh

2014-04-01

Umbilical cord blood (UCB) stem cells allow the transplantation of partially human leukocyte antigen (HLA)-matched grafts and are a valuable resource for the treatment of hematologic malignancies and heritable hematologic, immunologic and metabolic diseases, especially when a compatible bone marrow donor is unavailable. The aim of this study was to determine how many ethnic groups in Iran are covered by the available UCB units based on HLA diversity. From 2009 until mid-2013, 4,981 (30.3%) of the 16,437 UCB samples collected met the storage criteria and were cryopreserved at a public cord blood bank (CBB) in Tehran, Iran. HLA-A, -B and -DRB1 were typed in 1,793 samples. The mean volume of the cryopreserved samples was 81.25 ± 20.3 ml. The range of total nucleated cells per unit was 51 × 10(7)-107 × 10(7). The most common HLA alleles were HLA-A*2 (17%) and HLA-A*24 (15.6%), HLA-B*35 (16.8%) and HLA-B*51 (13.9%), and HLA-DRB1*11 (20%) and HLA-DRB1*15 (14%). The predominant haplotypes were HLA-A*24-B*35-DRB1*11 (2%), HLA-A*02-B*50-DR*07 (1.8%), and HLA-A*02-B*51-DRB1*11 (1.5%). Based on the HLA-DRB1 profiles, the UCB units available at the Royan public UCB bank are a potentially adequate resource for hematopoietic stem cell transplantation for Iranian recipients belonging to particular ethnic groups. Regular educational programs to improve the public knowledge of UCB for transplantation can enhance the public CBB stocks for all Iranian ethnic groups in the future.

Autologous cord blood transfusion in preterm infants - could its humoral effect be the kez to control prematurity-related complications? A preliminary study.

PubMed

Kotowski, M; Litwinska, Z; Klos, P; Pius-Sadowska, E; Zagrodnik-Ulan, E; Ustianowski, P; Rudnicki, J; Machalinski, B

2017-12-01

Umbilical cord blood (UCB), rich in stem/progenitor cells, is partially eliminated from the bloodstream during childbirth because the cord is immediately clamped. We hypothesize that transfusion of autologous UCB to premature infants after delivery could serve as an adjuvant modality for preventing the development of prematurity-related complications. We randomly enrolled 20 preterm infants born before 32 weeks of gestational age (GA), all of whom developed anemia, necessitating transfusion of red blood cells (RBCs). Two groups, matched for GA, were selected: (1) infants (n = 5) who underwent UCB transfusion once within 5 days of birth (mean ± standard deviation, 3.2 ± 1.9 days) and (2) infants (n = 15) from whom UCB was not collected (e.g., lack of consent). The latter served as controls and received allogeneic RBC transfusions (7.8 ± 3.9 days after birth). Selected prematurity-related complications were monitored. Two weeks after UCB/RBC transfusion, peripheral blood samples were collected, and the concentrations of 41 selected growth factors and their receptors were analyzed using a multiplex protein array. UCB transfusions were found to be both feasible and tolerable. Intraventricular haemorrhage was diagnosed in two of five (40%) UCB recipients, but was found in thirteen of fifteen RBC recipients (86.7%). Twenty-two plasma proteins (e.g., insulin-like growth factors, stem cell factor, epidermal growth factors) were found with significantly different concentrations in UCB recipients compared to controls. Results demonstrate safety and feasibility of UCB transfusion in a small group of very premature neonates and should be interpreted as preliminary speculation. Transfusion of UCB could induce a specific humoral effects, and this could serve as an adjuvant modality for prevention of prematurity complications.

Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks

PubMed Central

Wang, Yingying; Chang, Jianhui; Shao, Lijian; Feng, Wei; Luo, Yi; Chow, Marie; Du, Wei; Meng, Aimin; Zhou, Daohong

2016-01-01

Down syndrome (DS) is a genetic disorder caused by the presence of an extra partial or whole copy of chromosome 21. In addition to musculoskeletal and neurodevelopmental abnormalities, children with DS exhibit various hematologic disorders and have an increased risk of developing acute lymphoblastic leukemia and acute megakaryocytic leukemia. Using the Ts65Dn mouse model, we investigated bone marrow defects caused by trisomy for 132 orthologs of the genes on human chromosome 21. The results showed that, although the total bone marrow cellularity as well as the frequency of hematopoietic progenitor cells (HPCs) was comparable between Ts65Dn mice and their age-matched euploid wild-type (WT) control littermates, human chromosome 21 trisomy led to a significant reduction in hematopoietic stem cell (HSC) numbers and clonogenic function in Ts65Dn mice. We also found that spontaneous DNA double-strand breaks (DSBs) were significantly increased in HSCs from the Ts65Dn mice, which was correlated with the significant reduction in HSC clonogenic activity compared to those from WT controls. Moreover, analysis of the repair kinetics of radiation-induced DSBs revealed that HSCs from Ts65Dn mice were less proficient in DSB repair than the cells from WT controls. This deficiency was associated with a higher sensitivity of Ts65Dn HSCs to radiation-induced suppression of HSC clonogenic activity than that of euploid HSCs. These findings suggest that an additional copy of genes on human chromosome 21 may selectively impair the ability of HSCs to repair DSBs, which may contribute to DS-associated hematological abnormalities and malignancies. PMID:27243896

Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy.

PubMed

Vicente-Dueñas, Carolina; Hauer, Julia; Ruiz-Roca, Lucía; Ingenhag, Deborah; Rodríguez-Meira, Alba; Auer, Franziska; Borkhardt, Arndt; Sánchez-García, Isidro

2015-06-01

Cancer is a clonal malignant disease originated in a single cell and characterized by the accumulation of partially differentiated cells that are phenotypically reminiscent of normal stages of differentiation. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumor cells. However, recent evidences have revealed that cancer stem cells could arise through a tumor stem cell reprogramming mechanism, suggesting that genetic lesions that initiate the cancer process might be dispensable for tumor progression and maintenance. This review addresses the impact of these results toward a better understanding of cancer development and proposes new approaches to treat cancer in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative Analysis of Mass Spectral Similarity Measures on Peak Alignment for Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry

PubMed Central

2013-01-01

Peak alignment is a critical procedure in mass spectrometry-based biomarker discovery in metabolomics. One of peak alignment approaches to comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) data is peak matching-based alignment. A key to the peak matching-based alignment is the calculation of mass spectral similarity scores. Various mass spectral similarity measures have been developed mainly for compound identification, but the effect of these spectral similarity measures on the performance of peak matching-based alignment still remains unknown. Therefore, we selected five mass spectral similarity measures, cosine correlation, Pearson's correlation, Spearman's correlation, partial correlation, and part correlation, and examined their effects on peak alignment using two sets of experimental GC×GC-MS data. The results show that the spectral similarity measure does not affect the alignment accuracy significantly in analysis of data from less complex samples, while the partial correlation performs much better than other spectral similarity measures when analyzing experimental data acquired from complex biological samples. PMID:24151524

Roadblocks en route to the clinical application of induced pluripotent stem cells.

PubMed

Lowry, William E; Quan, William L

2010-03-01

Since the first studies of human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs), the stem-cell field has been abuzz with the promise that these pluripotent populations will one day be a powerful therapeutic tool. Although it has been proposed that hiPSCs will supersede hESCs with respect to their research and/or clinical potential because of the ease of their derivation and the ability to create immunologically matched iPSCs for each individual patient, recent evidence suggests that iPSCs in fact have several underappreciated characteristics that might mean they are less suitable for clinical application. Continuing research is revealing the similarities, differences and deficiencies of various pluripotent stem-cell populations, and suggests that many years will pass before the clinical utility of hESCs and hiPSCs is realized. There are a plethora of ethical, logistical and technical roadblocks on the route to the clinical application of pluripotent stem cells, particularly of iPSCs. In this Essay, we discuss what we believe are important issues that should be considered when attempting to bring hiPSC-based technology to the clinic.

A critical review of which children with acute myeloid leukaemia need stem cell procedures.

PubMed

Hasle, Henrik

2014-07-01

The last decades have seen parallel improvements in chemotherapy-based and haematopoietic stem cell transplantation (HSCT) regimens for acute myeloid leukaemia (AML) in children. There has been no consensus on indication for HSCT. Reserving HSCT for high-risk and relapsed patients spare many patients from the long-term toxicity of this treatment. The results of matched unrelated donor HSCT equal family donor transplantation and the presence of a matched sibling should no longer be a transplant indication. Minimal residual disease measured by flow cytometry may identify poor responders benefitting from HSCT in first complete remission (CR1) and those with a favourable response to induction therapy who do not need HSCT even with adverse cytogenetic aberrations. FLT3-internal tandem duplication without NPM1 mutation has a very high relapse rate despite favourable response and HSCT is indicated in CR1 in these cases. Finding the optimal indications for HSCT is a delicate balance between risk of relapse and late effects. © 2014 John Wiley & Sons Ltd.

How I manage patients with Fanconi anaemia.

PubMed

Dufour, Carlo

2017-07-01

Fanconi Anaemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. Twenty genes have been reported to cause the disease. Remarkable progress has been made over the last 20 years in the understanding of the genetic and pathophysiological mechanisms. Unfortunately, these advances have not been completely paralleled by advances in medical treatment, where the most important component remains stem cell transplantation. This therapy, although contributing to long-term negative effects, such as increased occurrence of late malignancies, is the only current option capable of prolonging the survival of patients. In spite of relevant recent progress in matched unrelated donor transplants, the largest studies with longer follow-up still show a superiority of matched sibling donor transplants with a success rate, in selected cohorts, of over 90%. This article reviews different aspects of the disease, including genetics, diagnosis and treatment options, with special focus on stem cell transplantation, comprehensive post-diagnosis management, decision-making processes and long-term follow-up. © 2017 John Wiley & Sons Ltd.

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT.

PubMed

van Gorkom, Gwendolyn; van Gelder, Michel; Eikema, Dirk-Jan; Blok, Henric-Jan; van Lint, M T; Koc, Yener; Ciceri, Fabio; Beelen, Dietrich; Chevallier, Patrice; Selleslag, Dominik; Blaise, Didier; Foá, Roberto; Corradini, Paolo; Castagna, Luca; Moreno, Carol; Solano, Carlos; Müller, Lutz Peter; Tischer, Johanna; Hilgendorf, Inken; Hallek, Michael; Bittenbring, Jörg; Theobald, Matthias; Schetelig, Johannes; Kröger, Nicolaus

2018-03-01

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.

Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia.

PubMed

Zhu, Hua; Luo, Rong Mu; Luan, Zuo; Lee, Vincent; Zhu, Yi Ping; Luo, Cheng Juan; Tang, Xiang Feng; Si, Ying Jian; Chen, Jing

2016-09-01

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) used to be a third-line treatment option for childhood severe aplastic anaemia (SAA). We conducted this retrospective study of 36 children (38 transplants) who received haplo-HSCT from human leucocyte antigen (HLA)-mismatched related donors between July 2002 and November 2013 at five HSCT centres in China, including 17 cases that were 5/6 HLA matched (Group 1) and 21 that were 4/6 or 3/6 HLA matched (Group 2). Although patients in Group 2 had a higher incidence of grade II-IV acute graft-versus-host disease (57·9% vs. 5·9%, P = 0·001), they had similar rates of graft failure (5·3% vs. 5·9%, P = 0·742) and overall survival (80·8% vs. 93·8%, P = 0·234) as Group 1. Unmanipulated haplo-HSCT is an effective treatment for SAA children with satisfactory outcome of this cohort, especially in the 5/6 HLA-matched group. For patients in critical situations, such as unresponsive to immunosuppressive therapy, refractory infection and failing first HSCT, to bring forward the timing of haplo-HSCT is a feasible salvage strategy with better and faster donor accessibility. © 2016 John Wiley & Sons Ltd.

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

PubMed

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

Relationship between plant traits and resistance to burial by marly sediment

NASA Astrophysics Data System (ADS)

Burylo, M.; Rey, F.; Dutoit, T.

2009-04-01

In marly lands of the French Southern Alps, harsh soil erosion results in sediment movements during intensive rainfall events. Plants can be submitted to sediment burial in their early stages of development and their protective function may be reduced. In a context of land restoration, it is important to know species resistance to environmental disturbances and to be able to predict it, in particular from plant traits (height, biomass, sugar and starch accumulation). However, few studies about woody species tolerance to burial by sediment have been carried out. Seedlings of five woody species were buried in marly sediment at three different depths in pot experiment during eight weeks: no burial (control), partial burial (50% stem height) and complete burial (100% stem height). Height through time, biomass and survival rates were measured to assess species resistance to burial. Results show that among the five species, only one (Acer campestre) survived complete burial. All plants survived partial burial, but there were significant differences in height and biomass between buried plants and control, and significant differences between species responses. Three different responses to disturbance were identified: negative (Hippophae rhamnoides, Ononis fruticosa), neutral (Robinia pseudo acacia, Pinus nigra) and positive (Acer campestre). Results finally suggest that species resistance to burial by marly sediment is related to sugar accumulation in plant stems.

Monitoring the effect of mechanical stress on mesenchymal stem cell collagen production by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Chen, Wei-Liang; Chang, Chia-Cheng; Chiou, Ling-Ling; Li, Tsung-Hsien; Liu, Yuan; Lee, Hsuan-Shu; Dong, Chen-Yuan

2008-02-01

Tissue engineering is emerging as a promising method for repairing damaged tissues. Due to cartilage's common wear and injury, in vitro production of cartilage replacements have been an active area of research. Finding the optimal condition for the generation of the collagen matrix is crucial in reproducing cartilages that closely match those found in human. Using multiphoton autofluorescence and second-harmonic generation (SHG) microscopy we monitored the effect of mechanical stress on mesenchymal stem cell collagen production. Bone marrow mesenchymal stem cells in the form of pellets were cultured and periodically placed under different mechanical stress by centrifugation over a period of four weeks. The differently stressed samples were imaged several times during the four week period, and the collagen production under different mechanical stress is characterized.

A perspective on the selection of unrelated donors and cord blood units for transplantation

PubMed Central

Spellman, Stephen R.; Eapen, Mary; Logan, Brent R.; Mueller, Carlheinz; Rubinstein, Pablo; Setterholm, Michelle I.; Woolfrey, Ann E.; Confer, Dennis L.; Hurley, Carolyn K.

2012-01-01

Selection of a suitable graft for allogeneic hematopoietic stem cell transplantation involves consideration of both donor and recipient characteristics. Of primary importance is sufficient donor-recipient HLA matching to ensure engraftment and acceptable rates of GVHD. In this Perspective, the National Marrow Donor Program and the Center for International Blood and Marrow Transplant Research provide guidelines, based on large studies correlating graft characteristics with clinical transplantation outcomes, on appropriate typing strategies and matching criteria for unrelated adult donor and cord blood graft selection. PMID:22596257

Transcriptional programming during cell wall maturation in the expanding Arabidopsis stem.

PubMed

Hall, Hardy; Ellis, Brian

2013-01-25

Plant cell walls are complex dynamic structures that play a vital role in coordinating the directional growth of plant tissues. The rapid elongation of the inflorescence stem in the model plant Arabidopsis thaliana is accompanied by radical changes in cell wall structure and chemistry, but analysis of the underlying mechanisms and identification of the genes that are involved has been hampered by difficulties in accurately sampling discrete developmental states along the developing stem. By creating stem growth kinematic profiles for individual expanding Arabidopsis stems we have been able to harvest and pool developmentally-matched tissue samples, and to use these for comparative analysis of global transcript profiles at four distinct phases of stem growth: the period of elongation rate increase, the point of maximum growth rate, the point of stem growth cessation and the fully matured stem. The resulting profiles identify numerous genes whose expression is affected as the stem tissues pass through these defined growth transitions, including both novel loci and genes identified in earlier studies. Of particular note is the preponderance of highly active genes associated with secondary cell wall deposition in the region of stem growth cessation, and of genes associated with defence and stress responses in the fully mature stem. The use of growth kinematic profiling to create tissue samples that are accurately positioned along the expansion growth continuum of Arabidopsis inflorescence stems establishes a new standard for transcript profiling analyses of such tissues. The resulting expression profiles identify a substantial number of genes whose expression is correlated for the first time with rapid cell wall extension and subsequent fortification, and thus provide an important new resource for plant biologists interested in gene discovery related to plant biomass accumulation.

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

PubMed Central

Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

DUK - A Fast and Efficient Kmer Based Sequence Matching Tool

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

Li, Mingkun; Copeland, Alex; Han, James

2011-03-21

A new tool, DUK, is developed to perform matching task. Matching is to find whether a query sequence partially or totally matches given reference sequences or not. Matching is similar to alignment. Indeed many traditional analysis tasks like contaminant removal use alignment tools. But for matching, there is no need to know which bases of a query sequence matches which position of a reference sequence, it only need know whether there exists a match or not. This subtle difference can make matching task much faster than alignment. DUK is accurate, versatile, fast, and has efficient memory usage. It uses Kmermore » hashing method to index reference sequences and Poisson model to calculate p-value. DUK is carefully implemented in C++ in object oriented design. The resulted classes can also be used to develop other tools quickly. DUK have been widely used in JGI for a wide range of applications such as contaminant removal, organelle genome separation, and assembly refinement. Many real applications and simulated dataset demonstrate its power.« less

Post-traumatic unilateral plantar hyperhidrosis.

PubMed

Eren, Y; Yavasoglu, N G; Comoglu, S S

2016-02-01

Localized unilateral hyperhidrosis is rare and poorly understood, sometimes stemming from trauma. Feet, quite vulnerable to trauma are affected by disease-mediated plantar hyperhidrosis, usually bilaterally. This report describes partial hyperhidrosis developing post-traumatically on the left plantar region of a 52-year-old male.

Genomic analysis of soybean defense response to Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

We have conducted microarray studies on changes in soybean transcript levels in response to Sclerotinia sclerotiorum infection. These stem inoculations enabled us to identify genes that are differentially expressed in soybean plants in partially resistant versus susceptible varieties. We are expandi...

Selectively active markers for solving of the partial occlusion problem in matchmoving and chromakeying workflow

NASA Astrophysics Data System (ADS)

Mazurek, Przemysław

2013-09-01

Matchmoving (Match Moving) is the process used for the estimation of camera movements for further integration of acquired video image with computer graphics. The estimation of movements is possible using pattern recognition, 2D and 3D tracking algorithms. The main problem for the workflow is the partial occlusion of markers by the actor, because manual rotoscoping is necessary for fixing of the chroma-keyed footage. In the paper, the partial occlusion problem is solved using the invented, selectively active electronic markers. The sensor network with multiple infrared links detects occlusion state (no-occlusion, partial, full) and switch LED's based markers.

Index of stations: surface-water data-collection network of Texas, September 1999

USGS Publications Warehouse

Gandara, Susan C.; Barbie, Dana L.

2001-01-01

As of September 30, 1999, the surface-water data-collection network of Texas (table 1) included 321 continuous-record streamflow stations (D), 20 continuous-record gage-height only stations (G), 24 crest-stage partial-record stations (C), 40 floodhydrograph partial-record stations (H), 25 low-flow partial-record stations (L), 1 continuous-record temperature station (M1), 25 continuous-record temperature and specific conductance stations (M2), 17 continuous-record temperature, specific conductance, dissolved oxygen, and pH stations (M4), 4 daily water-quality stations (Qd), 115 periodic water-quality stations (Qp), 17 reservoir/lake surveys for water quality stations (Qs), 85 continuous or daily reservoircontent stations (R), and 10 daily precipitation stations (Pd). Plate 1 identifies the major river basins in Texas and shows the location of the stations listed in table 1. Table 1 shows the station number and name, latitude and longitude, type of station, and office responsible for the collection of the data and maintenance of the record. An 8-digit permanent numerical designation for all gaging stations has been adopted on a nationwide basis; stations are numbered and listed in downstream order. In the downstream direction along the main stem, all stations on a tributary entering between two main-stem stations are listed between these two stations. A similar order is followed in listing stations by first rank, second rank, and other ranks of tributaries. The rank of any tributary, with respect to the stream to which it is an immediate tributary, is indicated by an indention in the table. Each indention represents one rank. This downstream order and system of indention shows which gaging stations are on tributaries between any two stations on a main stem and the rank of the tributary on which each gaging station is situated.

Bmi1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor

PubMed Central

Biehs, Brian; Hu, Jimmy Kuang-Hsien; Strauli, Nicolas B.; Sangiorgi, Eugenio; Jung, Heekyung; Heber, Ralf-Peter; Ho, Sunita; Goodwin, Alice F.; Dasen, Jeremy S.; Capecchi, Mario R.; Klein, Ophir D.

2013-01-01

The polycomb group gene Bmi1 is required for maintenance of adult stem cells in many organs1, 2. Inactivation of Bmi1 leads to impaired stem cell self-renewal due to deregulated gene expression. One critical target of BMI1 is Ink4a/Arf, which encodes the cell cycle inhibitors p16ink4a and p19Arf3. However, deletion of Ink4a/Arf only partially rescues Bmi1 null phenotypes4, indicating that other important targets of BMI1 exist. Here, using the continuously-growing mouse incisor as a model system, we report that Bmi1 is expressed by incisor stem cells and that deletion of Bmi1 resulted in fewer stem cells, perturbed gene expression, and defective enamel production. Transcriptional profiling revealed that Hox expression is normally repressed by BMI1 in the adult, and functional assays demonstrated that BMI1-mediated repression of Hox genes preserves the undifferentiated state of stem cells. As Hox gene upregulation has also been reported in other systems when Bmi1 is inactivated1, 2, 5–7, our findings point to a general mechanism whereby BMI1-mediated repression of Hox genes is required for the maintenance of adult stem cells and for prevention of inappropriate differentiation. PMID:23728424

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

ARABIDOPSIS THALIANA HOMEOBOX GENE1 establishes the basal boundaries of shoot organs and controls stem growth.

PubMed

Gómez-Mena, Concepción; Sablowski, Robert

2008-08-01

Apical meristems play a central role in plant development. Self-renewing cells in the central region of the shoot meristem replenish the cell population in the peripheral region, where organ primordia emerge in a predictable pattern, and in the underlying rib meristem, where new stem tissue is formed. While much is known about how organ primordia are initiated and their lateral boundaries established, development at the interface between the stem and the meristem or the lateral organs is poorly understood. Here, we show that the BELL-type ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1) is required for proper development of the boundary between the stem and both vegetative and reproductive organs and that this role partially overlaps with that of CUP-SHAPED COTYLEDON genes. During the vegetative phase, ATH1 also functions redundantly with light-activated genes to inhibit growth of the region below the shoot meristem. Consistent with a role in inhibiting stem growth, ATH1 is downregulated at the start of inflorescence development and ectopic ATH1 expression prevents growth of the inflorescence stem by reducing cell proliferation. Thus, ATH1 modulates growth at the interface between the stem, meristem, and organ primordia and contributes to the compressed vegetative habit of Arabidopsis thaliana.

The differential effect of anticipated work-family conflict on the STEM major embeddedness of men and women

NASA Astrophysics Data System (ADS)

Myers, Dante P.

It is nationally concerning that many students who begin as Science, Technology, Engineering and Mathematics (STEM) majors do not complete their degrees. Of additional concern is that among the STEM students who do persist to degree completion, women are severely underrepresented. The present research investigates the extent to which anticipated conflicts between work and family life (AWFC) are negatively related to students' embeddedness in their STEM majors, especially the STEM embeddedness of women. The hypothesized model was tested using structural equation modeling in Mplus-7 with a sample of 218 STEM students from an archival database. As hypothesized, work-family decision making self-efficacy had a negative relationship with both anticipated work interference with family (AWIF) and anticipated family interference with work (AFIW). Notably, only AFIW was negatively related to major embeddedness and only the indirect effect of WFSE on major embeddedness through AFIW was positive and significant, partially supporting each corresponding hypothesis. Additionally, the relationships among study variables did not significantly differ by gender. However, the relationship between AFIW and major embeddedness approached significance for women. Implications of this research, future directions, and study limitations are discussed.

Conditioned medium as a strategy for human stem cells chondrogenic differentiation.

PubMed

Alves da Silva, M L; Costa-Pinto, A R; Martins, A; Correlo, V M; Sol, P; Bhattacharya, M; Faria, S; Reis, R L; Neves, Nuno M

2015-06-01

Paracrine signalling from chondrocytes has been reported to increase the synthesis and expression of cartilage extracellular matrix (ECM) by stem cells. The use of conditioned medium obtained from chondrocytes for stimulating stem cells chondrogenic differentiation may be a very interesting alternative for moving into the clinical application of these cells, as chondrocytes could be partially replaced by stem cells for this type of application. In the present study we aimed to achieve chondrogenic differentiation of two different sources of stem cells using conditioned medium, without adding growth factors. We tested both human bone marrow-derived mesenchymal stem cells (hBSMCs) and human Wharton's jelly-derived stem cells (hWJSCs). Conditioned medium obtained from a culture of human articular chondrocytes was used to feed the cells during the experiment. Cultures were performed in previously produced three-dimensional (3D) scaffolds, composed of a blend of 50:50 chitosan:poly(butylene succinate). Both types of stem cells were able to undergo chondrogenic differentiation without the addition of growth factors. Cultures using hWJSCs showed significantly higher GAGs accumulation and expression of cartilage-related genes (aggrecan, Sox9 and collagen type II) when compared to hBMSCs cultures. Conditioned medium obtained from articular chondrocytes induced the chondrogenic differentiation of MSCs and ECM formation. Obtained results showed that this new strategy is very interesting and should be further explored for clinical applications. Copyright © 2013 John Wiley & Sons, Ltd.

The bachelor’s to Ph.D. STEM pipeline no longer leaks more women than men: a 30-year analysis

PubMed Central

Miller, David I.; Wai, Jonathan

2015-01-01

For decades, research and public discourse about gender and science have often assumed that women are more likely than men to “leak” from the science pipeline at multiple points after entering college. We used retrospective longitudinal methods to investigate how accurately this “leaky pipeline” metaphor has described the bachelor’s to Ph.D. transition in science, technology, engineering, and mathematics (STEM) fields in the U.S. since the 1970s. Among STEM bachelor’s degree earners in the 1970s and 1980s, women were less likely than men to later earn a STEM Ph.D. However, this gender difference closed in the 1990s. Qualitatively similar trends were found across STEM disciplines. The leaky pipeline metaphor therefore partially explains historical gender differences in the U.S., but no longer describes current gender differences in the bachelor’s to Ph.D. transition in STEM. The results help constrain theories about women’s underrepresentation in STEM. Overall, these results point to the need to understand gender differences at the bachelor’s level and below to understand women’s representation in STEM at the Ph.D. level and above. Consistent with trends at the bachelor’s level, women’s representation at the Ph.D. level has been recently declining for the first time in over 40 years. PMID:25741293

Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

PubMed Central

Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

2015-01-01

Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

Using ClinicalTrials.gov to Supplement Information in Ophthalmology Conference Abstracts about Trial Outcomes: A Comparison Study

PubMed Central

Scherer, Roberta W.; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Background Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. Methods We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. Results We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching “new” outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conclusion Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned. PMID:26107924

Hydrous partial melting in the sheeted dike complex at fast spreading ridges: experimental and natural observations

NASA Astrophysics Data System (ADS)

France, Lydéric; Koepke, Juergen; Ildefonse, Benoit; Cichy, Sarah B.; Deschamps, Fabien

2010-11-01

In ophiolites and in present-day oceanic crust formed at fast spreading ridges, oceanic plagiogranites are commonly observed at, or close to the base of the sheeted dike complex. They can be produced either by differentiation of mafic melts, or by hydrous partial melting of the hydrothermally altered sheeted dikes. In addition, the hydrothermally altered base of the sheeted dike complex, which is often infiltrated by plagiogranitic veins, is usually recrystallized into granoblastic dikes that are commonly interpreted as a result of prograde granulitic metamorphism. To test the anatectic origin of oceanic plagiogranites, we performed melting experiments on a natural hydrothermally altered dike, under conditions that match those prevailing at the base of the sheeted dike complex. All generated melts are water saturated, transitional between tholeiitic and calc-alkaline, and match the compositions of oceanic plagiogranites observed close to the base of the sheeted dike complex. Newly crystallized clinopyroxene and plagioclase have compositions that are characteristic of the same minerals in granoblastic dikes. Published silicic melt compositions obtained in classical MORB fractionation experiments also broadly match the compositions of oceanic plagiogranites; however, the compositions of the coexisting experimental minerals significantly deviate from those of the granoblastic dikes. Our results demonstrate that hydrous partial melting is a likely common process in the root zone of the sheeted dike complex, starting at temperatures exceeding 850°C. The newly formed melt can either crystallize to form oceanic plagiogranites or may be recycled within the melt lens resulting in hybridized and contaminated MORB melts. It represents the main MORB crustal contamination process. The residue after the partial melting event is represented by the granoblastic dikes. Our results support a model with a dynamic melt lens that has the potential to trigger hydrous partial melting reactions in the previously hydrothermally altered sheeted dikes. A new thermometer using the Al content of clinopyroxene is also elaborated.

Quality of life after surgery for intractable partial epilepsy in children: a cohort study with controls.

PubMed

Mikati, Mohamad A; Ataya, Nour; Ferzli, Jessica; Kurdi, Rana; El-Banna, Diana; Rahi, Amal; Shamseddine, Alhan; Sinno, Durriyah; Comair, Youssef

2010-08-01

Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

Solving vertical and horizontal well hydraulics problems analytically in Cartesian coordinates with vertical and horizontal anisotropies

NASA Astrophysics Data System (ADS)

Batu, Vedat

2012-01-01

SummaryA new generalized three-dimensional analytical solution is developed for a partially-penetrating vertical rectangular parallelepiped well screen in a confined aquifer by solving the three-dimensional transient ground water flow differential equation in x- y- z Cartesian coordinates system for drawdown by taking into account the three principal hydraulic conductivities ( Kx, Ky, and Kz) along the x- y- z coordinate directions. The fully penetrating screen case becomes equivalent to the single vertical fracture case of Gringarten and Ramey (1973). It is shown that the new solution and Gringarten and Ramey solution (1973) match very well. Similarly, it is shown that this new solution for a horizontally tiny fully penetrating parallelepiped rectangular parallelepiped screen case match very well with Theis (1935) solution. Moreover, it is also shown that the horizontally tiny partially-penetrating parallelepiped rectangular well screen case of this new solution match very well with Hantush (1964) solution. This new analytical solution can also cover a partially-penetrating horizontal well by representing its screen interval with vertically tiny rectangular parallelepiped. Also the solution takes into account both the vertical anisotropy ( azx = Kz/ Kx) as well as the horizontal anisotropy ( ayx = Ky/ Kx) and has potential application areas to analyze pumping test drawdown data from partially-penetrating vertical and horizontal wells by representing them as tiny rectangular parallelepiped as well as line sources. The solution has also potential application areas for a partially-penetrating parallelepiped rectangular vertical fracture. With this new solution, the horizontal anisotropy ( ayx = Ky/ Kx) in addition to the vertical anisotropy ( azx = Kz/ Kx) can also be determined using observed drawdown data. Most importantly, with this solution, to the knowledge of the author, it has been shown the first time in the literature that some well-known well hydraulics problems can also be solved in Cartesian coordinates with some additional advantages other than the conventional cylindrical coordinates method.

Gravitropism in Higher Plant Shoots 1

PubMed Central

Wheeler, Raymond M.; White, Rosemary G.; Salisbury, Frank B.

1986-01-01

Ethylene at 1.0 and 10.0 cubic centimeters per cubic meter decreased the rate of gravitropic bending in stems of cocklebur (Xanthium strumarium L.) and tomato (Lycopersicon esculentum Mill), but 0.1 cubic centimeter per cubic meter ethylene had little effect. Treating cocklebur plants with 1.0 millimolar aminoethoxyvinylglycine (AVG) (ethylene synthesis inhibitor) delayed stem bending compared with controls, but adding 0.1 cubic centimeter per cubic meter ethylene in the surrounding atmosphere (or applying 0.1% ethephon solution) partially restored the rate of bending of AVG-treated plants. Ethylene increases in bending stems, and AVG inhibits this. Virtually all newly synthesized ethylene appeared in bottom halves of horizontal stems, where ethylene concentrations were as much as 100 times those in upright stems or in top halves of horizontal stems. This was especially true when horizontal stems were physically restrained from bending. Ethylene might promote cell elongation in bottom tissues of a horizontal stem or indicate other factors there (e.g. a large amount of `functioning' auxin). Or top and bottom tissues may become differentially sensitive to ethylene. Auxin applied to one side of a vertical stem caused extreme bending away from that side; gibberellic acid, kinetin, and abscisic acid were without effect. Acidic ethephon solutions applied to one side of young seedlings of cocklebur, tomato, sunflower (Helianthus annuus L.), and soybean (Glycine max [L.] Merr.) caused bending away from that side, but neutral ethephon solutions did not cause bending. Buffered or unbuffered acid (HCl) caused similar bending. Neutral ethephon solutions produced typical ethylene symptoms (i.e. epinasty, inhibition of stem elongation). HCl or acidic ethephon applied to the top of horizontal stems caused downward bending, but these substances applied to the bottom of such stems inhibited growth and upward bending—an unexpected result. PMID:11539089

Satellite Cell Self-Renewal.

PubMed

Giordani, Lorenzo; Parisi, Alice; Le Grand, Fabien

2018-01-01

Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological conditions, quiescent muscle-resident stem cells, called satellite cells, become activated and give rise to myogenic progenitors that massively proliferate, differentiate, and fuse to form new myofibers and restore tissue functionality. In addition, a proportion of activated cells returns back to quiescence and replenish the pool of satellite cells in order to maintain the ability of skeletal muscle tissue to repair. Self-renewal is the process by which stem cells divide to make more stem cells to maintain the stem cell population throughout life. This process is controlled by cell-intrinsic transcription factors regulated by cell-extrinsic signals from the niche and the microenvironment. This chapter provides an overview about the general aspects of satellite cell biology and focuses on the cellular and molecular aspects of satellite cell self-renewal. To date, we are still far from understanding how a very small proportion of the satellite cell progeny maintain their stem cell identity when most of their siblings progress through the myogenic program to construct myofibers. © 2018 Elsevier Inc. All rights reserved.

Virus-Specific T Cells for the Immunocompromised Patient

PubMed Central

Houghtelin, Amy; Bollard, Catherine M.

2017-01-01

While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70–90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo. PMID:29075259

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

PubMed

Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

2017-11-14

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

Virus-Specific T Cells for the Immunocompromised Patient.

PubMed

Houghtelin, Amy; Bollard, Catherine M

2017-01-01

While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70-90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo .

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells

PubMed Central

Withers, Barbara; Clancy, Leighton E.; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J.; Micklethwaite, Kenneth P.

2017-01-01

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo–expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718. PMID:29296867

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling

PubMed Central

Ho, Chia Chi M.; Chhabra, Akanksha; Starkl, Philipp; Schnorr, Peter-John; Wilmes, Stephan; Moraga, Ignacio; Kwon, Hye-Sook; Gaudenzio, Nicolas; Sibilano, Riccardo; Wehrman, Tom S.; Gakovic, Milica; Sockolosky, Jonathan T.; Tiffany, Matthew R.; Ring, Aaron M.; Piehler, Jacob; Weissman, Irving L.; Galli, Stephen J.; Shizuru, Judith A.; Garcia, K. Christopher

2017-01-01

SUMMARY Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion, but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems. PMID:28283060

The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy.

PubMed

Khoury, Maroun; Alcayaga-Miranda, Francisca; Illanes, Sebastián E; Figueroa, Fernando E

2014-01-01

Menstrual-derived stem cells (MenSCs) are a new source of mesenchymal stem cells isolated from the menstrual fluid. Currently, there is a growing interest in their clinical potential due to fact that they are multipotent, highly proliferative, and easy to obtain in a non-invasive manner. Sampling can be repeated periodically in a simplified and reproducible manner devoid of complications that no existing cell source can match. MenSCs are also free of ethical dilemmas, and display novel properties with regard to presently known adult derived stem cells. This review details their distinctive biological properties regarding immunophenotype and function, proliferation rate, differentiation potential, and paracrine effects mediated by secreted factors. Their possible role in antenatal diagnosis is also discussed. While more insight on their immunomodulatory and diagnostic properties is needed, the impact of clinical and epidemiological factors, such as age, use of contraceptives, or hormonal status still requires further investigations to properly assess their current and future use in clinical application and diagnosis.

A database linking Chinese patents to China’s census firms

PubMed Central

He, Zi-Lin; Tong, Tony W.; Zhang, Yuchen; He, Wenlong

2018-01-01

To meet researchers’ increasing interest in the fast growing innovation activities taking place in China, we match patents filed with China’s State Intellectual Property Office to firms covered in China’s Census. China has experienced a strong growth in patent filings over the past two decades, and has since 2011 become the world’s top patent filing country. China’s Census database covers about one million unique manufacturing firms from 1998–2009, representing the broad Chinese economy. We design data parsing and pre-processing routines to clean and stem firm and assignee names, create a matching algorithm that fits with our data and maintains a balance between matching accuracy and workload of manual check, and implement a systematic manual check process to filter out false positives generated from computerized matching. Our project generates 1,113,588 matches for the Census firms, among which 849,647 patents are uniquely matched. By creating the patent-firm linked dataset, we hope to reduce duplicative effort and encourage more research to better understand China’s fast changing innovation landscape. PMID:29583142

Predicting College Readiness in STEM: A Longitudinal Study of Iowa Students

NASA Astrophysics Data System (ADS)

Rickels, Heather Anne

The demand for STEM college graduates is increasing. However, recent studies show there are not enough STEM majors to fulfill this need. This deficiency can be partially attributed to a gender discrepancy in the number of female STEM graduates and to the high rate of attrition of STEM majors. As STEM attrition has been associated with students being unprepared for STEM coursework, it is important to understand how STEM graduates change in achievement levels from middle school through high school and to have accurate readiness indicators for first-year STEM coursework. This study aimed to address these issues by comparing the achievement growth of STEM majors to non-STEM majors by gender in Science, Math, and Reading from Grade 6 to Grade 11 through latent growth models (LGMs). Then STEM Readiness Benchmarks were established in Science and Math on the Iowas (IAs) for typical first-year STEM courses and validity evidence was provided for the benchmarks. Results from the LGM analyses indicated that STEM graduates start at higher achievement levels in Grade 6 and maintain higher achievement levels through Grade 11 in all subjects. In addition, gender differences were examined. The findings indicate that students with high achievement levels self-select as STEM majors, regardless of gender. In addition, they suggest that students who are not on-track for a STEM degree may need to begin remediation prior to high school. Results from the benchmark analyses indicate that STEM coursework is more demanding and that students need to be better prepared academically in science and math if planning to pursue a STEM degree. In addition, the STEM Readiness Benchmarks were more accurate in predicting success in STEM courses than if general college readiness benchmarks were utilized. Also, students who met the STEM Readiness Benchmarks were more likely to graduate with a STEM degree. This study provides valuable information on STEM readiness to students, educators, and college admissions officers. Findings from this study can be used to better understand the level of academic achievement necessary to be successful as a STEM major and to provide guidance for students considering STEM majors in college. If students are being encouraged to purse STEM majors, it is important they have accurate information regarding their chances of success in STEM coursework.

Geographic Trends in the Plastic Surgery Match.

PubMed

Silvestre, Jason; Lin, Ines C; Serletti, Joseph M; Chang, Benjamin

2016-01-01

The integrated plastic surgery match is among the most competitive residency matches in recent years. Although previous studies have correlated applicant characteristics with successful match outcomes, none have comprehensively investigated the role of geography in the match. This study elucidates regional biases in the match. Plastic surgery residents who matched during 2011-2015 were eligible for study inclusion. Names of residents were obtained from official residency program websites and cross-referenced with data obtained from the Student Doctor Network. For each resident, region of residency program and medical school were compared. From 67 programs, 622 residents were identified. Most graduated from US medical schools (97.9%). A total of 94 residents matched at a home institution (15.1%). Half of the residents matched in the same region as their medical school (48.9%). Programs in the South matched the greatest number of residents from the same region (60.8%), whereas West programs matched the least (30.8%, p < 0.001). No regional differences existed regarding residents matching at their home institution (p = 0.268). More women matched at West programs (43.1%) versus East programs (30.6%, p < 0.05). A significant number of residents matched at their home institution. Roughly, half matched at a program in the same region as their medical school. Whether this regional phenomenon stems from applicant or program factors remains unknown. Yet, given the limited number of interviews and the high costs of interviewing, applicants and programs can use these data to help optimize the match process. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation.

PubMed

Crocchiolo, Roberto; Zino, Elisabetta; Vago, Luca; Oneto, Rosi; Bruno, Barbara; Pollichieni, Simona; Sacchi, Nicoletta; Sormani, Maria Pia; Marcon, Jessica; Lamparelli, Teresa; Fanin, Renato; Garbarino, Lucia; Miotti, Valeria; Bandini, Giuseppe; Bosi, Alberto; Ciceri, Fabio; Bacigalupo, Andrea; Fleischhauer, Katharina

2009-08-13

The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for oncohematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher Kaplan-Meier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors.

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics

PubMed Central

La Nasa, Giorgio; Vacca, Adriana; Littera, Roberto; Piras, Eugenia; Orru, Sandro; Greco, Marianna; Carcassi, Carlo; Caocci, Giovanni

2016-01-01

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to significant rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individualize appropriate strategies for its prevention and management. This review provides an overview of recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia. PMID:27872728

Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation

PubMed Central

Ciurea, Stefan O.; Thall, Peter F.; Wang, Xuemei; Wang, Sa A.; Hu, Ying; Cano, Pedro; Aung, Fleur; Rondon, Gabriela; Molldrem, Jeffrey J.; Korbling, Martin; Shpall, Elizabeth J.; de Lima, Marcos; Champlin, Richard E.

2011-01-01

Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay. DSA identification was performed using single-Ag beads containing the corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116 patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%) patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P = .0014). In multivariate analysis, DSAs were the only factor highly associated with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation. PMID:21967975

Use of DNA profiles for investigation using a simulated national DNA database: Part II. Statistical and ethical considerations on familial searching.

PubMed

Hicks, T; Taroni, F; Curran, J; Buckleton, J; Castella, V; Ribaux, O

2010-10-01

Familial searching consists of searching for a full profile left at a crime scene in a National DNA Database (NDNAD). In this paper we are interested in the circumstance where no full match is returned, but a partial match is found between a database member's profile and the crime stain. Because close relatives share more of their DNA than unrelated persons, this partial match may indicate that the crime stain was left by a close relative of the person with whom the partial match was found. This approach has successfully solved important crimes in the UK and the USA. In a previous paper, a model, which takes into account substructure and siblings, was used to simulate a NDNAD. In this paper, we have used this model to test the usefulness of familial searching and offer guidelines for pre-assessment of the cases based on the likelihood ratio. Siblings of "persons" present in the simulated Swiss NDNAD were created. These profiles (N=10,000) were used as traces and were then compared to the whole database (N=100,000). The statistical results obtained show that the technique has great potential confirming the findings of previous studies. However, effectiveness of the technique is only one part of the story. Familial searching has juridical and ethical aspects that should not be ignored. In Switzerland for example, there are no specific guidelines to the legality or otherwise of familial searching. This article both presents statistical results, and addresses criminological and civil liberties aspects to take into account risks and benefits of familial searching. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

A digital matched filter for reverse time chaos.

PubMed

Bailey, J Phillip; Beal, Aubrey N; Dean, Robert N; Hamilton, Michael C

2016-07-01

The use of reverse time chaos allows the realization of hardware chaotic systems that can operate at speeds equivalent to existing state of the art while requiring significantly less complex circuitry. Matched filter decoding is possible for the reverse time system since it exhibits a closed form solution formed partially by a linear basis pulse. Coefficients have been calculated and are used to realize the matched filter digitally as a finite impulse response filter. Numerical simulations confirm that this correctly implements a matched filter that can be used for detection of the chaotic signal. In addition, the direct form of the filter has been implemented in hardware description language and demonstrates performance in agreement with numerical results.

A digital matched filter for reverse time chaos

NASA Astrophysics Data System (ADS)

Bailey, J. Phillip; Beal, Aubrey N.; Dean, Robert N.; Hamilton, Michael C.

2016-07-01

The use of reverse time chaos allows the realization of hardware chaotic systems that can operate at speeds equivalent to existing state of the art while requiring significantly less complex circuitry. Matched filter decoding is possible for the reverse time system since it exhibits a closed form solution formed partially by a linear basis pulse. Coefficients have been calculated and are used to realize the matched filter digitally as a finite impulse response filter. Numerical simulations confirm that this correctly implements a matched filter that can be used for detection of the chaotic signal. In addition, the direct form of the filter has been implemented in hardware description language and demonstrates performance in agreement with numerical results.

Five-year trends of second-hand smoke exposure in Greece: a comparison between complete, partial, and prelegislation levels.

PubMed

Vardavas, Constantine I; Anagnostopoulos, Nektarios; Patelarou, Evridiki; Minas, Markos; Nakou, Chrysanthi; Dramba, Vassiliki; Giourgouli, Gianna; Bagkeris, Emmanouil; Gourgoulianis, Konstantinos; Pattaka, Paraskevi; Antoniadis, Antonis; Lionis, Christos; Bertic, Monique; Dockery, Douglas; Connolly, Gregory N; Behrakis, Panagiotis K

2012-12-01

Our aim was to assess second-hand smoke (SHS) exposure in hospitality venues after the smoke-free legislation implemented in September 2010 in Greece and to compare with when a partial ban was in place and in 2006 when no ban was in place. Hospitality venues were prospectively assessed for their indoor concentrations of particulate matter (PM(2.5)) during the partial ban phase (n=149) and the complete ban phase (n=120, 80% followed up), while overall and matched by venue comparisons were also performed (no ban vs. partial ban vs. complete ban). Comparisons with previously collected data in 2006 when no ban was in place also was performed. Indoor air levels of PM(2.5) attributable to SHS dropped following the transition from a partial to a complete ban by 34% (137 μg/m(3) vs. 90 μg/m(3), p=0.003). This drop was larger in bars (from 195 μg/m(3) to 121 μg/m(3)), than in cafes (124 μg/m(3) vs. 87 μg/m(3)) or restaurants (42 μg/m(3) vs. 39 μg/m(3)). PM(2.5) concentrations between 2006 (no ban) and the partial ban of 2010 were also found to decrease by 94 μg/m(3); however, among matched venues, the levels of indoor air pollution were not found to change significantly (218 μg/m(3) vs. 178 μg/m(3), p=0.58). Comparing the 2010 complete ban results (n=120) with previously collected data from 2006 when no ban was in place (n=43), overall PM(2.5) concentrations were found to fall from 268 μg/m(3) to 89 μg/m(3), while a matched analysis found a significant reduction in PM(2.5) concentrations (249 μg/m(3) vs. 46 μg/m(3), p=0.011). The complete ban of smoking in hospitality venues in Greece led to a reduction in SHS exposure, in comparison to when the partial ban or no ban was in place; however, exposure to SHS was not eliminated indicating the need for stronger enforcement.

The influence of uncemented femoral stem length and design on its primary stability: a finite element analysis.

PubMed

Reimeringer, M; Nuño, N; Desmarais-Trépanier, C; Lavigne, M; Vendittoli, P A

2013-01-01

One of the crucial factors for short- and long-term clinical success of total hip arthroplasty cementless implants is primary stability. Indeed, motion at the bone-implant interface above 40 μm leads to partial bone ingrowth, while motion exceeding 150 μm completely inhibits bone ingrowth. The aim of this study was to investigate the effect of two cementless femoral stem designs with different lengths on the primary stability. A finite element model of a composite Sawbones(®) fourth generation, implanted with five lengths of the straight prosthesis design and four lengths of the curved prosthesis design, was loaded with hip joint and abductor forces representing two physiological activities: fast walking and stair climbing. We found that reducing the straight stem length from 146 to 54 mm increased the average micromotion from 17 to 52 μm during fast walking, while the peak value increased from 42 to 104 μm. With the curved stem, reducing length from 105 to 54 mm increased the average micromotion from 10 to 29 μm, while the peak value increased from 37 to 101 μm. Similar findings are obtained for stair climbing for both stems. Although the present study showed that femoral stem length as well as stem design directly influences its primary stability, for the two femoral stems tested, length could be reduced substantially without compromising the primary stability. With the aim of minimising surgical invasiveness, newer femoral stem design and currently well performing stems might be used with a reduced length without compromising primary stability and hence, long-term survivorship.

Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor

ClinicalTrials.gov

2016-10-19

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Biphenotypic Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Plasma Cell Neoplasms; Lymphoma; Hodgkin's Disease; Aplastic Anemia

Particle Filtering with Region-based Matching for Tracking of Partially Occluded and Scaled Targets*

PubMed Central

Nakhmani, Arie; Tannenbaum, Allen

2012-01-01

Visual tracking of arbitrary targets in clutter is important for a wide range of military and civilian applications. We propose a general framework for the tracking of scaled and partially occluded targets, which do not necessarily have prominent features. The algorithm proposed in the present paper utilizes a modified normalized cross-correlation as the likelihood for a particle filter. The algorithm divides the template, selected by the user in the first video frame, into numerous patches. The matching process of these patches by particle filtering allows one to handle the target’s occlusions and scaling. Experimental results with fixed rectangular templates show that the method is reliable for videos with nonstationary, noisy, and cluttered background, and provides accurate trajectories in cases of target translation, scaling, and occlusion. PMID:22506088

Learning Strategies in Matching to Sample: If-then and Configural Learning by Pigeons

PubMed Central

Katz, Jeffrey S.; Bodily, Kent D.; Wright, Anthony A.

2008-01-01

Pigeons learned a matching-to-sample task with a split training-set design in which half of the stimulus displays were untrained and tested following acquisition. Transfer to the untrained displays along with no novel-stimulus transfer indicated that these pigeons learned the task (partially) via if-then rules. Comparisons to other performance measures indicated that they also partially learned the task via configural learning (learning the gestalt of the whole stimulus display). Differences in the FR-sample requirement (1 vs. 20) had no systematic effect on the type of learning or level of learning obtained. Differences from a previous study (Wright, 1997) are discussed, including the effect of displaying the stimuli vertically (traditional display orientation) or horizontally from the floor. PMID:18079071

Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998-2006: a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group.

PubMed

Moore, Andrew S; Shaw, Peter J; Hallahan, Andrew R; Carter, Tina L; Kilo, Tatjana; Nivison-Smith, Ian; O'Brien, Tracey A; Tapp, Heather; Teague, Lochie; Wilson, Shaun R; Tiedemann, Karin

2009-02-02

To document haemopoietic stem cell transplantation (HSCT) activity and trends among paediatric patients in Australia and New Zealand. A retrospective analysis of data reported to the Australasian Bone Marrow Transplant Recipient Registry by the seven paediatric HSCT institutions in Australia and New Zealand over the 9-year period 1998-2006, with particular focus on the most recent years (2002-2006). Types of HSCT performed; transplant-related mortality (TRM); stem cell sources; indications for HSCT; causes of death after HSCT. Over the period 1998-2006, 522 autologous HSCT procedures (41%) and 737 allogeneic procedures (59%) were performed. About 60% of allogeneic transplants involved alternative donors (donors other than a human leukocyte antigen-matched sibling). The use of umbilical cord blood as a source of haemopoietic stem cells has doubled since 1998, with 34% of allogeneic transplants in 2006 using cord blood. Over the period 2002-2006, the median age of patients receiving transplants was 7 years (range, 0-19 years). The most common indications for allogeneic HSCT were acute lymphoblastic leukaemia (33%) and acute myeloid leukaemia (24%). The most common indications for autologous HSCT were neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). TRM at 1 year after transplant was 22% for alternative donor transplants, 7% for matched-sibling transplants and 5% for autologous transplants. Relapse or persistence of a child's underlying condition accounted for 54% of all deaths within 1 year after transplant. HSCT is an important procedure for children with a range of life-threatening illnesses. Local trends in the indications for HSCT, donor selection and TRM reflect contemporary international practice.

In delicate balance: stem cells and spinal cord injury advocacy.

PubMed

Parke, Sara; Illes, Judy

2011-09-01

Spinal cord injury (SCI) is a major focus for stem cell therapy (SCT). However, the science of SCT has not been well matched with an understanding of perspectives of persons with SCI. The online advocacy community is a key source of health information for primary stakeholders and their caregivers. In this study, we sought to characterize the content of SCI advocacy websites with respect to their discussion of SCT and stem cell tourism. We performed a comprehensive analysis of SCI advocacy websites identified through a web search and verified by expert opinion. Two independent researchers coded the information for major themes (e.g., scientific & clinical facts, research & funding, policy, ethics) and valence (positive, negative, balanced, neutral). Of the 40 SCI advocacy websites that met inclusion criteria, 50% (N=20) contained information about SCT. Less than 18% (N=7) contained information on stem cell tourism. There were more than ten times as many statements about SCT with a positive valence (N=67) as with a negative valence (N=6). Ethics-related SCT information comprised 20% (N=37) of the total content; the largest proportion of ethics-related content was devoted to stem cell tourism (80%, N=30 statements). Of those, the majority focused on the risks of stem cell tourism (N=16). Given the still-developing science behind SCT, the presence of cautionary information about stem cell tourism at advocacy sites is ethically appropriate. The absence of stem cell tourism information at the majority of advocacy sites represents a lost educational opportunity.

Partially deuterated potassium dihydrogen phosphate optimized for ultra-broadband optical parametric amplification

NASA Astrophysics Data System (ADS)

Fujioka, K.; Fujimoto, Y.; Tsubakimoto, K.; Kawanaka, J.; Shoji, I.; Miyanaga, N.

2015-03-01

The refractive index of a potassium dihydrogen phosphate (KDP) crystal strongly depends on the deuteration fraction of the crystal. The wavelength dependence of the phase-matching angle in the near-infrared optical parametric process shows convex and concave characteristics for pure KDP and pure deuterated KDP (DKDP), respectively, when pumped by the second harmonic of Nd- or Yb-doped solid state lasers. Using these characteristics, ultra-broadband phase matching can be realized by optimization of the deuteration fraction. The refractive index of DKDP that was grown with a different deuteration fraction (known as partially deuterated KDP or pDKDP) was measured over a wide wavelength range of 0.4-1.5 μm by the minimum deviation method. The wavelength dispersions of the measured refractive indices were fitted using a modified Sellmeier equation, and the deuteration fraction dependence was analyzed using the Lorentz-Lorenz equation. The wavelength-dependent phase-matching angle for an arbitrary deuteration fraction was then calculated for optical parametric amplification with pumping at a wavelength of 526.5 nm. The results revealed that a refractive index database with precision of more than 2 × 10-5 was necessary for exact evaluation of the phase-matching condition. An ultra-broad gain bandwidth of up to 490 nm will be feasible when using the 68% pDKDP crystal.

Exploring K-12 mathematics course progression: implications for collegiate success in Florida

NASA Astrophysics Data System (ADS)

Campbell, Bethany; Varney, Christopher; Wade, Aaron

Increasingly, Florida college students are pressured to change their major as few times as possible and take only required classes, all in order to ``Finish in Four, Save More''. If they fail to do so, they may be subject to penalties such as Excess Hour Fees. Partially as a result of this, students wishing to study STEM are at a significant disadvantage if they enter college unprepared to take calculus their first semester. We explore the various ``paths to success'' to STEM degrees, defined by entering college having taken calculus in high school, starting from fifth grade onwards.

Effect of Gibberellic Acid on the Plasticity and Elasticity of Avena Stem Segments 1

PubMed Central

Adams, Paul A.; Montague, Michael J.; Tepfer, Mark; Rayle, David L.; Ikuma, Hiroshi; Kaufman, Peter B.

1975-01-01

Extensibility characteristics of Avena stem segments treated with gibberellic acid (GA) were investigated in living internodes using a microgrowth method and in partially extracted cell walls subjected to Instron extensometer analysis. Both techniques showed that treatment with GA greatly increases internodal plasticity, but has virtually no effect on internodal elasticity. The increase in plasticity occurred 1 to 2 hours after the initiation of hormone treatment, which is similar to the time of onset of GA-enhanced growth and cell wall synthesis. Cycloheximide was shown to inhibit the effect of GA on plasticity. PMID:16659388

Correlated miR-mRNA expression signatures of mouse hematopoietic stem and progenitor cell subsets predict "Stemness" and "Myeloid" interaction networks.

PubMed

Heiser, Diane; Tan, Yee Sun; Kaplan, Ian; Godsey, Brian; Morisot, Sebastien; Cheng, Wen-Chih; Small, Donald; Civin, Curt I

2014-01-01

Several individual miRNAs (miRs) have been implicated as potent regulators of important processes during normal and malignant hematopoiesis. In addition, many miRs have been shown to fine-tune intricate molecular networks, in concert with other regulatory elements. In order to study hematopoietic networks as a whole, we first created a map of global miR expression during early murine hematopoiesis. Next, we determined the copy number per cell for each miR in each of the examined stem and progenitor cell types. As data is emerging indicating that miRs function robustly mainly when they are expressed above a certain threshold (∼100 copies per cell), our database provides a resource for determining which miRs are expressed at a potentially functional level in each cell type. Finally, we combine our miR expression map with matched mRNA expression data and external prediction algorithms, using a Bayesian modeling approach to create a global landscape of predicted miR-mRNA interactions within each of these hematopoietic stem and progenitor cell subsets. This approach implicates several interaction networks comprising a "stemness" signature in the most primitive hematopoietic stem cell (HSC) populations, as well as "myeloid" patterns associated with two branches of myeloid development.

HLA Engineering of Human Pluripotent Stem Cells

PubMed Central

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-01-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

HLA engineering of human pluripotent stem cells.

PubMed

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-06-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

PubMed Central

Gragert, Loren; Eapen, Mary; Williams, Eric; Freeman, John; Spellman, Stephen; Baitty, Robert; Hartzman, Robert; Rizzo, J. Douglas; Horowitz, Mary; Confer, Dennis; Maiers, Martin

2018-01-01

Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.) PMID:25054717

Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells.

PubMed

Liu, Ying; Giannopoulou, Eugenia G; Wen, Duancheng; Falciatori, Ilaria; Elemento, Olivier; Allis, C David; Rafii, Shahin; Seandel, Marco

2016-04-27

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of germ cell-specific gene expression and initiation of embryonic-like programs. Furthermore, SSCs in vitro maintain the epigenomic characteristics of germ cells in vivo. Our observations suggest that SSCs encode innate plasticity through the epigenome and that both conversion of promoter chromatin states and activation of cell type-specific enhancers are prominent features of reprogramming.

Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells

PubMed Central

Liu, Ying; Giannopoulou, Eugenia G.; Wen, Duancheng; Falciatori, Ilaria; Elemento, Olivier; Allis, C. David; Rafii, Shahin; Seandel, Marco

2016-01-01

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of germ cell-specific gene expression and initiation of embryonic-like programs. Furthermore, SSCs in vitro maintain the epigenomic characteristics of germ cells in vivo. Our observations suggest that SSCs encode innate plasticity through the epigenome and that both conversion of promoter chromatin states and activation of cell type-specific enhancers are prominent features of reprogramming. PMID:27117588

Drosophila Perlecan Regulates Intestinal Stem Cell Activity via Cell-Matrix Attachment

PubMed Central

You, Jia; Zhang, Yan; Li, Zhouhua; Lou, Zhefeng; Jin, Longjin; Lin, Xinhua

2014-01-01

Summary Stem cells require specialized local microenvironments, termed niches, for normal retention, proliferation, and multipotency. Niches are composed of cells together with their associated extracellular matrix (ECM). Currently, the roles of ECM in regulating niche functions are poorly understood. Here, we demonstrate that Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut. Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach from underlying ECM, lose their identity, and fail to proliferate. These defects are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity but partially depend on integrin signaling activity. We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche. PMID:24936464

Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform

NASA Astrophysics Data System (ADS)

Müller, Eike; Wang, Weijia; Qiao, Wenlian; Bornhäuser, Martin; Zandstra, Peter W.; Werner, Carsten; Pompe, Tilo

2016-08-01

Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.

The Influence Of Team Rating On Running Performance In Elite Gaelic Football.

PubMed

Mangan, Shane; Malone, Shane; Ryan, Martin; Gahan, Jason Mc; Warne, Joe; Martin, Denise; O'Neill, Cian; Burns, Con; Collins, Kieran

2017-11-06

It is currently unknown how team rating influences running performance in Gaelic football. GPS technologies were used to quantify match-running performance within 5 elite Gaelic football teams over a period of 5 years (2012-2016). In total 780 player data sets were collected over 95 matches. Running performance variables included total distance, high-speed distance (≥17 km h) and the percentage of high-speed distance. Team ratings were determined objectively using the Elo Ratings System for Gaelic football. Reference team rating had trivial effects on total distance (p = 0.011, partial η2 = 0.008) and high-speed distance (p = 0.011, partial η2 = 0.008). Opposition team rating had small effects on total distance (p = 0.005, partial η2 = 0.016) and high-speed distance (p = 0.001, partial η2 = 0.020). Top tier teams cover greater total distances and high-speed distance than lower tier teams. Players cover considerably less total distance and high-speed distance against tier 3 and tier 4 teams. Tier 1 players ran a significantly higher percentage of distance at high-speed, than players who played for tier 2 teams (p = 0.020). The competitive advantage of top tier Gaelic football teams is closely linked with their ability to demonstrate a higher physical intensity than lower tier teams.

Reconstruction-Based Digital Dental Occlusion of the Partially Edentulous Dentition.

PubMed

Zhang, Jian; Xia, James J; Li, Jianfu; Zhou, Xiaobo

2017-01-01

Partially edentulous dentition presents a challenging problem for the surgical planning of digital dental occlusion in the field of craniomaxillofacial surgery because of the incorrect maxillomandibular distance caused by missing teeth. We propose an innovative approach called Dental Reconstruction with Symmetrical Teeth (DRST) to achieve accurate dental occlusion for the partially edentulous cases. In this DRST approach, the rigid transformation between two symmetrical teeth existing on the left and right dental model is estimated through probabilistic point registration by matching the two shapes. With the estimated transformation, the partially edentulous space can be virtually filled with the teeth in its symmetrical position. Dental alignment is performed by digital dental occlusion reestablishment algorithm with the reconstructed complete dental model. Satisfactory reconstruction and occlusion results are demonstrated with the synthetic and real partially edentulous models.

Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.

PubMed

Dalianis, Tina; Ljungman, Per

2011-03-01

BK virus (BKV)-associated hemorrhagic cystitis (HC), varying from mild hematuria with or without dysuria to life-threating bleeding and clots that may cause urinary obstruction and renal failure, causes significant morbidity and mortality in haematopoetic stem cell transplanted (HSCT) patients. Unfortunately, its development is difficult to predict since BK viruria is very common after HSCT and can be present in patients with and without HC. There is therefore the need to identify risk factors that may increase the risk of developing HC after HSCT. The viral load of BK-viruria, as well as BK viremia, has been monitored for this purpose. Moreover, having full myeoblative conditioning (MC) versus reduced intensity conditioning (RIC) prior to HSCT and an HLA-matched or -mismatched graft from an unrelated donor in contrast to an HLA-matched graft from a related donor have been studied as risk factors for HC. In addition, graft versus host disease has been examined, but has not been defined as a definite risk factor for HC. We conclude that the present evidence suggests that HSCT patients with BK viruria, receiving MC and an unrelated donor graft that is HLA-mismatched have an increased risk for developing HC in comparison to patients receiving RIC and an HLA-matched related donor graft.

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

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

Ali, Haytham; Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University; Galal, Omima

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days inmore » sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.« less

Adjuvant Everolimus for Resected Kidney Cancer

Cancer.gov

In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

Stochastic reservoir simulation for the modeling of uncertainty in coal seam degasification

PubMed Central

Karacan, C. Özgen; Olea, Ricardo A.

2018-01-01

Coal seam degasification improves coal mine safety by reducing the gas content of coal seams and also by generating added value as an energy source. Coal seam reservoir simulation is one of the most effective ways to help with these two main objectives. As in all modeling and simulation studies, how the reservoir is defined and whether observed productions can be predicted are important considerations. Using geostatistical realizations as spatial maps of different coal reservoir properties is a more realistic approach than assuming uniform properties across the field. In fact, this approach can help with simultaneous history matching of multiple wellbores to enhance the confidence in spatial models of different coal properties that are pertinent to degasification. The problem that still remains is the uncertainty in geostatistical simulations originating from the partial sampling of the seam that does not properly reflect the stochastic nature of coal property realizations. Stochastic simulations and using individual realizations, rather than E-type, make evaluation of uncertainty possible. This work is an advancement over Karacan et al. (2014) in the sense of assessing uncertainty that stems from geostatistical maps. In this work, we batched 100 individual realizations of 10 coal properties that were randomly generated to create 100 bundles and used them in 100 separate coal seam reservoir simulations for simultaneous history matching. We then evaluated the history matching errors for each bundle and defined the single set of realizations that would minimize the error for all wells. We further compared the errors with those of E-type and the average realization of the best matches. Unlike in Karacan et al. (2014), which used E-type maps and average of quantile maps, using these 100 bundles created 100 different history match results from separate simulations, and distributions of results for in-place gas quantity, for example, from which uncertainty in coal property realizations could be evaluated. The study helped to determine the realization bundle that consisted of the spatial maps of coal properties, which resulted in minimum error. In addition, it was shown that both E-type and the average of realizations that gave the best match for invidual approximated the same properties resonably. Moreover, the determined realization bundle showed that the study field initially had 151.5 million m3 (cubic meter) of gas and 1.04 million m3 water in the coal, corresponding to Q90 of the entire range of probability for gas and close to Q75 for water. In 2013, in-place fluid amounts decreased to 138.9 million m3 and 0.997 million m3 for gas and water, respectively. PMID:29563647

Controlling Seizures

ERIC Educational Resources Information Center

Henderson, Nancy

2008-01-01

This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

DTIC Science & Technology

2012-10-01

Hyperalgesia and Mechanical Allodynia by Curcumin in a Rat Model of Partial Thickness Thermal Injury Clifford, John Evaluation Of A Non-Invasive System Of...Thermal Injury Garza, Thomas Biochemical Correlates for the Analgesic Action Of Curcumin : A Naturally occurring Anti-inflammatory Agent Greer, Angie

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.

Pragmatic hydraulic theory predicts stomatal responses to climatic water deficits.

PubMed

Sperry, John S; Wang, Yujie; Wolfe, Brett T; Mackay, D Scott; Anderegg, William R L; McDowell, Nate G; Pockman, William T

2016-11-01

Ecosystem models have difficulty predicting plant drought responses, partially from uncertainty in the stomatal response to water deficits in soil and atmosphere. We evaluate a 'supply-demand' theory for water-limited stomatal behavior that avoids the typical scaffold of empirical response functions. The premise is that canopy water demand is regulated in proportion to threat to supply posed by xylem cavitation and soil drying. The theory was implemented in a trait-based soil-plant-atmosphere model. The model predicted canopy transpiration (E), canopy diffusive conductance (G), and canopy xylem pressure (P canopy ) from soil water potential (P soil ) and vapor pressure deficit (D). Modeled responses to D and P soil were consistent with empirical response functions, but controlling parameters were hydraulic traits rather than coefficients. Maximum hydraulic and diffusive conductances and vulnerability to loss in hydraulic conductance dictated stomatal sensitivity and hence the iso- to anisohydric spectrum of regulation. The model matched wide fluctuations in G and P canopy across nine data sets from seasonally dry tropical forest and piñon-juniper woodland with < 26% mean error. Promising initial performance suggests the theory could be useful in improving ecosystem models. Better understanding of the variation in hydraulic properties along the root-stem-leaf continuum will simplify parameterization. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Childhood Hematopoietic Cell Transplantation (PDQ®)—Health Professional Version

Cancer.gov

Hematopoietic cell transplantation involves the infusion of blood stem cells (peripheral/umbilical cord blood, bone marrow) into a patient to reconstitute the blood system. Get detailed information about autologous and allogeneic transplant, including cell selection, HLA matching, and preparative regimens, and the acute complications and late effects of treatment in this summary for clinicians.

The Impact of Undergraduate Debt on the Graduate School Enrollment of STEM Baccalaureates

ERIC Educational Resources Information Center

Malcom, Lindsey E.; Dowd, Alicia C.

2012-01-01

While student loans provide college opportunity for many, undergraduate student debt resulting from typical and heavy borrowing hinders future investments in human capital. Propensity score matching analysis of the NSF's 2003 National Survey of Recent College Graduates demonstrates that debt negatively affects the graduate school enrollment of…

Steps towards Collective Sustainability in Biomedical Research.

PubMed

Salvetti, Marco; Lubetzki, Catherine; Kapoor, Raj; Ristori, Giovanni; Costa, Ericka; Battaglia, Mario A; Andreaus, Michele; Abbracchio, Maria Pia; Matarese, Giuseppe; Zaratin, Paola

2018-05-01

The optimism surrounding multistakeholder research initiatives does not match the clear view of policies that are needed to exploit the potential of these collaborations. Here we propose some action items that stem from the integration between research advancements with the perspectives of patient-advocacy organizations, academia, and industry. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Role of Prototype Matching in Science Pursuits: Perceptions of Scientists That Are Inaccurate and Diverge From Self-Perceptions Predict Reduced Interest in a Science Career.

PubMed

McPherson, Erin; Park, Bernadette; Ito, Tiffany A

2018-06-01

Self-to-prototype matching is a strategy of mental comparisons between the self-concept and the typical or "representative" member of a group to make some judgment. Such a process might contribute to interest in pursuing a science career and, relatedly, women's underrepresentation in physical science, technology, engineering, and mathematics (pSTEM) fields. Across four studies, we measured self-scientist discrepancies on communal, agentic, and scientific dimensions, and assessed participants' interest in a science career. The most consistent predictor of science interest was the discrepancy between self and scientist on the scientific dimension (e.g., intelligent, meticulous). Study 4 established that students with larger self-scientist discrepancies also had less accurate perceptions of students pursuing science, and that inaccuracy was related to lower science interest. Thus, students with lower science interest do not just perceive scientists differently from themselves but also erroneously. Discrepancy and inaccuracy together explained a significant portion of the gender gap in pSTEM interest.

DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation

PubMed Central

LI, YA-TING; XIE, MING-KUN; WU, JIN

2014-01-01

Allogeneic peripheral blood stem cells transplantation (allo-PBSCT) or allogeneic bone marrow transplantation (allo-BMT) have been widely used to treat patients exhibiting certain severe illnesses. However, previous studies have shown that the biological materials of allo-PBSCT or allo-BMT recipients may not constitute credible materials for personal identification. In the present study, four types of commonly used samples were collected from a male individual following gender-matched allo-BMT. Autosomal short tandem repeat (STR) and Y-STR markers analysis, based on polymerase chain reaction, were used to evaluate the chimerism status. The results showed that the blood sample were all donor type, the buccal swab sample were mixed chimerism, and the sperm and hair follicle samples maintained a recipient origin of 100%. In conclusion, identical results were obtained by the two methods and it was confirmed that DNA extracted from hair follicles and sperm can be used as a reference for the pre-transplant genotype DNA profile of the recipient in the gender-match allo-BMT or -PBSCT. PMID:25279149

Through the eyes of young sibling donors: the hematopoietic stem cell donation experience.

PubMed

D'Auria, Jennifer P; Fitzgerald, Tania M; Presler, Cammie M; Kasow, Kimberly A

2015-01-01

This qualitative study used a grounded theory approach to explore how pediatric sibling donors of a successful hematopoietic stem cell transplantation conceptualized their donation experiences. Saving my sister's (or brother's) life describes the central phenomenon identified by this purposive sample of 8 sibling donors. Five themes captured their memories: being the perfect match, stepping up, worrying about the outcome, the waiting process, and sharing a special bond. Further research surrounding changes in relational issues will provide insight into inter-sibling support and the developmental course of the sibling relationship into adulthood when intensified by a health crisis. Copyright © 2015 Elsevier Inc. All rights reserved.

Examining Thai high school students' developing STEM projects

NASA Astrophysics Data System (ADS)

Teenoi, Kultida; Siripun, Kulpatsorn; Yuenyong, Chokchai

2018-01-01

Like others, Thailand education strongly focused on STEM education. This paper aimed to examine existing Thai high school students' integrated knowledge about science, technology, engineering, and mathematics (STEM) in their developing science project. The participants included 49 high school students were studying the subject of individual study (IS) in Khon Kaen wittayayon school, Khon Kaen, Thailand. The IS was provided to gradually enhance students to know how to do science project starting from getting start to do science projects, They enrolled to study the individual study of science project for three year in roll. Methodology was qualitative research. Views of students' integrated knowledge about STEM were interpreted through participant observation, interview, and students' science projects. The first author as participant observation has taught this group of students for 3 years. It found that 16 science projects were developed. Views of students' integrated knowledge about STEM could be categorized into three categories. These included (1) completely indicated integration of knowledge about science, technology, engineering, and mathematics, (2) partial indicated integration of knowledge about science, technology, engineering, and mathematics, and (3) no integration. The findings revealed that majority of science projects could be categorized as completely indicated integration of knowledge about science, technology, engineering, and mathematics. The paper suggested some ideas of enhancing students to applying STEM for developing science projects.

Tree water relations can trigger monoterpene emissions from Scots pine stems during spring recovery

NASA Astrophysics Data System (ADS)

Vanhatalo, A.; Chan, T.; Aalto, J.; Korhonen, J. F.; Kolari, P.; Hölttä, T.; Nikinmaa, E.; Bäck, J.

2015-09-01

Tree canopies are known to emit large amounts of VOCs (volatile organic compounds) such as monoterpenes into the surrounding air. High VOC emission rates from boreal forests have been observed during the transition from winter to summer activity. The most important sources of these are considered to be the green foliage, understory vegetation and soil organisms, but emissions from the living stand woody compartments have so far not been quantified. We analyzed whether the non-foliar components could partially explain the springtime high emission rates. We measured the monoterpene emissions from Scots pine (Pinus sylvestris L.) stem and shoots during the dehardening phase of trees in field conditions in two consecutive springs. We observed a large, transient monoterpene burst from the stem, while the shoot monoterpene emissions remained low. The burst lasted about 12 h. Simultaneously, an unusual nighttime sap flow and a non-systematic diurnal pattern of tree diameter were detected. Hence, we suggest that the monoterpene burst was a consequence of the recovery of the stem from wintertime, and likely related to the refilling of embolized tracheids and/or phenological changes in the living cells of the stem. This indicates that the dominant processes and environmental drivers triggering the monoterpene emissions are different between the stem and the foliage.

Emodin suppresses maintenance of stemness by augmenting proteosomal degradation of epidermal growth factor receptor/epidermal growth factor receptor variant III in glioma stem cells.

PubMed

Kim, Jeongyub; Lee, Jong-Seon; Jung, Jieun; Lim, Inhye; Lee, Ji-Yun; Park, Myung-Jin

2015-02-01

There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs.

Aspen height, stem-girth and survivorship in an area of high ungulate use

USGS Publications Warehouse

Keigley, R.B.; Frisina, M.R.

2008-01-01

An increase in ungulate population size potentially exposes aspen suckers, saplings, and trees to increased use. This study examined how stem height and girth influenced the selection of stems by ungulates for browsing, rubbing, and gnawing, and reconstructed the history of ungulate use for the study area. Transects were run through each of three aspen clones growing in southwestern Montana to determine height, circumference, and the surface area from which bark was totally and partially removed by rubbing and gnawing. Stems 20-250 cm tall were browsed. Stems 2-13 cm diameter were preferentially selected for rubbing and gnawing. The area of totally removed bark on dead saplings was twice the area of removed bark on live stems of similar diameter, suggesting that bark removal played a major role in the death of some stems. Based on an analysis of stem height and age, ungulate browsing was inferred to have increased from a light-to-moderate level to an intense level in 1991. The depth of scars was used to date scarring events. An increase in rubbing and gnawing was determined to have occurred about 1985. We concluded that elk were primarily responsible for the observed impacts. The combined effect of rubbing, gnawing, and browsing affects a broader span of ages compared to the effect of browsing alone. If prescribed fire is used to rejuvenate aspen stands, the resulting young stems should be protected from heavy browsing, rubbing and gnawing until they reach about 13 cm diameter and have grown out of the browse zone.

Subgrain boundary analyses in deformed orthopyroxene by TEM/STEM with EBSD-FIB sample preparation technique

NASA Astrophysics Data System (ADS)

Kogure, Toshihiro; Raimbourg, Hugues; Kumamoto, Akihito; Fujii, Eiko; Ikuhara, Yuichi

2014-12-01

High-resolution structure analyses using electron beam techniques have been performed for the investigation of subgrain boundaries (SGBs) in deformed orthopyroxene (Opx) in mylonite from Hidaka Metamorphic Belt, Hokkaido, Japan, to understand ductile deformation mechanism of silicate minerals in shear zones. Scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD) analysis of Opx porphyroclasts in the mylonitic rock indicated that the crystal orientation inside the Opx crystals gradually changes by rotation about the b-axis by SGBs and crystal folding. In order to observe the SGBs along the b-axis by transmission electron microscopy (TEM) or scanning TEM (STEM), the following sample preparation protocol was adopted. First, petrographic thin sections were slightly etched with hydrofluoric acid to identify SGBs in SEM. The Opx crystals whose b-axes were oriented close to the normal of the surface were identified by EBSD, and the areas containing SGBs were picked and thinned for (S) TEM analysis with a focused ion beam instrument with micro-sampling system. High-resolution TEM imaging of the SGBs in Opx revealed various boundary structures from a periodic array of dissociated (100) [001] edge dislocations to partially or completely incoherent crystals, depending on the misorientation angle. Atomic-resolution STEM imaging clearly confirmed the formation of clinopyroxene (Cpx) structure between the dissociated partial dislocations. Moreover, X-ray microanalysis in STEM revealed that the Cpx contains a considerable amount of calcium replacing iron. Such chemical inhomogeneity may limit glide motion of the dislocation and eventually the plastic deformation of the Opx porphyroclasts at a low temperature. Chemical profiles across the high-angle incoherent SGB also showed an enrichment of the latter in calcium at the boundary, suggesting that SGBs are an efficient diffusion pathway of calcium out of host Opx grain during cooling.

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

PubMed

Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

2013-03-15

This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

A digital matched filter for reverse time chaos

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

Bailey, J. Phillip, E-mail: mchamilton@auburn.edu; Beal, Aubrey N.; Dean, Robert N.

2016-07-15

The use of reverse time chaos allows the realization of hardware chaotic systems that can operate at speeds equivalent to existing state of the art while requiring significantly less complex circuitry. Matched filter decoding is possible for the reverse time system since it exhibits a closed form solution formed partially by a linear basis pulse. Coefficients have been calculated and are used to realize the matched filter digitally as a finite impulse response filter. Numerical simulations confirm that this correctly implements a matched filter that can be used for detection of the chaotic signal. In addition, the direct form ofmore » the filter has been implemented in hardware description language and demonstrates performance in agreement with numerical results.« less

Natural Hypolignification Is Associated with Extensive Oligolignol Accumulation in Flax Stems1[C][W

PubMed Central

Huis, Rudy; Morreel, Kris; Fliniaux, Ophélie; Lucau-Danila, Anca; Fénart, Stéphane; Grec, Sébastien; Neutelings, Godfrey; Chabbert, Brigitte; Mesnard, François; Boerjan, Wout; Hawkins, Simon

2012-01-01

Flax (Linum usitatissimum) stems contain cells showing contrasting cell wall structure: lignified in inner stem xylem tissue and hypolignified in outer stem bast fibers. We hypothesized that stem hypolignification should be associated with extensive phenolic accumulation and used metabolomics and transcriptomics to characterize these two tissues. 1H nuclear magnetic resonance clearly distinguished inner and outer stem tissues and identified different primary and secondary metabolites, including coniferin and p-coumaryl alcohol glucoside. Ultrahigh-performance liquid chromatography-Fourier transform ion cyclotron resonance-mass spectrometry aromatic profiling (lignomics) identified 81 phenolic compounds, of which 65 were identified, to our knowledge, for the first time in flax and 11 for the first time in higher plants. Both aglycone forms and glycosides of monolignols, lignin oligomers, and (neo)lignans were identified in both inner and outer stem tissues, with a preponderance of glycosides in the hypolignified outer stem, indicating the existence of a complex monolignol metabolism. The presence of coniferin-containing secondary metabolites suggested that coniferyl alcohol, in addition to being used in lignin and (neo)lignan formation, was also utilized in a third, partially uncharacterized metabolic pathway. Hypolignification of bast fibers in outer stem tissues was correlated with the low transcript abundance of monolignol biosynthetic genes, laccase genes, and certain peroxidase genes, suggesting that flax hypolignification is transcriptionally regulated. Transcripts of the key lignan genes Pinoresinol-Lariciresinol Reductase and Phenylcoumaran Benzylic Ether Reductase were also highly abundant in flax inner stem tissues. Expression profiling allowed the identification of NAC (NAM, ATAF1/2, CUC2) and MYB transcription factors that are likely involved in regulating both monolignol production and polymerization as well as (neo)lignan production. PMID:22331411

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions.

PubMed

Kumar, Rajat; Kimura, Fumihiko; Ahn, Kwang Woo; Hu, Zhen-Huan; Kuwatsuka, Yachiyo; Klein, John P; Pasquini, Marcelo; Miyamura, Koichi; Kato, Koji; Yoshimi, Ayami; Inamoto, Yoshihiro; Ichinohe, Tatsuo; Wood, William Allen; Wirk, Baldeep; Seftel, Matthew; Rowlings, Philip; Marks, David I; Schultz, Kirk R; Gupta, Vikas; Dedeken, Laurence; George, Biju; Cahn, Jean-Yves; Szer, Jeff; Lee, Jong Wook; Ho, Aloysius Y L; Fasth, Anders; Hahn, Theresa; Khera, Nandita; Dalal, Jignesh; Bonfim, Carmem; Aljurf, Mahmoud; Atsuta, Yoshiko; Saber, Wael

2016-05-01

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States-Canada (n = 486) and other HIC (n = 1264); upper middle income (UMIC) (n = 482); and combined lower-middle, low-income countries (LM-LIC) (n = 142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC (P < .001). There was no significant difference in OS between BM and PBSCs in UMIC (P = .32) or LM-LIC (P = .23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P = .002). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

PubMed

Bleyzac, N; Cuzzubbo, D; Rénard, C; Garnier, N; Dubois, V; Domenech, C; Goutagny, M-P; Plesa, A; Grardel, N; Goutelle, S; Janoly-Duménil, A; Bertrand, Y

2016-05-01

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

CMV-specific immune reconstitution following allogeneic stem cell transplantation

PubMed Central

Blyth, Emily; Withers, Barbara; Clancy, Leighton; Gottlieb, David

2016-01-01

ABSTRACT Cytomegalovirus (CMV) remains a major contributor to morbidity and mortality following allogeneic haemopoietic stem cell transplant (HSCT) despite widespread use of viraemia monitoring and pre-emptive antiviral therapy. Uncontrolled viral replication occurs primarily in the first 100 d post transplant but this high risk period can extend to many months if immune recovery is delayed. The re-establishment of a functional population of cellular effectors is essential for control of virus replication and depends on recipient and donor serostatus, the stem cell source, degree of HLA matching and post-transplant factors such as CMV antigen exposure, presence of GVHD and ongoing use of immune suppression. A number of immune monitoring assays exist but have not yet become widely accessible for routine clinical use. Vaccination, adoptive transfer of CMV specific T cells and a number of graft engineering processes are being evaluated to enhance of CMV specific immune recovery post HSCT. PMID:27580355

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Anemia

PubMed Central

Lucarelli, Guido; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid

2012-01-01

The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class–based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation. PMID:22553502

Computer algorithms in the search for unrelated stem cell donors.

PubMed

Steiner, David

2012-01-01

Hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow. A lot of patients have no suitable HLA-matched donor within their family, so physicians must activate a "donor search process" by interacting with national and international donor registries who will search their databases for adult unrelated donors or cord blood units (CBU). Information and communication technologies play a key role in the donor search process in donor registries both nationally and internationaly. One of the major challenges for donor registry computer systems is the development of a reliable search algorithm. This work discusses the top-down design of such algorithms and current practice. Based on our experience with systems used by several stem cell donor registries, we highlight typical pitfalls in the implementation of an algorithm and underlying data structure.

An analysis of the therapeutic benefits of genotyping in pediatric hematopoietic stem cell transplantation.

PubMed

Wright, Felicity A; Bebawy, Mary; O'Brien, Tracey A

2015-01-01

Hematopoietic stem cell transplantation is a high-risk procedure that is offered, with curative intent, to patients with malignant and nonmalignant disease. The clinical benefits of personalization of therapy by genotyping have been demonstrated by the reduction in transplant related mortality from donor-recipient HLA matching. However, defining the relationship between genotype and transplant conditioning agents is yet to be translated into clinical practice. A number of the therapeutic agents used in stem cell transplant preparative regimens have pharmacokinetic parameters that predict benefit of incorporating pharmacogenomic data into dosing strategies. Busulfan, cyclophosphamide, thio-TEPA and etoposide have well-described drug metabolism pathways, however candidate gene studies have identified there is a gap in the identification of pharmacogenomic data that can be used to improve transplant outcomes. Incorporating pharmacogenomics into pharmacokinetic modeling may demonstrate the therapeutic benefits of genotyping in transplant preparative regimen agents.

Natural cellulose fibers from switchgrass with tensile properties similar to cotton and linen.

PubMed

Reddy, Narendra; Yang, Yiqi

2007-08-01

We report the production and characteristics of natural cellulose fibers obtained from the leaves and stems of switchgrass. In this paper, the composition, structure and properties of fibers obtained from the leaves and stem of switchgrass have been studied in comparison to the common natural cellulose fibers, such as cotton, linen and kenaf. The leaves and stems of switchgrass have tensile properties intriguingly similar to that of linen and cotton, respectively. Fibers were obtained from the leaves and stems of switchgrass using a simple alkaline extraction and the structure and properties of the fibers were studied. Fibers obtained from switchgrass leaves have crystallinity of 51%, breaking tenacity of 5.5 g per denier (715 MPa) and breaking elongation of 2.2% whereas the corresponding values for fibers obtained from switchgrass stems are 46%, 2.7 g per denier and 6.8%, respectively. Switchgrass is a relatively easy to grow and high yield biomass crop that can be source to partially substitute the natural and synthetic fibers currently in use. We hope that this research will stimulate interests in using switchgrass as a novel fiber crop in addition to being promoted as a potential source for biofuels. (c) 2007 Wiley Periodicals, Inc.

[Stem cell-based cardiac regeneration after myocardial infarction].

PubMed

Reinsch, M; Weinberger, F

2018-03-01

Myocardial infarction leads to an irreversible loss of vital myocardial cells. The transplantation of new cardiomyocytes into the heart was first described over 20 years ago and represents a straightforward approach to remuscularize a damaged heart. Due to the lack of human cells a clinical application seemed ambitious; however, dramatic progress in stem cell biology over the last two decades has paved the way towards a clinical application. This is especially important as the prognosis for patients with terminal heart failure is still poor. The transplantation of either cardiomyocytes or engineered heart tissue derived from pluripotent stem cells (either embryonic stem cells or induced pluripotent stem cells) might represent a new regenerative approach. Transplantation of either cells or tissue constructs has now been evaluated in several preclinical models, which have demonstrated that an injured heart can be (partially) remuscularized; however, major hurdles towards a clinical application are the transplantation-related occurrence of arrhythmia, the potential tumorigenicity of pluripotent cells and the required immunosuppression. Several groups are working hard to solve these problems and we are optimistic that the first clinical studies will take place within the next few years.

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal.

PubMed

Sun, Zhao; Yu, Wenjie; Sanz Navarro, Maria; Sweat, Mason; Eliason, Steven; Sharp, Thad; Liu, Huan; Seidel, Kerstin; Zhang, Li; Moreno, Myriam; Lynch, Thomas; Holton, Nathan E; Rogers, Laura; Neff, Traci; Goodheart, Michael J; Michon, Frederic; Klein, Ophir D; Chai, Yang; Dupuy, Adam; Engelhardt, John F; Chen, Zhi; Amendt, Brad A

2016-11-15

Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development. © 2016. Published by The Company of Biologists Ltd.

Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

PubMed

Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J; Zerfass, Christina; Senner, Volker; Ehrlich, Marc; Psathaki, Olympia E; Han, Dong Wook; Tapia, Natalia; Zaehres, Holm; Schöler, Hans R; Kuhlmann, Tanja; Hargus, Gunnar

2016-05-01

Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs. Copyright © 2016 Roslin Cells Ltd. Published by Elsevier B.V. All rights reserved.

An "age"-structured model of hematopoietic stem cell organization with application to chronic myeloid leukemia.

PubMed

Roeder, Ingo; Herberg, Maria; Horn, Matthias

2009-04-01

Previously, we have modeled hematopoietic stem cell organization by a stochastic, single cell-based approach. Applications to different experimental systems demonstrated that this model consistently explains a broad variety of in vivo and in vitro data. A major advantage of the agent-based model (ABM) is the representation of heterogeneity within the hematopoietic stem cell population. However, this advantage comes at the price of time-consuming simulations if the systems become large. One example in this respect is the modeling of disease and treatment dynamics in patients with chronic myeloid leukemia (CML), where the realistic number of individual cells to be considered exceeds 10(6). To overcome this deficiency, without losing the representation of the inherent heterogeneity of the stem cell population, we here propose to approximate the ABM by a system of partial differential equations (PDEs). The major benefit of such an approach is its independence from the size of the system. Although this mean field approach includes a number of simplifying assumptions compared to the ABM, it retains the key structure of the model including the "age"-structure of stem cells. We show that the PDE model qualitatively and quantitatively reproduces the results of the agent-based approach.

Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

PubMed

Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

2015-12-01

Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer. ©2015 American Association for Cancer Research.

Estimation of size of cord blood inventory based on high-resolution typing of HLAs.

PubMed

Song, E Y; Huh, J Y; Kim, S Y; Kim, T G; Oh, S; Yoon, J H; Roh, E Y; Park, M H; Kang, M S; Shin, S

2014-07-01

Methods for estimating the cord blood (CB) inventory size required vary according to the ethnic diversity of the HLA, degree of HLA matching and HLA-typing resolution. We estimated the CB inventory size required using 7190 stored CB units (CBU) and 2450 patients who were awaiting or underwent allogeneic hematopoietic stem cell transplantation. With high-resolution typing of HLA-A, B and DRB1, 94.6% of Korean patients could find CBUs in 100 000 CBUs with a 5/6 match, and 95.7% could find CBUs in 5000 CBUs with a 4/6 match. With low-resolution typing of HLA-A and B and high-resolution typing of leukocyte antigen-DRB1, 95% of patients could find CBUs in 50 000 CBUs with a 5/6 match, and 96.7% could find CBUs in 3000 CBUs  with a 4/6 match. With additional high-resolution typing for HLA-A and B, which could improve transplantation outcome, the size of the CB inventory would need to increase twofold for Koreans.

Reconstruction-based Digital Dental Occlusion of the Partially Edentulous Dentition

PubMed Central

Zhang, Jian; Xia, James J.; Li, Jianfu; Zhou, Xiaobo

2016-01-01

Partially edentulous dentition presents a challenging problem for the surgical planning of digital dental occlusion in the field of craniomaxillofacial surgery because of the incorrect maxillomandibular distance caused by missing teeth. We propose an innovative approach called Dental Reconstruction with Symmetrical Teeth (DRST) to achieve accurate dental occlusion for the partially edentulous cases. In this DRST approach, the rigid transformation between two symmetrical teeth existing on the left and right dental model is estimated through probabilistic point registration by matching the two shapes. With the estimated transformation, the partially edentulous space can be virtually filled with the teeth in its symmetrical position. Dental alignment is performed by digital dental occlusion reestablishment algorithm with the reconstructed complete dental model. Satisfactory reconstruction and occlusion results are demonstrated with the synthetic and real partially edentulous models. PMID:26584502

Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

PubMed Central

Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

2014-01-01

Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening.

PubMed

O'Duibhir, Eoghan; Carragher, Neil O; Pollard, Steven M

2017-04-01

Patients diagnosed with glioblastoma (GBM) continue to face a bleak prognosis. It is critical that new effective therapeutic strategies are developed. GBM stem cells have molecular hallmarks of neural stem and progenitor cells and it is possible to propagate both non-transformed normal neural stem cells and GBM stem cells, in defined, feeder-free, adherent culture. These primary stem cell lines provide an experimental model that is ideally suited to cell-based drug discovery or genetic screens in order to identify tumour-specific vulnerabilities. For many solid tumours, including GBM, the genetic disruptions that drive tumour initiation and growth have now been catalogued. CRISPR/Cas-based genome editing technologies have recently emerged, transforming our ability to functionally annotate the human genome. Genome editing opens prospects for engineering precise genetic changes in normal and GBM-derived neural stem cells, which will provide more defined and reliable genetic models, with critical matched pairs of isogenic cell lines. Generation of more complex alleles such as knock in tags or fluorescent reporters is also now possible. These new cellular models can be deployed in cell-based phenotypic drug discovery (PDD). Here we discuss the convergence of these advanced technologies (iPS cells, neural stem cell culture, genome editing and high content phenotypic screening) and how they herald a new era in human cellular genetics that should have a major impact in accelerating glioblastoma drug discovery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

3D Graphene Oxide-encapsulated Gold Nanoparticles to Detect Neural Stem Cell Differentiation

PubMed Central

Kim, Tae-Hyung; Lee, Ki-Bum; Choi, Jeong-Woo

2013-01-01

Monitoring of stem cell differentiation and pluripotency is an important step for the practical use of stem cells in the field of regenerative medicine. Hence, a new non-destructive detection tool capable of in situ monitoring of stem cell differentiation is highly needed. In this study, we report a 3D graphene oxide-encapsulated gold nanoparticle that is very effective for the detection of the differentiation potential of neural stem cells (NSCs) based on surface-enhanced Raman spectroscopy (SERS). A new material, 3D GO-encapsulated gold nanoparticle, is developed to induce the double enhancement effect of graphene oxide and gold nanoparticle on SERS signals which is only effective for undifferentiated NSCs. The Raman peaks achieved from undifferentiated NSCs on the graphene oxide (GO)-encapsulated gold nanoparticles were 3.5 times higher than peaks obtained from normal metal structures and were clearly distinguishable from those of differentiated cells. The number of C=C bonds and the raman instensity at 1656cm−1 was found to show a positive correlation, which matches the differentiation state of the NSCs. Moreover, the substrate composed of 3D GO-encapsulated gold nanoparticles was also effective at distinguishing the differentiation state of single NSC by using electrochemical and electrical techniques. Hence, the proposed technique can be used as a powerful non-destructive in situ monitoring tool for the identification of the differentiation potential of various kinds of stem cells (mesenchymal, hematopoietic, and neural stem cells). PMID:23937915

Experts' understanding of partial derivatives using the partial derivative machine

NASA Astrophysics Data System (ADS)

Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

2015-12-01

[This paper is part of the Focused Collection on Upper Division Physics Courses.] Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. In this paper, we report on an initial study of expert understanding of partial derivatives across three disciplines: physics, engineering, and mathematics. We report on the central research question of how disciplinary experts understand partial derivatives, and how their concept images of partial derivatives differ, with a focus on experimentally measured quantities. Using the partial derivative machine (PDM), we probed expert understanding of partial derivatives in an experimental context without a known functional form. In particular, we investigated which representations were cued by the experts' interactions with the PDM. Whereas the physicists and engineers were quick to use measurements to find a numeric approximation for a derivative, the mathematicians repeatedly returned to speculation as to the functional form; although they were comfortable drawing qualitative conclusions about the system from measurements, they were reluctant to approximate the derivative through measurement. On a theoretical front, we found ways in which existing frameworks for the concept of derivative could be expanded to include numerical approximation.

The Crisis in Scholarly Communication, Open Access, and Open Data Policies: The Libraries' Perspective

NASA Astrophysics Data System (ADS)

Besara, Rachel

2015-03-01

For years the cost of STEM databases have exceeded the rate of inflation. Libraries have reallocated funds for years to continue to provide support to their scientific communities, but they are reaching a point at many institutions where they are no longer able to provide access to many databases considered standard to support research. A possible or partial alleviation to this problem is the federal open access mandate. However, this shift challenges the current model of publishing and data management in the sciences. This talk will discuss these topics from the perspective of research libraries supporting physics and the STEM disciplines.

Telomere shortening in hematopoietic stem cell transplantation: a potential mechanism for late graft failure?

PubMed

Awaya, Norihiro; Baerlocher, Gabriela M; Manley, Thomas J; Sanders, Jean E; Mielcarek, Marco; Torok-Storb, Beverly; Lansdorp, Peter M

2002-01-01

Telomeres serve to maintain the structural integrity of chromosomes, yet each somatic cell division is associated with a decrease in telomere length. The cumulative decrease in telomere length can impose an upper limit for the number of cell divisions that can occur before a cell senesces. When studied in vitro with fibroblasts, this limit is referred to as the Hayflick limit and usually occurs after 40 to 80 cell doublings. In theory, a similar replicative potential in a hematopoietic stem cell could support hematopoiesis in a person for more than 100 years. However, stem cells differentiate, and the telomere length differs among chromosomes within a single cell, among cell types, and among age-matched individuals. This variation in telomere length raises the possibility that long-term hematopoiesis by transplanted stem cells could, depending on the telomere length of the engrafted stem cell and the proliferative demand to which it is subjected, reach a Hayflick limit during the life span of the patient. Although significant shortening of telomeres is reported to occur within the first year posttransplantation, as yet no evidence has indicated that this shortening is associated with marrow function. In this review, we summarize reports on telomere shortening in stem cell transplantation recipients and report 2 cases in which graft failure is associated with significant telomere shortening.

Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome.

PubMed

Holmes, Denise K; Bates, Nicola; Murray, Mary; Ladusans, E J; Morabito, Antonino; Bolton-Maggs, Paula H B; Johnston, Tracey A; Walkenshaw, Steve; Wynn, Robert F; Bellantuono, Ilaria

2006-12-01

There is an increased risk of myeloid malignancy in individuals with Down's syndrome (DS), which is associated with a mutation in exon 2 of the transcription factor GATA-1. It is recognized that there is accelerated telomere shortening in blood cells of children with DS similar to that in conditions such as Fanconi anemia and dyskeratosis congenita. The latter conditions are associated with stem cell deficiency and clonal change, including acute myeloid leukemia. In this study we address the questions 1) whether the accelerated telomere shortening is associated with progenitor/stem cell deficiency in individuals with DS, predisposing to clonal change and 2) whether the occurrence of reduced numbers of stem/progenitor cells precede the incidence of mutations in exon 2 of GATA-1. Peripheral blood from fetuses (23-35 weeks gestation) and/or bone marrow from children affected by DS and age-matched hematologically healthy controls were analyzed for telomere length, content of stem/progenitor cells, and mutations in exon 2 of GATA-1. We found that hematopoietic stem/progenitor cell deficiency and telomere shortening occurs in individuals with DS in fetal life. Moreover, the presence of a low number of progenitor cells was not associated with mutations in exon 2 of GATA-1. We propose that stem cell deficiency may be a primary predisposing event to DS leukemia development.

Comparing partial cutttng practices in central Appalachian hardwoods

Treesearch

G.W. Miller; H.C. Smith

1991-01-01

Variations of diameter-limit and perhaps single-tree selection harvesting are used to regenerate and manage central Appalachian hardwood sawtimber stands. In practice, these methods differ in terms of cut rules, control of stand structure, and cultural treatment of immature stems. Preliminary information is provided to compare the effect of two differing harvest...

Preliminary data from Arbuckle test wells, Miami, Douglas, Saline, and Labette counties, Kansas

USGS Publications Warehouse

Gogel, Tony

1981-01-01

Formation data from drill-stem tests are presented for use in calculating transmissivity, hydraulic conductivity, and hydraulic head. Complete analyses of water samples from wells at sites 2, 3, and 4, and a partial analysis at site 1, are presented to indicate water quality in the aquifers.

A (R)evaluation of Nietzsche's Anti-Democratic Pedagogy: The Overman, Perspectivism, and Self-Overcoming

ERIC Educational Resources Information Center

Jonas, Mark E.

2009-01-01

In this paper, I argue that Friedrich Nietzsche's concept of self-overcoming has been largely misinterpreted in the philosophy of education journals. The misinterpretation partially stems from a misconstruction of Nietzsche's perspectivism, and leads to a conception of self-overcoming that is inconsistent with Nietzsche's educational ideals. To…

Partial T-cell depletion improves the composite endpoint graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic stem cell transplantation.

PubMed

Simonetta, Federico; Masouridi-Levrat, Stavroula; Beauverd, Yan; Tsopra, Olga; Tirefort, Yordanka; Koutsi, Aikaterini; Stephan, Caroline; Polchlopek-Blasiak, Karolina; Pradier, Amandine; Dantin, Carole; Ansari, Marc; Roosnek, Eddy; Chalandon, Yves

2018-03-01

Graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) is a recently reported composite endpoint that allows to simultaneously estimate risk of death, relapse and GvHD after allogeneic hematopoietic stem cell transplantation (HSCT). In this retrospective study comprising 333 patients transplanted for hematologic malignancies, we compared GRFS in patients receiving partial T-cell-depleted (pTCD) grafts with patients receiving T-cell-replete grafts (No-TCD). pTCD was associated with a significantly improved GRFS. The beneficial effect of pTCD on GRFS remained highly significant in multivariable analysis taking into account clinical factors differing between patient groups. We observed no effect of pTCD on overall survival, progression-free survival, and relapse cumulative incidence, while non-relapse mortality cumulative incidence was significantly lower in patients receiving pTCD. The results of our retrospective analysis suggest that pTCD could improve GRFS in allogeneic HSCT recipients without significantly affecting OS and PFS, thus improving patients' quality of life without impairing the curative potential of allogeneic HSCT.

Protégé Perceptions of High Mentorship Quality Depend on Shared Values More than on Demographic Match

ERIC Educational Resources Information Center

Hernandez, Paul R.; Estrada, Mica; Woodcock, Anna; Schultz, P. Wesley

2017-01-01

Mentoring, particularly same-gender and same-race mentoring, is increasingly seen as a powerful method to attract and retain more women and racial minorities into science, technology, engineering, and mathematics (STEM) education and careers. This study examines elements of a mentoring dyad relationship (i.e., demographic and perceived similarity…

Perception and Bias in the Processing of Compound versus Phrasal Stress: Evidence from Event-Related Brain Potentials

ERIC Educational Resources Information Center

McCauley, Stewart M; Hestvik, Arild; Vogel, Irene

2013-01-01

Previous research using picture/word matching tasks has demonstrated a tendency to incorrectly interpret phrasally stressed strings as compounds. Using event-related potentials, we sought to determine whether this pattern stems from poor perceptual sensitivity to the compound/phrasal stress distinction, or from a post-perceptual bias in behavioral…

Matched and Mismatched Appraisals of the Effectiveness of Communication Strategies by Family Caregivers of Persons with Alzheimer's Disease

ERIC Educational Resources Information Center

Savundranayagam, Marie Y.; Orange, J. B.

2014-01-01

Background: Communication problems stemming from Alzheimer's disease (AD) often result in misunderstandings that can be linked with problem behaviours and increased caregiver stress. Moreover, these communication breakdowns also can result either from caregivers' use of ineffective communication strategies, which paradoxically are…

Effect of Sampling Schedule on Pharmacokinetic Parameter Estimates of Promethazine in Astronauts

NASA Technical Reports Server (NTRS)

Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

2005-01-01

Six astronauts on the Shuttle Transport System (STS) participated in an investigation on the pharmacokinetics of promethazine (PMZ), a medication used for the treatment of space motion sickness (SMS) during flight. Each crewmember completed the protocol once during flight and repeated thirty days after returned to Earth. Saliva samples were collected at scheduled times for 72 h after PMZ administration; more frequent samples were collected on the ground than during flight owing to schedule constraints in flight. PMZ concentrations in saliva were determined by a liquid chromatographic/mass spectrometric (LC-MS) assay and pharmacokinetic parameters (PKPs) were calculated using actual flight and ground-based data sets and using time-matched sampling schedule on ground to that during flight. Volume of distribution (V(sub c)) and clearance (Cl(sub s),) decreased during flight compared to that from time-matched ground data set; however, Cl(sub s) and V(sub c) estimates were higher for all subjects when partial ground data sets were used for analysis. Area under the curve (AUC) normalized with administered dose was similar in flight and partial ground data; however AUC was significantly lower using time-matched sampling compared with the full data set on ground. Half life (t(sub 1/2)) was longest during flight, shorter with matched-sampling schedule on ground and shortest when complete data set from ground was used. Maximum concentration (C(sub max)), time for C(sub max), (t(sub max)), parameters of drug absorption, depicted a similar trend with lowest and longest respectively, during flight, lower with time-matched ground data and highest and shortest with full ground data.

Effect of sampling schedule on pharmacokinetic parameter estimates of promethazine in astronauts

NASA Astrophysics Data System (ADS)

Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

2005-08-01

Six astronauts on the Shuttle Transport System (STS) participated in an investigation on the pharmacokinetics of promethazine (PMZ), a medication used for the treatment of space motion sickness (SMS) during flight. Each crewmember completed the protocol once during flight and repeated thirty days after returned to Earth. Saliva samples were collected at scheduled times for 72 h after PMZ administration; more frequent samples were collected on the ground than during flight owing to schedule constraints in flight. PMZ concentrations in saliva were determined by a liquid chromatographic/mass spectrometric (LC-MS) assay and pharmacokinetic parameters (PKPs) were calculated using actual flight and ground-based data sets and using time-matched sampling schedule on ground to that during flight. Volume of distribution (Vc) and clearance (Cls) decreased during flight compared to that from time-matched ground data set; however, ClS and Vc estimates were higher for all subjects when partial ground data sets were used for analysis. Area under the curve (AUC) normalized with administered dose was similar in flight and partial ground data; however AUC was significantly lower using time-matched sampling compared with the full data set on ground. Half life (t1/2) was longest during flight, shorter with matched-sampling schedule on ground and shortest when complete data set from ground was used. Maximum concentration (Cmax), time for Cmax (tmax), parameters of drug absorption, depicted a similar trend with lowest and longest respectively, during flight, lower with time- matched ground data and highest and shortest with full ground data.

Coherent detection of frequency-hopped quadrature modulations in the presence of jamming. II - QPR Class I modulation. [Quadrature Partial Response

NASA Technical Reports Server (NTRS)

Simon, M. K.

1981-01-01

This paper considers the performance of quadrature partial response (QPR) in the presence of jamming. Although a QPR system employs a single sample detector in its receiver, while quadrature amplitude shift keying (or quadrature phase shift keying) requires a matched-filter type of receiver, it is shown that the coherent detection performances of the two in the presence of the intentional jammer have definite similarities.

A rotation-translation invariant molecular descriptor of partial charges and its use in ligand-based virtual screening

PubMed Central

2014-01-01

Background Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Molecular similarity has been measured by a variety of methods including molecular descriptor based similarity, common molecular fragments, graph matching and 3D methods such as shape matching. Similarity measures are widespread in practice and have proven to be useful in drug discovery. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule. Results A new molecular descriptor based on partial charges is proposed. It uses the autocorrelation function and linear binning to encode all atoms of a molecule into two rotation-translation invariant vectors. Combined with a scoring function, the descriptor allows to rank-order a database of compounds versus a query molecule. The proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and released in open source. Extensive retrospective ligand-based virtual screening experiments were performed and other methods were compared with in order to validate the method and associated protocol. Conclusions While it is a simple method, it performed remarkably well in experiments. At an average speed of 1649 molecules per second, it reached an average median area under the curve of 0.81 on 40 different targets; hence validating the proposed protocol and implementation. PMID:24887178

Simple Signaling Molecules for Inductive Bone Regenerative Engineering

PubMed Central

Nelson, Stephen J.; Deng, Meng; Sethuraman, Swaminathan; Doty, Stephen B.; Lo, Kevin W. H.; Khan, Yusuf M.; Laurencin, Cato T.

2014-01-01

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors. PMID:25019622

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.

Wnt/β-catenin and LIF-Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal.

PubMed

Ye, Shoudong; Zhang, Dongming; Cheng, Fei; Wilson, Daniel; Mackay, Jeffrey; He, Kan; Ban, Qian; Lv, Feng; Huang, Saifei; Liu, Dahai; Ying, Qi-Long

2016-01-15

Activation of leukemia inhibitor factor (LIF)-Stat3 or Wnt/β-catenin signaling promotes mouse embryonic stem cell (mESC) self-renewal. A myriad of downstream targets have been identified in the individual signal pathways, but their common targets remain largely elusive. In this study, we found that the LIF-Stat3 and Wnt/β-catenin signaling pathways converge on Sp5 to promote mESC self-renewal. Forced Sp5 expression can reproduce partial effects of Wnt/β-catenin signaling but mimics most features of LIF-Stat3 signaling to maintain undifferentiated mESCs. Moreover, Sp5 is able to convert mouse epiblast stem cells into a naïve pluripotent state. Thus, Sp5 is an important component of the regulatory network governing mESC naïve pluripotency. © 2016. Published by The Company of Biologists Ltd.

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Sketch Matching on Topology Product Graph.

PubMed

Liang, Shuang; Luo, Jun; Liu, Wenyin; Wei, Yichen

2015-08-01

Sketch matching is the fundamental problem in sketch based interfaces. After years of study, it remains challenging when there exists large irregularity and variations in the hand drawn sketch shapes. While most existing works exploit topology relations and graph representations for this problem, they are usually limited by the coarse topology exploration and heuristic (thus suboptimal) similarity metrics between graphs. We present a new sketch matching method with two novel contributions. We introduce a comprehensive definition of topology relations, which results in a rich and informative graph representation of sketches. For graph matching, we propose topology product graph that retains the full correspondence for matching two graphs. Based on it, we derive an intuitive sketch similarity metric whose exact solution is easy to compute. In addition, the graph representation and new metric naturally support partial matching, an important practical problem that received less attention in the literature. Extensive experimental results on a real challenging dataset and the superior performance of our method show that it outperforms the state-of-the-art.

Specific problems in visual cognition of dyslexic readers: Face discrimination deficits predict dyslexia over and above discrimination of scrambled faces and novel objects.

PubMed

Sigurdardottir, Heida Maria; Fridriksdottir, Liv Elisabet; Gudjonsdottir, Sigridur; Kristjánsson, Árni

2018-06-01

Evidence of interdependencies of face and word processing mechanisms suggest possible links between reading problems and abnormal face processing. In two experiments we assessed such high-level visual deficits in people with a history of reading problems. Experiment 1 showed that people who were worse at face matching had greater reading problems. In experiment 2, matched dyslexic and typical readers were tested, and difficulties with face matching were consistently found to predict dyslexia over and above both novel-object matching as well as matching noise patterns that shared low-level visual properties with faces. Furthermore, ADHD measures could not account for face matching problems. We speculate that reading difficulties in dyslexia are partially caused by specific deficits in high-level visual processing, in particular for visual object categories such as faces and words with which people have extensive experience. Copyright © 2018 Elsevier B.V. All rights reserved.

High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: how can they be used to improve unrelated donor searches?

PubMed

Pingel, Julia; Solloch, Ute V; Hofmann, Jan A; Lange, Vinzenz; Ehninger, Gerhard; Schmidt, Alexander H

2013-03-01

In hematopoietic stem cell transplantation, human leukocyte antigens (HLA), usually HLA loci A, B, C, DRB1 and DQB1, are required to check histocompatibility between a potential donor and the recipient suffering from a malignant or non-malignant blood disease. As databases of potential unrelated donors are very heterogeneous with respect to typing resolution and number of typed loci, donor registries make use of haplotype frequency-based algorithms to provide matching probabilities for each potentially matching recipient/donor pair. However, it is well known that HLA allele and haplotype frequencies differ significantly between populations. We estimated high-resolution HLA-A, -B, -C, -DRB1 haplotype and allele frequencies of donors within DKMS German Bone Marrow Donor Center with parentage from 17 different countries: Turkey, Poland, Italy, Russian Federation, Croatia, Greece, Austria, Kazakhstan, France, The Netherlands, Republic of China, Romania, Portugal, USA, Spain, United Kingdom and Bosnia and Herzegovina. 5-locus haplotypes including HLA-DQB1 are presented for Turkey, Poland, Italy and Russian Federation. We calculated linkage disequilibria for each sample. Genetic distances between included countries could be shown to reflect geography. We further demonstrate how genetic differences between populations are reflected in matching probabilities of recipient/donor pairs and how they influence the search for unrelated donors as well as strategic donor center typings. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials.

PubMed

Nakane, Takahiko; Nakamae, Hirohisa; Yamaguchi, Takuhiro; Kurosawa, Saiko; Okamura, Atsuo; Hidaka, Michihiro; Fuji, Shigeo; Kohno, Akio; Saito, Takeshi; Aoyama, Yasutaka; Hatanaka, Kazuo; Katayama, Yoshio; Yakushijin, Kimikazu; Matsui, Toshimitsu; Yamamori, Motohiro; Takami, Akiyoshi; Hino, Masayuki; Fukuda, Takahiro

2017-04-01

To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7-8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II-IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8-62.5) and 25.8% (90% CI 13.9-39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation.

PubMed

Yu, Junli; Venstrom, Jeffrey M; Liu, Xiao-Rong; Pring, James; Hasan, Reenat S; O'Reilly, Richard J; Hsu, Katharine C

2009-04-16

Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-gamma and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell-derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis.

PubMed

Gertz, Morie A; Lacy, Martha Q; Dispenzieri, Angela; Buadi, Francis K; Dingli, David; Hayman, Suzanne R; Kumar, Shaji K; Leung, Nelson; Lust, John; Rajkumar, S Vincent; Russell, Stephen J; Suman, Vera J; Le-Rademacher, Jennifer G; Hogan, William J

2016-07-15

Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival. Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis. Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01). Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. © 2016 American Cancer Society.

Characterization of LiBC by phase-contrast scanning transmission electron microscopy.

PubMed

Krumeich, Frank; Wörle, Michael; Reibisch, Philipp; Nesper, Reinhard

2014-08-01

LiBC was used as a model compound for probing the applicability of phase-contrast (PC) imaging in an aberration-corrected scanning transmission electron microscope (STEM) to visualize lithium distributions. In the LiBC structure, boron and carbon are arranged to hetero graphite layers between which lithium is incorporated. The crystal structure is reflected in the PC-STEM images recorded perpendicular to the layers. The experimental images and their defocus dependence match with multi-slice simulations calculated utilizing the reciprocity principle. The observation that a part of the Li positions is not occupied is likely an effect of the intense electron beam triggering Li displacement. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

PubMed

Kook, H; Goldman, F; Padley, D; Giller, R; Rumelhart, S; Holida, M; Lee, N; Peters, C; Comito, M; Huling, D; Trigg, M

1996-08-01

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated With Cyclophosphamide.

PubMed

Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J

2018-06-15

Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Biogeographical patterns of biomass allocation in leaves, stems, and roots in China's forests.

PubMed

Zhang, Hao; Wang, Kelin; Xu, Xianli; Song, Tongqing; Xu, Yanfang; Zeng, Fuping

2015-11-03

To test whether there are general patterns in biomass partitioning in relation to environmental variation when stand biomass is considered, we investigated biomass allocation in leaves, stems, and roots in China's forests using both the national forest inventory data (2004-2008) and our field measurements (2011-2012). Distribution patterns of leaf, stem, and root biomass showed significantly different trends according to latitude, longitude, and altitude, and were positively and significantly correlated with stand age and mean annual precipitation. Trade-offs among leaves, stems, and roots varied with forest type and origin and were mainly explained by stand biomass. Based on the constraints of stand biomass, biomass allocation was also influenced by forest type, origin, stand age, stand density, mean annual temperature, precipitation, and maximum temperature in the growing season. Therefore, after stand biomass was accounted for, the residual variation in biomass allocation could be partially explained by stand characteristics and environmental factors, which may aid in quantifying carbon cycling in forest ecosystems and assessing the impacts of climate change on forest carbon dynamics in China.

Maceration with stems contact fermentation: effect on proanthocyanidins compounds and color in Primitivo red wines.

PubMed

Suriano, Serafino; Alba, Vittorio; Tarricone, Luigi; Di Gennaro, Domenico

2015-06-15

Three Primitivo (Vitis vinifera, cv.) red wines were microvinified by means of different winemaking technologies: no stem-contact fermentation destemming 100% of grapes (D100); stem-contact fermentation destemming 75%, 50% of grapes (D75-D50) respectively. The objectives of this work were to improve proanthocyanidins content in wine, to monitor the relationships between anthocyanins/tannins and to detect the effects on the polymerization state of polyphenols after 12 months storage of wines. D100 showed higher anthocyanins content but lower color intensity and phenolic compounds content with respect to the theses D75 and D50, the last two showing lower anthocyanins content due their partial adsorption by grape stems during the fermentation. D75 gave the best results in terms of anthocyanins/color intensity balance and showed a better wine tannin component with respect to D50. Moreover after 12 months storage D50 reached a more advanced and stable polymerization state of colored pigments than the other wines. Copyright © 2015 Elsevier Ltd. All rights reserved.

CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells.

PubMed

Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

2016-01-01

Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, chemo-resistance property and in vivo tumor formation abilities were detected. A549 CD24- cells formed smaller colonies, slower proliferated in comparison to A549 CD24+ cells. Besides, A549 CD24- exhibited stronger resistance to chemotherapy drug. However, A549 CD24- didn't exert any stronger tumor formation ability in vivo, which is the gold standard of CSCs. These results showed that CD24- A549 cells showed some properties of CSCs but not actually CSCs. This study provides evidence that CD24 cannot be considered as lung CSCs marker.

Fate of Lu(III) sorbed on 2-line ferrihydrite at pH 5.7 and aged for 12 years at room temperature. II: insights from STEM-EDXS and DFT calculations.

PubMed

Yokosawa, Tadahiro; Prestat, Eric; Polly, Robert; Bouby, Muriel; Dardenne, Kathy; Finck, Nicolas; Haigh, Sarah J; Denecke, Melissa A; Geckeis, Horst

2018-04-18

Transformation products of two-line ferrihydrite associated with Lu(III) were studied after 12 years of aging using aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM), high-efficiency energy-dispersive X-ray spectroscopy (EDXS), and density functional theory (DFT). The transformation products consisted of hematite nanoparticles with overgrown goethite needles. High-efficiency STEM-EDXS revealed that Lu is only associated with goethite needles, and atomic-resolution HAADF-STEM reveals structural incorporation of Lu within goethite, partially replacing structural Fe sites. This finding corroborates those recently obtained by AsFlFFF and EXAFS spectroscopy on the same sample (Finck et al. 2018). DFT calculations indicate that Lu incorporation within goethite or hematite are almost equally likely, suggesting that experimental parameters such as temperature and reaction time which affect reaction kinetics, play important roles in determining the Lu uptake. It seems likely that these results may be transferable to predict the behavior of chemically homologous trivalent actinides.

Biogeographical patterns of biomass allocation in leaves, stems, and roots in China’s forests

PubMed Central

Zhang, Hao; Wang, Kelin; Xu, Xianli; Song, Tongqing; Xu, Yanfang; Zeng, Fuping

2015-01-01

To test whether there are general patterns in biomass partitioning in relation to environmental variation when stand biomass is considered, we investigated biomass allocation in leaves, stems, and roots in China’s forests using both the national forest inventory data (2004–2008) and our field measurements (2011–2012). Distribution patterns of leaf, stem, and root biomass showed significantly different trends according to latitude, longitude, and altitude, and were positively and significantly correlated with stand age and mean annual precipitation. Trade-offs among leaves, stems, and roots varied with forest type and origin and were mainly explained by stand biomass. Based on the constraints of stand biomass, biomass allocation was also influenced by forest type, origin, stand age, stand density, mean annual temperature, precipitation, and maximum temperature in the growing season. Therefore, after stand biomass was accounted for, the residual variation in biomass allocation could be partially explained by stand characteristics and environmental factors, which may aid in quantifying carbon cycling in forest ecosystems and assessing the impacts of climate change on forest carbon dynamics in China. PMID:26525117

Xylem vulnerability to cavitation can be accurately characterised in species with long vessels using a centrifuge method.

PubMed

Tobin, M F; Pratt, R B; Jacobsen, A L; De Guzman, M E

2013-05-01

Vulnerability to cavitation curves describe the decrease in xylem hydraulic conductivity as xylem pressure declines. Several techniques for constructing vulnerability curves use centrifugal force to induce negative xylem pressure in stem or root segments. Centrifuge vulnerability curves constructed for long-vesselled species have been hypothesised to overestimate xylem vulnerability to cavitation due to increased vulnerability of vessels cut open at stem ends that extend to the middle or entirely through segments. We tested two key predictions of this hypothesis: (i) centrifugation induces greater embolism than dehydration in long-vesselled species, and (ii) the proportion of open vessels changes centrifuge vulnerability curves. Centrifuge and dehydration vulnerability curves were compared for a long- and short-vesselled species. The effect of open vessels was tested in four species by comparing centrifuge vulnerability curves for stems of two lengths. Centrifuge and dehydration vulnerability curves agreed well for the long- and short-vesselled species. Centrifuge vulnerability curves constructed using two stem lengths were similar. Also, the distribution of embolism along the length of centrifuged stems matched the theoretical pressure profile induced by centrifugation. We conclude that vulnerability to cavitation can be accurately characterised with vulnerability curves constructed using a centrifuge technique, even in long-vesselled species. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Dislocation imaging for orthopyroxene using an atom-resolved scanning transmission electron microscopy.

PubMed

Kumamoto, Akihito; Kogure, Toshihiro; Raimbourg, Hugues; Ikuhara, Yuichi

2014-11-01

Dislocations, one-dimensional lattice defects, appear as a microscopic phenomenon while they are formed in silicate minerals by macroscopic dynamics of the earth crust such as shear stress. To understand ductile deformation mechanisms of silicates, atomic structures of the dislocations have been examined using transmission electron microscopy (TEM). Among them, it has been proposed that {100}<001> primary slip system of orthopyroxene (Opx) is dissociated into partial dislocations, and a stacking fault with the clinopyroxene (Cpx) structure is formed between the dislocations. This model, however, has not been determined completely due to the complex structures of silicates. Scanning transmission electron microscopy (STEM) has a potential to determine the structure of dislocations with single-atomic column sensitivity, particularly by using high-angle annular dark field (HAADF) and annular bright field (ABF) imaging with a probing aberration corrector.[1] Furthermore, successive analyses from light microscopy to atom-resolved STEM have been achieved by focused ion beam (FIB) sampling techniques.[2] In this study, we examined dislocation arrays at a low-angle grain boundary of ∼1° rotation about the b-axis in natural deformed Opx using a simultaneous acquisition of HAADF/ABF (JEM-ARM200F, JEOL) equipped with 100 mm2 silicon drift detector (SDD) for energy dispersive X-ray spectroscopy (EDS). Figure 1 shows averaged STEM images viewed along the b- axis of Opx extracted from repeating units. HAADF provides the cation-site arrangement, and ABF distinguishes the difference of slightly rotated SiO4 tetrahedron around the a- axis. This is useful to distinguish the change of stacking sequence between the partial dislocations. Two types of stacking faults with Cpx and protopyroxene (Ppx) structures were identified between three partial dislocations. Furthermore, Ca accumulation in M2 (Fe) site around the stacking faults was detected by STEM-EDS. Interestingly, Ca is distributed not only in these stacking faults but also Opx matrix around the faults. jmicro;63/suppl_1/i17/DFU063F1F1DFU063F1Fig. 1. (a) HAADF and (b) ABF of Opx view of [010] direction with inset simulation images and models of its unit cell (a = 0.52, c = 1.83 nm). © The Author 2014. 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.

Emodin Suppresses Maintenance of Stemness by Augmenting Proteosomal Degradation of Epidermal Growth Factor Receptor/Epidermal Growth Factor Receptor Variant III in Glioma Stem Cells

PubMed Central

Kim, Jeongyub; Lee, Jong-Seon; Jung, Jieun; Lim, Inhye; Lee, Ji-Yun

2015-01-01

There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs. PMID:25229646

High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem.

PubMed

Licursi, Maria; Alberto, Christian O; Dias, Alex; Hirasawa, Kensuke; Hirasawa, Michiru

2016-11-01

High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated. Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1β, IL-6, TNF-α, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS). HFD increased pontine TNF-α mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability. HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS. © 2016 The Obesity Society.

Gravitropism in Higher Plant Shoots 1

PubMed Central

Sliwinski, Julianne E.; Salisbury, Frank B.

1984-01-01

Cross and longitudinal sections were prepared for light microscopy from vertical control plants (Xanthium strumarium L. Chicago strain), free-bending horizontal stems, plants restrained 48 hours in a horizontal position, and plants restrained 48 hours and then released, bending immediately about 130°. Top cells of free-bending stems shrink or elongate little; bottom cells continue to elongate. In restrained stems, bottom cells elongate some and increase in diameter; top cells elongate about as much but decrease in diameter. Upon release, bottom cells elongate more and decrease in diameter, while top cells shorten and increase in diameter, accounting for the bend. During restraint, bottom cells take up water while tissue pressures increase; top cells fail to take up water although tissue pressures are decreasing. Settling of amyloplasts was observed in cells of the starch sheath. Removal of different amounts of stem (Xanthium; Lycopersicon esculentum Miller, cv Bonny Best; Ricinus communis L. cv Yolo Wonder) showed that perception of gravity occurs in the bending (elongation) zone, although bending of fourth and fifth internodes from the top was less than in uncut controls. Uniform application of 1% indoleacetic acid in lanolin to cut stem surfaces partially restored bending. Reversing the gradient in tension/compression in horizontal stems (top under compression, bottom under tension) did not affect gravitropic bending. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:16663939

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

Reversing glioma malignancy: a new look at the role of antidepressant drugs as adjuvant therapy for glioblastoma multiforme.

PubMed

Bielecka-Wajdman, Anna M; Lesiak, Marta; Ludyga, Tomasz; Sieroń, Aleksander; Obuchowicz, Ewa

2017-06-01

The role of glioma stem cells (GSCs) in cancer progression is currently debated; however, it is hypothesised that this subpopulation is partially responsible for therapeutic resistance observed in glioblastoma multiforme (GBM). Recent studies have shown that the current treatments not only fail to eliminate the GSC population but even promote GSCs through reprogramming of glioma non-stem cells to stem cells. Since the standard GBM treatment often requires supplementation with adjuvant drugs such as antidepressants, their role in the regulation of the heterogeneous nature of GSCs needs evaluation. We examined the effects of imipramine, amitriptyline, fluoxetine, mirtazapine, agomelatine, escitalopram, and temozolomide on the phenotypic signature (CD44, Ki67, Nestin, Sox1, and Sox2 expression) of GSCs isolated from a human T98G cell line. These drugs were examined in several models of hypoxia (1% oxygen, 2.5% oxygen, and a hypoxia-reoxygenation model) as compared to the standard laboratory conditions (20% oxygen). We report that antidepressant drugs, particularly imipramine and amitriptyline, modulate plasticity, silence the GSC profile, and partially reverse the malignant phenotype of GBM. Moreover, we observed that, in contrast to temozolomide, these tricyclic antidepressants stimulated viability and mitochondrial activity in normal human astrocytes. The ability of phenotype switching from GSC to non-GSC as stimulated by antidepressants (primarily imipramine and amitriptyline) sheds new light on the heterogeneous nature of GSC, as well as the role of antidepressants in adjuvant GBM therapy.

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

PubMed

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice.

PubMed

Sironi, Francesca; Vallarola, Antonio; Violatto, Martina Bruna; Talamini, Laura; Freschi, Mattia; De Gioia, Roberta; Capelli, Chiara; Agostini, Azzurra; Moscatelli, Davide; Tortarolo, Massimo; Bigini, Paolo; Introna, Martino; Bendotti, Caterina

2017-12-01

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression. Copyright © 2017. Published by Elsevier B.V.

When Does Reward Maximization Lead to Matching Law?

PubMed Central

Sakai, Yutaka; Fukai, Tomoki

2008-01-01

What kind of strategies subjects follow in various behavioral circumstances has been a central issue in decision making. In particular, which behavioral strategy, maximizing or matching, is more fundamental to animal's decision behavior has been a matter of debate. Here, we prove that any algorithm to achieve the stationary condition for maximizing the average reward should lead to matching when it ignores the dependence of the expected outcome on subject's past choices. We may term this strategy of partial reward maximization “matching strategy”. Then, this strategy is applied to the case where the subject's decision system updates the information for making a decision. Such information includes subject's past actions or sensory stimuli, and the internal storage of this information is often called “state variables”. We demonstrate that the matching strategy provides an easy way to maximize reward when combined with the exploration of the state variables that correctly represent the crucial information for reward maximization. Our results reveal for the first time how a strategy to achieve matching behavior is beneficial to reward maximization, achieving a novel insight into the relationship between maximizing and matching. PMID:19030101

Single-frequency oscillation of thin-disk lasers due to phase-matched pumping.

PubMed

Vorholt, Christian; Wittrock, Ulrich

2017-09-04

We present a novel pump concept that should lead to single-frequency operation of thin-disk lasers without the need for etalons or other spectral filters. The single-frequency operation is due to matching the standing wave pattern of partially coherent pump light to the standing wave pattern of the laser light inside the disk. The output power and the optical efficiency of our novel pump concept are compared with conventional pumping. The feasibility of our pump concept was shown in previous experiments.

The SAPHIRE server: a new algorithm and implementation.

PubMed Central

Hersh, W.; Leone, T. J.

1995-01-01

SAPHIRE is an experimental information retrieval system implemented to test new approaches to automated indexing and retrieval of medical documents. Due to limitations in its original concept-matching algorithm, a modified algorithm has been implemented which allows greater flexibility in partial matching and different word order within concepts. With the concomitant growth in client-server applications and the Internet in general, the new algorithm has been implemented as a server that can be accessed via other applications on the Internet. PMID:8563413

Preparation of Underrepresented Males for Scientific Careers: A Study of the Dr. John H. Hopps Jr. Defense Research Scholars Program at Morehouse College.

PubMed

Thompson, Rahmelle C; Monroe-White, Thema; Xavier, Jeffrey; Howell, Courtney; Moore, Myisha Roberson; Haynes, J K

Equal representation within higher education science, technology, engineering, and mathematics (STEM) fields and the STEM workforce in the United States across demographically diverse populations is a long-standing challenge. This study uses two-to-one nearest-neighbor matched-comparison group design to examine academic achievement, pursuit of graduate science degree, and classification of graduate institution attended by students participating in the Hopps Scholars Program (Hopps) at Morehouse College. Hopps is a highly structured enrichment program aimed at increasing participation of black males in STEM fields. Morehouse institutional records, Hopps Program records, and National Student Clearinghouse data were used to examine differences between Hopps and non-Hopps STEM graduates of Morehouse. Two-way sample t tests and chi-square tests revealed significant differences in academic achievement, likelihood of STEM degree pursuit, and the classification of graduate institutions attended by Hopps versus non-Hopps students. Hopps Scholars were significantly more likely than non-Hopps STEM graduates both to pursue STEM doctoral degrees and to attend doctoral-granting institutions with higher research activity. The Hopps Program's approach to training black male students for scientific careers is a model of success for other programs committed to increasing the number of black males pursuing advanced degrees in STEM. © 2016 R. C. Thompson et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Hematopoietic Stem Cell Transplant in Adolescent and Young Adults With Fanconi Anemia Is Feasible With Acceptable Toxicity, With Those Surviving 100 Days Posttransplant Having Excellent Outcomes.

PubMed

Alhuraiji, Ahmad; Alzahrani, Hazza; Al Mohareb, Fahad; Chaudhri, Naeem; Alsharif, Fahad; Mohamed, Said; Rasheed, Walid; Aldawsari, Ghuzayel; Ahmed, Syed Osman; Aljurf, Mahmoud

2016-12-01

Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.

[Outcome of haploidentical hematopoietic stem cell transplantation for non-Hodgkin lymphoma].

PubMed

Xu, T; Chen, J; Jin, Z M; Miao, M; Fu, C C; Qiu, H Y; Tang, X W; Han, Y; Sun, A N; Wu, D P

2016-08-14

To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo- HSCT) for refractory, relapsed or highly aggressive non- Hodgkin lymphoma (NHL) patients. A total of 26 patients with refractory, relapsed or highly aggressive NHL who received Haplo- HSCT from Jan. 2004 to Mar. 2015 were analyzed retrospectively. Of them, 4 patients had diffuse large B-cell lymphoma (DLBCL), 1 had follicular lymphoma, 5 had B-lymphoblastic lymphoma/leukemia, 9 had T- lymphoblastic lymphoma/leukemia, 1 patient anaplastic large cell lymphoma (ALK-negative), 5 had peripheral T-cell lymphoma (NOS), and 1 had NK/T-cell lymphoma. At the time of initial diagnosis, 6 patients had Ann Arbor stage Ⅲ disease, 20 patients showed stage Ⅳ. At the time of Haplo- HSCT, 7 patients were in the first complete remission (CR1), 4 in the second complete remission (CR2), 7 in partial remission, 1 in stable disease, 7 in progressive disease, and 19 of 26 patients were refractory or relapsed. The neutrophil and platelet counts recovered at 12 (11-17) d and 14 (11-31) d after Haplo- HSCT, respectively. All patients achieved full donor chimerism at 30d after Haplo- HSCT. With a median follow- up of 14 (4- 136) months, 20 cases (76.92%) survived, 15 (57.69%) survived without lymphoma, and 7 (26.92%) relapsed. Conditioning regimen related adverse reactions were all disappeared after treatment. The estimated 2-year recurrence rate after Haplo-HSCT was 42.20%. The estimated 2-year overall survival (OS) and disease-free survival (DFS) rate was 71.60% and 48.90%, respectively. Patients in CR before Haplo- HSCT experienced better 2- year OS (100.0% vs 52.4%, P=0.023) and 2- year DFS (88.9% vs 27.0%, P=0.013). Haplo- HSCT may effective and safe for those relapsed, refractory or highly aggressive NHL patients who did not have matched donor nor suitable for autologous HSCT.

Use of Mutant-Assisted Gene Identification and Characterization (MAGIC) to identify novel genetic loci that modify the maize hypersensitive response

USDA-ARS?s Scientific Manuscript database

The partially-dominant, autoactive maize disease resistance gene Rp1-D21 causes hypersensitive response (HR) lesions to form spontaneously on the leaves and stem in the absence of pathogen recognition. The maize nested association mapping (NAM) population consists of 25 200-line subpopulations each...

A review of the regeneration dynamics of North American boreal forest tree species

Treesearch

D. F. Greene; John C. Zasada; L. Sirois; D. Kneeshaw; H. Morin; I. Charron; M. J. Simard

1999-01-01

In this review, we focus on the biotic parameters that are crucial to an understanding of the recruitment dynamics of North American boreal tree species following natural (fire, budworm infestation, windthrow) or human-induced (clearcut, partial cut) disturbances. The parameters we emphasize are (i) the production of seeds and asexual stems (both of...

Research Motives of Faculty in Academic STEM: Measurement Invariance of the Research Motivation Scale

ERIC Educational Resources Information Center

Deemer, Eric D.; Mahoney, Kevin T.; Ball, Jacqueline Hebert

2012-01-01

The authors examined the psychometric properties of the Research Motivation Scale (RMS) in a sample of faculty members (N = 337) in university science departments. It was hypothesized that the RMS would evidence partial measurement invariance across tenure status and noninvariance across gender, given the different sociocultural factors (e.g.,…

Evidence of Mobilization of Pluripotent Stem Cells into Peripheral Blood of Patients with Myocardial Ischemia

PubMed Central

Abdel-Latif, Ahmed; Zuba-Surma, Ewa K.; Ziada, Khaled M.; Kucia, Magdalena; Cohen, Donald A.; Kaplan, Alan M.; Zant, Gary Van; Selim, Samy; Smyth, Susan S.; Ratajczak, Mariusz Z.

2010-01-01

Objective The ischemic myocardium releases multiple chemotactic factors responsible for the mobilization and recruitment of bone marrow-derived cells to injured myocardium. However, the mobilization of primitive pluripotent stem cells (PSCs) enriched in Very Small Embryonic-Like stem cells (VSELs) in various cardiac ischemic scenarios is not well understood. Methods Fifty four ischemic heart disease patients, including subjects with stable angina, non-ST elevation (NSTME) myocardial infarction (MI) and ST elevation myocardial infarction (STEMI), and twelve matched controls were enrolled. The absolute numbers of circulating stem/primitive cells in samples of peripheral blood (PB) were quantitated by Image Stream Analysis and conventional flow cytometry. Gene expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4), and endothelial (vWF) markers was analyzed by real-time PCR. Results The absolute numbers of PSCs, stem cell populations enriched in VSELs and hematopoietic stem cells (HSCs) present in PB were significantly higher in STEMI patients at presentation and declined over time. There was a corresponding increase in pluripotent, cardiac and endothelial gene expression in unfractionated PB cells and sorted PB-derived primitive CD34+ cells. The absolute numbers of circulating VSELs and HSCs in STEMI correlated negatively with patients' age. Conclusions Myocardial ischemia mobilizes primitive PSCs including pluripotent VSELs into the circulation. The peak of mobilization occurs within 12 hours in patients presenting with STEMI, which may represent a therapeutic window for future clinical applications. Reduced stem cell mobilization with advancing age could explain, in part, the observation that age is associated with poor prognosis in patients with MI. PMID:20800644

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.

A Research Preparatory Program for First-Year College Students: Student Selection and Preparation Lead to Persistence in Research

ERIC Educational Resources Information Center

Baiduc, Rachael R.; Drane, Denise; Beitel, Greg J.; Flores, Luke C.

2017-01-01

Undergraduate research experiences may increase persistence in STEM majors. We describe a research program that targets first-year students selected for their curiosity and attitudes towards science. We explain the implementation of the program over 3 years and present evaluation data using a group of matched controls. Participants and controls…

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

PubMed

Samuel, G N; Kerridge, I H; Vowels, M; Trickett, A; Chapman, J; Dobbins, T

2007-10-01

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR). It also examines the ethnic diversity of those patients who, after requesting a haematopoietic stem cell transplantation in the 2-year period between 2003 and 2005, managed to find a suitably matched bone marrow or UCB donor. We show that the ethnic mix of donors to the SCBB has remained generally broad in source, is comparative to the Australian population, and is more diverse than the ABMDR. This, however, may still not be sufficient to substantially increase the likelihood of finding a donor for some ethnic minority groups.

Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia

PubMed Central

Gribben, John G.; Zahrieh, David; Stephans, Katherine; Bartlett-Pandite, Lini; Alyea, Edwin P.; Fisher, David C.; Freedman, Arnold S.; Mauch, Peter; Schlossman, Robert; Sequist, Lecia V.; Soiffer, Robert J.; Marshall, Blossom; Neuberg, Donna; Ritz, Jerome; Nadler, Lee M.

2005-01-01

We report here on the long-term follow-up on 162 patients with high-risk chronic lymphocytic leukemia (CLL) who have undergone hematopoietic stem cell transplantation (SCT) at a single center from 1989 to 1999. Twenty-five patients with human leukocyte antigen (HLA)-matched sibling donors underwent T-cell-depleted allogeneic SCT, and 137 patients without HLA-matched sibling donors underwent autologous SCT. The 100-day mortality was 4% for both groups, but later morbidity and mortality were negatively affected on outcome. Progression-free survival was significantly longer following autologous than allogeneic SCT, but there was no difference in overall survival and no difference in the cumulative incidence of disease recurrence or deaths without recurrence between the 2 groups. At a median follow-up of 6.5 years there is no evidence of a plateau of progression-free survival. The majority of patients treated with donor lymphocyte infusions after relapse responded, demonstrating a significant graft-versus-leukemia effect in CLL. From these findings we have altered our approach for patients with high-risk CLL and are currently exploring the role of related and unrelated allogeneic SCT following reduced-intensity conditioning regimens. PMID:16131571

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

Biosynthesis of ribosomal RNA in nucleoli regulates pluripotency and differentiation ability of pluripotent stem cells.

PubMed

Watanabe-Susaki, Kanako; Takada, Hitomi; Enomoto, Kei; Miwata, Kyoko; Ishimine, Hisako; Intoh, Atsushi; Ohtaka, Manami; Nakanishi, Mahito; Sugino, Hiromu; Asashima, Makoto; Kurisaki, Akira

2014-12-01

Pluripotent stem cells have been shown to have unique nuclear properties, for example, hyperdynamic chromatin and large, condensed nucleoli. However, the contribution of the latter unique nucleolar character to pluripotency has not been well understood. Here, we show that fibrillarin (FBL), a critical methyltransferase for ribosomal RNA (rRNA) processing in nucleoli, is one of the proteins highly expressed in pluripotent embryonic stem (ES) cells. Stable expression of FBL in ES cells prolonged the pluripotent state of mouse ES cells cultured in the absence of leukemia inhibitory factor (LIF). Analyses using deletion mutants and a point mutant revealed that the methyltransferase activity of FBL regulates stem cell pluripotency. Knockdown of this gene led to significant delays in rRNA processing, growth inhibition, and apoptosis in mouse ES cells. Interestingly, both partial knockdown of FBL and treatment with actinomycin D, an inhibitor of rRNA synthesis, induced the expression of differentiation markers in the presence of LIF and promoted stem cell differentiation into neuronal lineages. Moreover, we identified p53 signaling as the regulatory pathway for pluripotency and differentiation of ES cells. These results suggest that proper activity of rRNA production in nucleoli is a novel factor for the regulation of pluripotency and differentiation ability of ES cells. © 2014 AlphaMed Press.

Blue light-induced phototropism of inflorescence stems and petioles is mediated by phototropin family members phot1 and phot2.

PubMed

Kagawa, Takatoshi; Kimura, Mitsuhiro; Wada, Masamitsu

2009-10-01

Phototropin family photoreceptors, phot1 and phot2, in Arabidopsis thaliana control the blue light (BL)-mediated phototropic responses of the hypocotyl, chloroplast relocation movement and stomatal opening. Phototropic responses in dark-grown tissues have been well studied but those in de-etiolated green plants are not well understood. Here, we analyzed phototropic responses of inflorescence stems and petioles of wild-type and phototropin mutant plants of A. thaliana. Similar to the results obtained from dark-grown seedlings, inflorescence stems and petioles in wild-type and phot2 mutant plants showed phototropic bending towards low fluence BL, while in phot1 mutant plants, a high fluence rate of BL was required. phot1 phot2 double mutant plants did not show any phototropic responses even under very high fluence rates of BL. We further studied the photoreceptive sites for phototropic responses of stems and petioles by partial tissue irradiation. The whole part of the inflorescence stem is sensitive to BL and shows phototropism, but in the petiole only the irradiated abaxial side is sensitive. Similar to dark-grown etiolated seedlings, phot1 plays a major role in phototropic responses under weak light, but phot2 functions under high fluence rate conditions in green plants.

Mechanism of gibberellin-dependent stem elongation in peas

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.; Sovonick-Dunford, S. A.

1989-01-01

Stem elongation in peas (Pisum sativum L.) is under partial control by gibberellins, yet the mechanism of such control is uncertain. In this study, we examined the cellular and physical properties that govern stem elongation, to determine how gibberellins influence pea stem growth. Stem elongation of etiolated seedlings was retarded with uniconozol, a gibberellin synthesis inhibitor, and the growth retardation was reversed by exogenous gibberellin. Using the pressure probe and vapor pressure osmometry, we found little effect of uniconozol and gibberellin on cell turgor pressure or osmotic pressure. In contrast, these treatments had major effects on in vivo stress relaxation, measured by turgor relaxation and pressure-block techniques. Uniconozol-treated plants exhibited reduced wall relaxation (both initial rate and total amount). The results show that growth retardation is effected via a reduction in the wall yield coefficient and an increase in the yield threshold. These effects were largely reversed by exogenous gibberellin. When we measured the mechanical characteristics of the wall by stress/strain (Instron) analysis, we found only minor effects of uniconozol and gibberellin on the plastic compliance. This observation indicates that these agents did not alter wall expansion through effects on the mechanical (viscoelastic) properties of the wall. Our results suggest that wall expansion in peas is better viewed as a chemorheological, rather than a viscoelastic, process.

Single Nucleotide Polymorphisms of Stemness Genes Predicted to Regulate RNA Splicing, microRNA and Oncogenic Signaling are Associated with Prostate Cancer Survival.

PubMed

Freedman, Jennifer A; Wang, Yanru; Li, Xuechan; Liu, Hongliang; Moorman, Patricia G; George, Daniel J; Lee, Norman H; Hyslop, Terry; Wei, Qingyi; Patierno, Steven R

2018-05-03

Prostate cancer is a clinically and molecularly heterogeneous disease, with variation in outcomes only partially predicted by grade and stage. Additional tools to distinguish indolent from aggressive disease are needed. Phenotypic characteristics of stemness correlate with poor cancer prognosis. Given this correlation, we identified single nucleotide polymorphisms (SNPs) of stemness-related genes and examined their associations with prostate cancer survival. SNPs within stemness-related genes were analyzed for association with overall survival of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Significant SNPs predicted to be functional were selected for linkage disequilibrium analysis and combined and stratified analyses. Identified SNPs were evaluated for association with gene expression. SNPs of CD44 (rs9666607), ABCC1 (rs35605 and rs212091) and GDF15 (rs1058587) were associated with prostate cancer survival and predicted to be functional. A role for rs9666607 of CD44 and rs35605 of ABCC1 in RNA splicing regulation, rs212091 of ABCC1 in miRNA binding site activity and rs1058587 of GDF15 in causing an amino acid change was predicted. These SNPs represent potential novel prognostic markers for overall survival of prostate cancer and support a contribution of the stemness pathway to prostate cancer patient outcome.

In silico modelling of radiation effects towards personalised treatment in radiotherapy

NASA Astrophysics Data System (ADS)

Marcu, Loredana G.; Marcu, David

2017-12-01

In silico models applied in medical physics are valuable tools to assist in treatment optimization and personalization, which represent the ultimate goal of today's radiotherapy. Next to several biological and biophysical factors that influence tumour response to ionizing radiation, hypoxia and cancer stem cells are critical parameters that dictate the final outcome. The current work presents the results of an in silico model of tumour growth and response to radiation developed using Monte Carlo techniques. We are presenting the impact of partial oxygen tension and repopulation via cancer stem cells on tumour control after photon irradiation, highlighting some of the gaps that clinical research needs to fill for better customized treatment.

First-trimester sonographic findings associated with a Dandy-Walker malformation and inferior vermian hypoplasia.

PubMed

Bornstein, Eran; Goncalves Rodríguez, José Luis; Álvarez Pavón, Erika Carolina; Quiroga, Héctor; Or, Drorit; Divon, Michael Y

2013-10-01

We report 2 cases in which first-trimester measurements of the intracranial translucency and the brain stem-to-occipital bone diameter were markedly enlarged. This finding was thought to represent an abnormal fourth ventricle-cisterna magna complex. Subsequently, the diagnoses of a Dandy-Walker malformation with partial vermian agenesis in 1 case and inferior vermian hypoplasia in the other were established and confirmed by either postmortem autopsy or postnatal magnetic resonance imaging. These cases suggest that evaluation of the fourth ventricle-cisterna magna complex, by measuring the intracranial translucency or brain stem-to-occipital bone diameter may identify some cases with structural malformations of the cerebellum as early as the first trimester.

Long-Term Effects of Stem Cells on Total-Body Irradiated Mice

NASA Astrophysics Data System (ADS)

Vyalkina, M. V.; Alchinova, I. B.; Yakovenko, E. N.; Medvedeva, Yu S.; Saburina, I. N.; Karganov, M. Yu

2017-01-01

C57Bl/6 mice were exposed to γ-radiation in a sublethal dose of 7.5 Gy. In 3 hours injection 106/mouse of bone marrow multipotent mesenchymal stromal cells stem cells intravenously to experimental group was done. Methods used: body weight measurement, open field behavior, subfraction composition of blood serum (laser correlation spectroscopy, LCS), histological examination of the spleen, liver, and pancreas, count of T and B cells, white blood formula. After 1.5 and 3 months the general trend towards intermediate position of the parameters observed in the experimental between those in intact and irradiated controls attests to partial protective/restorative effects of the injected cells.

Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

PubMed

Bhatt, Vijaya Raj; Vose, Julie M

2014-12-01

Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. Copyright © 2014 Elsevier Inc. All rights reserved.

Promoting professional identity, motivation, and persistence: Benefits of an informal mentoring program for female undergraduate students

PubMed Central

Bloodhart, Brittany; Barnes, Rebecca T.; Adams, Amanda S.; Clinton, Sandra M.; Pollack, Ilana; Godfrey, Elaine; Burt, Melissa; Fischer, Emily V.

2017-01-01

Women are underrepresented in a number of science, technology, engineering, and mathematics (STEM) disciplines. Limited diversity in the development of the STEM workforce has negative implications for scientific innovation, creativity, and social relevance. The current study reports the first-year results of the PROmoting Geoscience Research, Education, and SuccesS (PROGRESS) program, a novel theory-driven informal mentoring program aimed at supporting first- and second-year female STEM majors. Using a prospective, longitudinal, multi-site (i.e., 7 universities in Colorado/Wyoming Front Range & Carolinas), propensity score matched design, we compare mentoring and persistence outcomes for women in and out of PROGRESS (N = 116). Women in PROGRESS attended an off-site weekend workshop and gained access to a network of volunteer female scientific mentors from on- and off-campus (i.e., university faculty, graduate students, and outside scientific professionals). The results indicate that women in PROGRESS had larger networks of developmental mentoring relationships and were more likely to be mentored by faculty members and peers than matched controls. Mentoring support from a faculty member benefited early-undergraduate women by strengthening their scientific identity and their interest in earth and environmental science career pathways. Further, support from a faculty mentor had a positive indirect impact on women’s scientific persistence intentions, through strengthened scientific identity development. These results imply that first- and second- year undergraduate women’s mentoring support networks can be enhanced through provision of protégé training and access to more senior women in the sciences willing to provide mentoring support. PMID:29091969

Umbilical Cord Blood Transplantation Supported by Third Party Donor Cells: Rationale, Results and Applications

PubMed Central

van Besien, Koen; Liu, Hongtao; Jain, Nitin; Stock, Wendy; Artz, Andrew

2012-01-01

Low incidence of GVHD provides the major rational for pursuing UCB stem cell transplant (UCB SCT). Considerable evidence also suggests a lower rate of recurrence after UCB SCT than after transplantation from adult donors. Recent advances in understanding of the human fetal immune development provide a rational underpinning for these clinical outcomes. The fetal immune system is geared toward maintaining tolerance to foreign antigens, particularly to the maternal antigens to which it is exposed throughout gestation. To this purpose it is dominated by a unique population of peripheral T regulatory cells which actively maintain tolerance. This and other features of the UCB lymphoid system explains the low incidence of GVHD and superior outcomes of UCB SCT with NIMA (non-inherited maternal antigens)-matched grafts. At the same time, highly sensitized maternal microchimeric cells are frequently detected in UCB and likely contribute to superior GVL effects and low rates of disease recurrence in IPA (inherited paternal antigen) matched UCB recipients. But historically erratic and slow hematopoietic recovery after UCB SCT leads to increased early morbidity and mortality, excessive hospitalization and costs. This has held up the widespread utilization of UCB SCT in adults. Here we summarize recent data on UCB SCT with an emphasis on studies of co-infusion of adult CD34 selected hematopoietic stem cells with UCB SCT. This procedure, through transient engraftment of adult hematopoietic stem cells largely overcomes the problem of delayed engraftment. We also briefly discuss unresolved issues and possible future applications of this technology. PMID:23142329

Promoting professional identity, motivation, and persistence: Benefits of an informal mentoring program for female undergraduate students.

PubMed

Hernandez, Paul R; Bloodhart, Brittany; Barnes, Rebecca T; Adams, Amanda S; Clinton, Sandra M; Pollack, Ilana; Godfrey, Elaine; Burt, Melissa; Fischer, Emily V

2017-01-01

Women are underrepresented in a number of science, technology, engineering, and mathematics (STEM) disciplines. Limited diversity in the development of the STEM workforce has negative implications for scientific innovation, creativity, and social relevance. The current study reports the first-year results of the PROmoting Geoscience Research, Education, and SuccesS (PROGRESS) program, a novel theory-driven informal mentoring program aimed at supporting first- and second-year female STEM majors. Using a prospective, longitudinal, multi-site (i.e., 7 universities in Colorado/Wyoming Front Range & Carolinas), propensity score matched design, we compare mentoring and persistence outcomes for women in and out of PROGRESS (N = 116). Women in PROGRESS attended an off-site weekend workshop and gained access to a network of volunteer female scientific mentors from on- and off-campus (i.e., university faculty, graduate students, and outside scientific professionals). The results indicate that women in PROGRESS had larger networks of developmental mentoring relationships and were more likely to be mentored by faculty members and peers than matched controls. Mentoring support from a faculty member benefited early-undergraduate women by strengthening their scientific identity and their interest in earth and environmental science career pathways. Further, support from a faculty mentor had a positive indirect impact on women's scientific persistence intentions, through strengthened scientific identity development. These results imply that first- and second- year undergraduate women's mentoring support networks can be enhanced through provision of protégé training and access to more senior women in the sciences willing to provide mentoring support.

[Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia].

PubMed

Wang, Li; Wu, Ya-Mei; Cao, Yong-Bin; Li, Xiao-Hong; Xu, Li-Xin; Wang, Hai-Tao; Gao, Ya-Hui; Wu, Xiao-Xiong

2016-12-01

To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning. The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells. All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58). After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.

Femoral stem incorporating a diamond cubic lattice structure: Design, manufacture and testing.

PubMed

Jetté, Bruno; Brailovski, Vladimir; Dumas, Mathieu; Simoneau, Charles; Terriault, Patrick

2018-01-01

The current total hip prostheses with dense femoral stems are considerably stiffer than the host bones, which leads to such long-term complications as aseptic loosening, and eventually, the need for a revision. Consequently, the lifetime of the implantation does not match the lifetime expectation of young patients. A femoral stem design featuring a porous structure is proposed to lower its stiffness and allow bone tissue ingrowth. The porous structure is based on a diamond cubic lattice in which the pore size and the strut thickness are selected to meet the biomechanical requirements of the strength and the bone ingrowth. A porous stem and its fully dense counterpart are produced by laser powder-bed fusion using Ti-6Al-4V alloy. To evaluate the stiffness reduction, static testing based on the ISO standard 7206-4 is performed. The experimental results recorded by digital image correlation are analyzed and compared to the numerical model. The numerical and experimental force-displacement characteristics of the porous stem show a 31% lower stiffness as compared to that of its dense counterpart. Moreover, the correlation analysis of the total displacement and equivalent strain fields allows the preliminary validation of the numerical model of the porous stem. Finally, the analysis of the surface-to-volume and the strength-to-stiffness ratios of diamond lattice structures allow the assessment of their potential as biomimetic constructs for load-bearing orthopaedic implants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Breath-holding spells may be associated with maturational delay in myelination of brain stem.

PubMed

Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

2014-02-01

To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

Ethylene is not involved in adaptive responses to flooding in the Amazonian wild rice species Oryza grandiglumis.

PubMed

Okishio, Takuma; Sasayama, Daisuke; Hirano, Tatsuya; Akimoto, Masahiro; Itoh, Kazuyuki; Azuma, Tetsushi

2015-02-01

The Amazonian wild rice Oryza grandiglumis has two contrasting adaptation mechanisms to flooding submergence: a quiescence response to complete submergence at the seedling stage and an escape response based on internodal elongation to partial submergence at the mature stage. We investigated possible factors that trigger these responses. In stem segments excised from mature O. grandiglumis plants, complete submergence only slightly promoted internodal elongation with increased ethylene levels in the internodes, while partial submergence substantially promoted internodal elongation without increased ethylene levels in the internodes. Incubation of non-submerged stem segments under a continuous flow of humidified ethylene-free air promoted internodal elongation to the same extent as that observed for partially submerged segments. Applied ethylene had little effect on the internodal elongation of non-submerged segments irrespective of humidity conditions. These results indicate that the enhanced internodal elongation of submerged O. grandiglumis plants is not triggered by ethylene accumulated during submergence but by the moist surroundings provided by submergence. The growth of shoots in O. grandiglumis seedlings was not promoted by ethylene or complete submergence, as is the case in O. sativa cultivars possessing the submergence-tolerant gene SUB1A. However, because the genome of O. grandiglumis lacks the SUB1A gene, the quiescence response of O. grandiglumis seedlings to complete submergence may be regulated by a mechanism distinct from that involved in the response of submergence-tolerant O. sativa cultivars. Copyright © 2014 Elsevier GmbH. All rights reserved.

Challenges of stem cell-based pulp and dentin regeneration: a clinical perspective.

PubMed

Huang, George T-J; Al-Habib, Mey; Gauthier, Philippe

2013-03-01

There are two types of approaches to regenerate tissues: cell-based and cell-free. The former approach is to introduce exogenous cells into the host to regenerate tissues, and the latter is to use materials other than cells in an attempt to regenerate tissues. There has been a significant advancement in stem cell-based pulp and dentin regeneration research in the past few years. Studies in small and large animals have demonstrated that pulp/dentin-like tissues can be regenerated partially or completely in the root canal space with apical openings of 0.7-3.0 mm using dental pulp stem cells, including stem cells from apical papilla (SCAP) and subpopulations of pulp stem cells. Bone marrow mesenchymal stem cells (BMMSCs) and adipose tissue-derived MSCs (ADMSCs) have also been shown to regenerate pulp-like tissue. In contrast, the cell-free approach has not produced convincing evidence on pulp regeneration. However, one crucial concept has not been considered nor defined in the field of pulp/dentin regeneration and that is the critical size defect of dentin and pulp. Without such consideration and definition, it is difficult to predict or anticipate the extent of cell-free pulp regeneration that would occur. By reasoning, cell-free therapy is unlikely to regenerate an organ/tissue after total loss. Similarly, after a total loss of pulp, it is unlikely to regenerate without using exogenously introduced cells. A cell homing approach may provide a limited amount of tissue regeneration. Although stem cell-based pulp/dentin regeneration has shown great promise, clinical trials are difficult to launch at present. This article will address several issues that challenge and hinder the clinical applications of pulp/dentin regeneration which need to be overcome before stem cell-based pulp/dentin regeneration can occur in the clinic.

Challenges of stem cell-based pulp and dentin regeneration: a clinical perspective

PubMed Central

HUANG, GEORGE T.-J.; AL-HABIB, MEY; GAUTHIER, PHILIPPE

2013-01-01

There are two types of approaches to regenerate tissues: cell-based and cell-free. The former approach is to introduce exogenous cells into the host to regenerate tissues, and the latter is to use materials other than cells in an attempt to regenerate tissues. There has been a significant advancement in stem cell-based pulp and dentin regeneration research in the past few years. Studies in small and large animals have demonstrated that pulp/dentin-like tissues can be regenerated partially or completely in the root canal space with apical openings of 0.7-3.0 mm using dental pulp stem cells, including stem cells from apical papilla (SCAP) and subpopulations of pulp stem cells. Bone marrow mesenchymal stem cells (BMMSCs) and adipose tissue-derived MSCs (ADMSCs) have also been shown to regenerate pulp-like tissue. In contrast, the cell-free approach has not produced convincing evidence on pulp regeneration. However, one crucial concept has not been considered nor defined in the field of pulp/dentin regeneration and that is the critical size defect of dentin and pulp. Without such consideration and definition, it is difficult to predict or anticipate the extent of cell-free pulp regeneration that would occur. By reasoning, cell-free therapy is unlikely to regenerate an organ/tissue after total loss. Similarly, after a total loss of pulp, it is unlikely to regenerate without using exogenously introduced cells. A cell homing approach may provide a limited amount of tissue regeneration. Although stem cell-based pulp/dentin regeneration has shown great promise, clinical trials are difficult to launch at present. This article will address several issues that challenge and hinder the clinical applications of pulp/dentin regeneration which need to be overcome before stem cell-based pulp/dentin regeneration can occur in the clinic. PMID:23914150

Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine

PubMed Central

Madariaga, Maria Lucia L.; Michel, Sebastian G.; La Muraglia, Glenn M.; Sihag, Smita; Leonard, David A.; Farkash, Evan A.; Colvin, Robert B.; Cetrulo, Curtis L.; Huang, Christene A.; Sachs, David H.; Madsen, Joren C.; Allan, James S.

2014-01-01

Background Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. Here we tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. Methods In the experimental group (Group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were MHC-matched to the recipients (n=3). In the control group (Group 2), both the donor parenchyma and the passenger leukocytes were MHC-mismatched to the recipients (n = 3). Results Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (Group 1) survived on average 107 days (range 80–156). Control lung allografts (Group 2) survived on average 45 days (range 29–64; p<0.05). Conclusion Our data indicate that recipient-matching of passenger leukocytes significantly prolongs lung allograft survival. PMID:25757217

Recognition of partially occluded threat objects using the annealed Hopefield network

NASA Technical Reports Server (NTRS)

Kim, Jung H.; Yoon, Sung H.; Park, Eui H.; Ntuen, Celestine A.

1992-01-01

Recognition of partially occluded objects has been an important issue to airport security because occlusion causes significant problems in identifying and locating objects during baggage inspection. The neural network approach is suitable for the problems in the sense that the inherent parallelism of neural networks pursues many hypotheses in parallel resulting in high computation rates. Moreover, they provide a greater degree of robustness or fault tolerance than conventional computers. The annealed Hopfield network which is derived from the mean field annealing (MFA) has been developed to find global solutions of a nonlinear system. In the study, it has been proven that the system temperature of MFA is equivalent to the gain of the sigmoid function of a Hopfield network. In our early work, we developed the hybrid Hopfield network (HHN) for fast and reliable matching. However, HHN doesn't guarantee global solutions and yields false matching under heavily occluded conditions because HHN is dependent on initial states by its nature. In this paper, we present the annealed Hopfield network (AHN) for occluded object matching problems. In AHN, the mean field theory is applied to the hybird Hopfield network in order to improve computational complexity of the annealed Hopfield network and provide reliable matching under heavily occluded conditions. AHN is slower than HHN. However, AHN provides near global solutions without initial restrictions and provides less false matching than HHN. In conclusion, a new algorithm based upon a neural network approach was developed to demonstrate the feasibility of the automated inspection of threat objects from x-ray images. The robustness of the algorithm is proved by identifying occluded target objects with large tolerance of their features.

Effects of asynchrony and ear of presentation on the pitch of mistuned partials in harmonic and frequency-shifted complex tones.

PubMed

Brunstrom, J M; Roberts, B

2001-07-01

When a partial of a periodic complex is mistuned, its change in pitch is greater than expected. Two experiments examined whether these partial-pitch shifts are related to the computation of global pitch. In experiment 1, stimuli were either harmonic or frequency-shifted (25% of F0) complexes. One partial was mistuned by +/- 4% and played with leading and lagging portions of 500 ms each, relative to the other components (1 s), in both monaural and dichotic contexts. Subjects indicated whether the mistuned partial was higher or lower in pitch when concurrent with the other components. Responses were positively correlated with the direction of mistuning in all conditions. In experiment 2, stimuli from each condition were compared with synchronous equivalents. Subjects matched a pure tone to the pitch of the mistuned partial (component 4). The results showed that partial-pitch shifts are not reduced in size by asynchrony. Similar asynchronies are known to produce a near-exclusion of a mistuned partial from the global-pitch computation. This mismatch indicates that global and partial pitch are derived from different processes. The similarity of the partial-pitch shifts observed for harmonic and frequency-shifted stimuli suggests that they arise from a grouping mechanism that is sensitive to spectral regularity.

Sources of interference in item and associative recognition memory.

PubMed

Osth, Adam F; Dennis, Simon

2015-04-01

A powerful theoretical framework for exploring recognition memory is the global matching framework, in which a cue's memory strength reflects the similarity of the retrieval cues being matched against the contents of memory simultaneously. Contributions at retrieval can be categorized as matches and mismatches to the item and context cues, including the self match (match on item and context), item noise (match on context, mismatch on item), context noise (match on item, mismatch on context), and background noise (mismatch on item and context). We present a model that directly parameterizes the matches and mismatches to the item and context cues, which enables estimation of the magnitude of each interference contribution (item noise, context noise, and background noise). The model was fit within a hierarchical Bayesian framework to 10 recognition memory datasets that use manipulations of strength, list length, list strength, word frequency, study-test delay, and stimulus class in item and associative recognition. Estimates of the model parameters revealed at most a small contribution of item noise that varies by stimulus class, with virtually no item noise for single words and scenes. Despite the unpopularity of background noise in recognition memory models, background noise estimates dominated at retrieval across nearly all stimulus classes with the exception of high frequency words, which exhibited equivalent levels of context noise and background noise. These parameter estimates suggest that the majority of interference in recognition memory stems from experiences acquired before the learning episode. (c) 2015 APA, all rights reserved).

Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases.

PubMed

Narisawa, Yutaka; Koba, Shinichi; Inoue, Takuya; Nagase, Kotaro

2015-05-01

The histogenesis of Merkel cell carcinoma (MCC) has remained unresolved. Moreover, one of the questions is whether pure MCC and combined MCC represent the same histogenesis and entity. The existence of combined MCC suggests that MCC likely arise from pluripotent stem cells. Merkel cells (MC) localize within the bulge area, which is populated by hair follicle stem cells. We used hair follicle stem cell markers to investigate whether MCC share certain characteristics of these stem cells. Fourteen MCC specimens were examined histologically and immunohistochemically. There were six pure MCC and eight combined MCC. In six combined MCC, both MCC components and squamous components at least focally shared the expression of one or more of cytokeratin (CK)15, CK19 and CD200, which are hair follicle stem cell markers. On the other hand, four cases of pure MCC showed partially distinct CK19 expression, but did not show CK15 and/or CD200 expression. There was a distinct difference between pure MCC and combined MCC on the expression of hair follicle stem cell markers. The normal skin expressed CK15, CK19 and CD200 in the bulge area, whereas CK15 and CD200 were absent in the MC-rich glabrous skin and touch domes. The results led us to hypothesize that combined MCC originate from the hair follicle stem cells. We postulate that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells. Further investigation is warranted to confirm the histogenesis of pure MCC and combined MCC. © 2015 Japanese Dermatological Association.

Spectroscopic characterization of enzymatic flax retting: Factor analysis of FT-IR and FT-Raman data

NASA Astrophysics Data System (ADS)

Archibald, D. D.; Henrikssen, G.; Akin, D. E.; Barton, F. E.

1998-06-01

Flax retting is a chemical, microbial or enzymatic process which releases the bast fibers from the stem matrix so they can be suitable for mechanical processing before spinning into linen yarn. This study aims to determine the vibrational spectral features and sampling methods which can be used to evaluate the retting process. Flax stems were retted on a small scale using an enzyme mixture known to yield good retted flax. Processed stems were harvested at various time points in the process and the retting was evaluated by conventional methods including weight loss, color difference and Fried's test, a visual ranking of how the stems disintegrate in hot water. Spectroscopic measurements were performed on either whole stems or powders of the fibers that were mechanically extracted from the stems. Selected regions of spectra were baseline and amplitude corrected using a variant of the multiplicative signal correction method. Principal component regression and partial least-squares regression with full cross-validation were used to determine the spectral features and rate of spectral transformation by regressing the spectra against the retting time in hours. FT-Raman of fiber powders and FT-IR reflectance of whole stems were the simplest and most precise methods for monitoring the retting transformation. Raman tracks the retting by measuring the decrease in aromatic signal and subtle changes in the C-H stretching vibrations. The IR method uses complex spectral features in the fingerprint and carbonyl region, many of which are due to polysaccharide components. Both spectral techniques monitor the retting process with greater precision than the reference method.

Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation.

PubMed

Kanda, Junya

2016-01-01

The Transplant Registry Unified Management Program (TRUMP) made it possible for members of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) to analyze large sets of national registry data on autologous and allogeneic hematopoietic stem cell transplantation. However, as the processes used to collect transplantation information are complex and differed over time, the background of these processes should be understood when using TRUMP data. Previously, information on the HLA locus of patients and donors had been collected using a questionnaire-based free-description method, resulting in some input errors. To correct minor but significant errors and provide accurate HLA matching data, the use of a Stata or EZR/R script offered by the JSHCT is strongly recommended when analyzing HLA data in the TRUMP dataset. The HLA mismatch direction, mismatch counting method, and different impacts of HLA mismatches by stem cell source are other important factors in the analysis of HLA data. Additionally, researchers should understand the statistical analyses specific for hematopoietic stem cell transplantation, such as competing risk, landmark analysis, and time-dependent analysis, to correctly analyze transplant data. The data center of the JSHCT can be contacted if statistical assistance is required.

Scientists not Sponges: STEM Interest and Inquiry in Early Childhood

NASA Astrophysics Data System (ADS)

Jipson, J. L.; Callanan, M. A.; Schultz, G.; Hurst, A.

2014-07-01

Young children are fascinated by the natural world. They explore endlessly, with both a sense of wonder and determination, usually in self-directed investigations or informal interactions with peers and adults. Capitalizing on this early period of spontaneous interest and inquiry is critical to efforts to promote lifelong STEM literacy. To inform education and public outreach efforts, it is important to consider common assumptions about how children of this age learn and consider how such assumptions influence the ways we support children's learning. Four metaphors for children learning are investigated in this paper: the young child as sponge, the young child as unlit match, the young child as scientist, and the young child as apprentice. As we critically evaluate these views on learning, we share research findings from developmental psychology that demonstrate that children's engagement with STEM begins well before kindergarten, that children between three and five years of age develop surprisingly sophisticated scientific reasoning capacities and conceptual knowledge, and that parents play an important role in structuring and supporting preschool children's learning.

Online induction heating for determination of isotope composition of woody stem water with laser spectrometry: A methods assessment

USGS Publications Warehouse

Lazarus, Brynne E.; Germino, Matthew; Vander Veen, Jessica L.

2016-01-01

Application of stable isotopes of water to studies of plant–soil interactions often requires a substantial preparatory step of extracting water from samples without fractionating isotopes. Online heating is an emerging approach for this need, but is relatively untested and major questions of how to best deliver standards and assess interference by organics have not been evaluated. We examined these issues in our application of measuring woody stem xylem of sagebrush using a Picarro laser spectrometer with online induction heating. We determined (1) effects of cryogenic compared to induction-heating extraction, (2) effects of delivery of standards on filter media compared to on woody stem sections, and (3) spectral interference from organic compounds for these approaches (and developed a technique to do so). Our results suggest that matching sample and standard media improves accuracy, but that isotopic values differ with the extraction method in ways that are not due to spectral interference from organics.

Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation

PubMed Central

Sleep, Eduard; McClendon, Mark T.; Preslar, Adam T.; Chen, Charlotte H.; Sangji, M. Hussain; Pérez, Charles M. Rubert; Haynes, Russell D.; Meade, Thomas J.; Blau, Helen M.; Stupp, Samuel I.

2017-01-01

Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice. PMID:28874575

Gene therapy for sickle cell disease: An update.

PubMed

Demirci, Selami; Uchida, Naoya; Tisdale, John F

2018-05-30

Sickle cell disease (SCD) is one of the most common life-threatening monogenic diseases affecting millions of people worldwide. Allogenic hematopietic stem cell transplantation is the only known cure for the disease with high success rates, but the limited availability of matched sibling donors and the high risk of transplantation-related side effects force the scientific community to envision additional therapies. Ex vivo gene therapy through globin gene addition has been investigated extensively and is currently being tested in clinical trials that have begun reporting encouraging data. Recent improvements in our understanding of the molecular pathways controlling mammalian erythropoiesis and globin switching offer new and exciting therapeutic options. Rapid and substantial advances in genome engineering tools, particularly CRISPR/Cas9, have raised the possibility of genetic correction in induced pluripotent stem cells as well as patient-derived hematopoietic stem and progenitor cells. However, these techniques are still in their infancy, and safety/efficacy issues remain that must be addressed before translating these promising techniques into clinical practice. Published by Elsevier Inc.

PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients

PubMed Central

Ussowicz, Marek; Rybka, Blanka; Wendycz-Domalewska, Danuta; Ryczan, Renata; Gorczyńska, Ewa; Kałwak, Krzysztof; Woźniak, Mieczysław

2010-01-01

After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations. PMID:20848295

Development of autologous blood cell therapies

PubMed Central

Kim, Ah Ram; Sankaran, Vijay G.

2016-01-01

Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are commonly performed in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. In addition, such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. PMID:27345108

Normal Performance in Non-Visual Social Cognition Tasks in Women with Turner Syndrome.

PubMed

Anaki, David; Zadikov-Mor, Tal; Gepstein, Vardit; Hochberg, Ze'ev

2018-01-01

Turner syndrome (TS) is a chromosomal disorder in women resulting from a partial or complete absence of the X chromosome. In addition to physical and hormonal dysfunctions, along with a unique neurocognitive profile, women with TS are reported to suffer from social functioning difficulties. Yet, it is unclear whether these difficulties stem from impairments in social cognition per se or from other deficits that characterize TS but are not specific to social cognition. Previous research that has probed social functioning in TS is equivocal regarding the source of these psychosocial problems since they have mainly used tasks that were dependent on visual-spatial skills, which are known to be compromised in TS. In the present study, we tested 26 women with TS and 26 matched participants on three social cognition tasks that did not require any visual-spatial capacities but rather relied on auditory-verbal skills. The results revealed that in all three tasks the TS participants did not differ from their control counterparts. The same TS cohort was found, in an earlier study, to be impaired, relative to controls, in other social cognition tasks that were dependent on visual-spatial skills. Taken together these findings suggest that the social problems, documented in TS, may be related to non-specific spatial-visual factors that affect their social cognition skills.

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma.

PubMed

Schober, Sebastian J; von Luettichau, Irene; Wawer, Angela; Steinhauser, Maximilian; Salat, Christoph; Schwinger, Wolfgang; Ussowicz, Marek; Antunovic, Petar; Castagna, Luca; Kolb, Hans-Jochem; Burdach, Stefan E G; Thiel, Uwe

2018-04-27

Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 × 10 4 to 1 × 10 8 CD3 + cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

Efficient automatic OCR word validation using word partial format derivation and language model

NASA Astrophysics Data System (ADS)

Chen, Siyuan; Misra, Dharitri; Thoma, George R.

2010-01-01

In this paper we present an OCR validation module, implemented for the System for Preservation of Electronic Resources (SPER) developed at the U.S. National Library of Medicine.1 The module detects and corrects suspicious words in the OCR output of scanned textual documents through a procedure of deriving partial formats for each suspicious word, retrieving candidate words by partial-match search from lexicons, and comparing the joint probabilities of N-gram and OCR edit transformation corresponding to the candidates. The partial format derivation, based on OCR error analysis, efficiently and accurately generates candidate words from lexicons represented by ternary search trees. In our test case comprising a historic medico-legal document collection, this OCR validation module yielded the correct words with 87% accuracy and reduced the overall OCR word errors by around 60%.

Coupling of solute transport and cell expansion in pea stems

NASA Technical Reports Server (NTRS)

Schmalstig, J. G.; Cosgrove, D. J.

1990-01-01

As cells expand and are displaced through the elongation zone of the epicotyl of etiolated pea (Pisum sativum L. var Alaska) seedlings, there is little net dilution of the cell sap, implying a coordination between cell expansion and solute uptake from the phloem. Using [14C] sucrose as a phloem tracer (applied to the hypogeous cotyledons), the pattern of label accumulation along the stem closely matched the growth rate pattern: high accumulation in the growing zone, little accumulation in nongrowing regions. Several results suggest that a major portion of phloem contents enters elongating cells through the symplast. We propose that the coordination between phloem transport and cell expansion is accomplished via regulatory pathways affecting both plasmodesmata conductivity and cell expansion.

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

PubMed

Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

2018-06-19

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative assessment of brain stem and cerebellar atrophy in spinocerebellar ataxia types 3 and 6: impact on clinical status.

PubMed

Eichler, L; Bellenberg, B; Hahn, H K; Köster, O; Schöls, L; Lukas, C

2011-05-01

Cerebellar and brain stem atrophy are important features in SCA3, whereas SCA6 has been regarded as a "pure" cerebellar disease. However, recent neuropathologic studies have described additional brain stem involvement in SCA6. We, therefore, aimed to investigate the occurrence and impact of regional infratentorial brain volume differences in patients with SCA3 and SCA6. Thirty-four patients with genetically proved SCA (SCA3, n = 17; SCA6, n = 17) and age-matched healthy control subjects (n = 51) were included. In all subjects, high-resolution T1-weighted images were acquired with a 1.5T MR imaging scanner. Individual brain stem and cerebellar volumes were calculated by using semiautomated volumetry approaches. For all patients with SCA, clinical dysfunction was scored according to the ICARS. Multiple regression analysis was used to identify the contribution of regional volumes to explain the variance in clinical dysfunction in each SCA genotype. Cerebellar volumes were lower in patients with SCA6 compared with controls and with those with SCA3. In contrast to controls, brain stem volume loss was observed in patients with SCA3 (P < .001) and, to a lesser extent, in those with SCA6 (P = .027). Significant linear dependencies were found between ICARS and cerebellum volume (SCA3: R(2) = 0.29, P = .02; SCA6: R(2) = 0.29, P = .03) and between ICARS and brain stem volume (SCA3: R(2) = 0.49, P = .002; SCA6: R(2) = 0.39, P < .01) in both subtypes. Both cerebellar and brain stem atrophy contributed independently to the variance in clinical dysfunction in SCA6, while in SCA3, only brain stem atrophy was of relevance. Our current findings in accordance with recent neuroradiologic and pathoanatomic studies suggest brain stem and cerebellar volume loss as attractive surrogate markers of disease severity in SCA3 and SCA6.

Characterization of porcine partially reprogrammed iPSCs from adipose-derived stem cells.

PubMed

Wei, Chao; Li, Xia; Zhang, Pengfei; Zhang, Yu; Liu, Tong; Jiang, Shaoshuai; Han, Fei; Zhang, Yunhai

2015-05-01

Partially reprogrammed induced pluripotent stem cells (PiPSCs) have great potential for investigating reprogramming mechanisms and represent an alternative potential material for making genetically modified animals and regenerative medicine. To date, PiPSCs have scarcely been reported in detail when compared with mice and humans. In this study, we obtained PiPSCs from porcine adipose-derived stem cells (pADSCs) by ectopic expression of human transcription factors (OCT4, SOX2, c-MYC, and KLF4) in feeder-free condition. The morphology and proliferation activity of porcine PiPSCs (pPiPSCs) were similar to those of porcine fully reprogrammed iPSCs (pFiPSCs); furthermore, pPiPSCs expressed higher levels of the typical surface molecules (CD29) found in pADSCs. However, pPiPSCs were negative for key proteins (NANOG) connected with stemness and possessed lower differentiation ability in vivo and in vitro. When differentiation-inhibiting factors were withdrawn, pPiPSCs-derived cells (pPiPSC-DCs) showed similar features to pADSCs in many aspects, including proliferation, differentiation, and immunosuppression. When both types of cells were used to produce cloned embryos, we found that the blastocyst formation rate of 19DC (one of the pPiPSC-DC cell lines)-derived cloned embryos was obviously higher than that of others. The total cell number of 19DC-derived blastocysts was significantly higher than the 30DC (one pFiPSC-DC cell line)-derived blastocysts. In all, through limited differentiation ability, the proliferation activity of pPiPSCs is similar to that of pFiPSCs, and pPiPSCs can retain several of the features of pADSCs, which are beneficial to cell therapy. Furthermore, the differentiation of pPiPSCs is more favorable for producing high-quality reconstructed embryos. © 2015 Society for Reproduction and Fertility.

Overcoming the response plateau in multiple myeloma: A novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization

PubMed Central

Niesvizky, Ruben; Mark, Tomer M.; Ward, Maureen; Jayabalan, David S.; Pearse, Roger N.; Manco, Megan; Stern, Jessica; Christos, Paul J.; Mathews, Lena; Shore, Tsiporah B.; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E.

2014-01-01

Purpose This phase 2 study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible myeloma patients who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Experimental design Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells post-bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. Results The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; post-mobilization response rate was 96%, including 48% ≥VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 106 cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation;5-year overall survival rate was 76.4%. Grade ≥3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Conclusion Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield. PMID:23357980

Automated sequence-specific protein NMR assignment using the memetic algorithm MATCH.

PubMed

Volk, Jochen; Herrmann, Torsten; Wüthrich, Kurt

2008-07-01

MATCH (Memetic Algorithm and Combinatorial Optimization Heuristics) is a new memetic algorithm for automated sequence-specific polypeptide backbone NMR assignment of proteins. MATCH employs local optimization for tracing partial sequence-specific assignments within a global, population-based search environment, where the simultaneous application of local and global optimization heuristics guarantees high efficiency and robustness. MATCH thus makes combined use of the two predominant concepts in use for automated NMR assignment of proteins. Dynamic transition and inherent mutation are new techniques that enable automatic adaptation to variable quality of the experimental input data. The concept of dynamic transition is incorporated in all major building blocks of the algorithm, where it enables switching between local and global optimization heuristics at any time during the assignment process. Inherent mutation restricts the intrinsically required randomness of the evolutionary algorithm to those regions of the conformation space that are compatible with the experimental input data. Using intact and artificially deteriorated APSY-NMR input data of proteins, MATCH performed sequence-specific resonance assignment with high efficiency and robustness.

Nested case-control studies: should one break the matching?

PubMed

Borgan, Ørnulf; Keogh, Ruth

2015-10-01

In a nested case-control study, controls are selected for each case from the individuals who are at risk at the time at which the case occurs. We say that the controls are matched on study time. To adjust for possible confounding, it is common to match on other variables as well. The standard analysis of nested case-control data is based on a partial likelihood which compares the covariates of each case to those of its matched controls. It has been suggested that one may break the matching of nested case-control data and analyse them as case-cohort data using an inverse probability weighted (IPW) pseudo likelihood. Further, when some covariates are available for all individuals in the cohort, multiple imputation (MI) makes it possible to use all available data in the cohort. In the paper we review the standard method and the IPW and MI approaches, and compare their performance using simulations that cover a range of scenarios, including one and two endpoints.

Partial rootzone drying (PRD) and regulated deficit irrigation (RDI) effects on stomal conductance, growth, photosynthetic capacity, and water-use efficiency of papaya

USDA-ARS?s Scientific Manuscript database

Papaya (Carica papaya, L.) is an important economic crop in tropical and subtropical countries in addition to its human health benefits. Papaya is a giant herbaceous species and maintaining adequate tissue turgidity and water availability is necessary to maintain the rigidity of the stem as well as...

Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch.

PubMed

López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca; Guiu, Jordi; Iglesias, Mar; Roman, Angel Carlos; Gutarra, Susana; González, Susana; Muñoz-Cánoves, Pura; Fernández-Salguero, Pedro; Radtke, Freddy; Bigas, Anna; Espinosa, Lluís

2015-01-01

Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. To address this issue, we have generated composite tamoxifen-inducible intestine-specific genetic mouse models and analyzed the expression of intestinal differentiation markers. Importantly, we found that activation of β-catenin partially rescues the differentiation phenotype of Rbpj deletion mutants, but not the loss of the ISC compartment. Moreover, we identified Bmi1, which is expressed in the ISC and progenitor compartments, as a gene that is co-regulated by Notch and β-catenin. Loss of Bmi1 resulted in reduced proliferation in the ISC compartment accompanied by p16(INK4a) and p19(ARF) (splice variants of Cdkn2a) accumulation, and increased differentiation to the post-mitotic goblet cell lineage that partially mimics Notch loss-of-function defects. Finally, we provide evidence that Bmi1 contributes to ISC self-renewal. © 2015. Published by The Company of Biologists Ltd.

Subepithelial corneal fibrosis partially due to epithelial-mesenchymal transition of ocular surface epithelium

PubMed Central

Kawashima, Motoko; Higa, Kazunari; Satake, Yoshiyuki; Omoto, Masahiro; Tsubota, Kazuo; Shimmura, Shigeto; Shimazaki, Jun

2010-01-01

Purpose To determine whether epithelial-mesenchymal transition is involved in the development of corneal subepithelial fibrosis (pannus). Methods Frozen samples of pannus tissue removed from human corneas with a diagnosis of total limbal stem cell deficiency were characterized by immunostaining for both epithelial and mesenchymal markers. We selected transformation-related protein 63 (p63) and pancytokeratin as epithelial markers and vimentin and α-smooth muscle actin (α-SMA) as mesenchymal markers. Immunostaining for β-catenin and E-cadherin was performed to determine wingless-Int (Wnt)-pathway activation. RT–PCR analysis was also performed on epithelial tissue obtained from pannus samples after dispase digestion. Results Immunohistochemistry revealed strong nuclear expression of p63 and weak intercellular expression of E-cadherin in epithelial basal cells of pannus tissue. Furthermore, translocation of β-catenin from intercellular junctions to the nucleus and cytoplasm was also observed. Double-positive cells for both p63 and α-SMA were observed in the subepithelial stroma of pannus tissue, which was supported by RT–PCR and cytospin analysis. Conclusions Epithelial-mesenchymal transition may be partially involved in the development of subepithelial corneal fibrosis due to total limbal stem cell deficiency. PMID:21179238

Usp16 contributes to somatic stem cell defects in Down syndrome

PubMed Central

Adorno, Maddalena; Sikandar, Shaheen; Mitra, Siddhartha S.; Kuo, Angera; Di Robilant, Benedetta Nicolis; Haro-Acosta, Veronica; Ouadah, Youcef; Quarta, Marco; Rodriguez, Jacqueline; Qian, Dalong; Reddy, Vadiyala M.; Cheshier, Samuel; Garner, Craig C.; Clarke, Michael F.

2013-01-01

SUMMARY Down syndrome (DS) results from full or partial trisomy of chromosome 21. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. Here we show that in Ts65Dn mice, trisomic for 132 genes homologous to HSA21, triplication of Usp16 reduces self-renewal of hematopoietic stem cells and expansion of mammary epithelial cells, neural progenitors, and fibroblasts. Moreover, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. Usp16 can remove ubiquitin from H2AK119, a critical mark for the maintenance of multiple somatic tissues. Downregulation of Usp16, either by mutation of a single normal USP16 allele or by shRNAs, largely rescues all these defects. Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and post-natal neural progenitors while downregulation of USP16 partially rescues the proliferation defects of DS fibroblasts. Taken together, these results suggest that USP16 plays an important role in antagonizing the self-renewal and/or senescence pathways in Down syndrome and could serve as an attractive target to ameliorate some of the associated pathologies. PMID:24025767

Surface topography during neural stem cell differentiation regulates cell migration and cell morphology.

PubMed

Czeisler, Catherine; Short, Aaron; Nelson, Tyler; Gygli, Patrick; Ortiz, Cristina; Catacutan, Fay Patsy; Stocker, Ben; Cronin, James; Lannutti, John; Winter, Jessica; Otero, José Javier

2016-12-01

We sought to determine the contribution of scaffold topography to the migration and morphology of neural stem cells by mimicking anatomical features of scaffolds found in vivo. We mimicked two types of central nervous system scaffolds encountered by neural stem cells during development in vitro by constructing different diameter electrospun polycaprolactone (PCL) fiber mats, a substrate that we have shown to be topographically similar to brain scaffolds. We compared the effects of large fibers (made to mimic blood vessel topography) with those of small-diameter fibers (made to mimic radial glial process topography) on the migration and differentiation of neural stem cells. Neural stem cells showed differential migratory and morphological reactions with laminin in different topographical contexts. We demonstrate, for the first time, that neural stem cell biological responses to laminin are dependent on topographical context. Large-fiber topography without laminin prevented cell migration, which was partially reversed by treatment with rock inhibitor. Cell morphology complexity assayed by fractal dimension was inhibited in nocodazole- and cytochalasin-D-treated neural precursor cells in large-fiber topography, but was not changed in small-fiber topography with these inhibitors. These data indicate that cell morphology has different requirements on cytoskeletal proteins dependent on the topographical environment encountered by the cell. We propose that the physical structure of distinct scaffolds induces unique signaling cascades that regulate migration and morphology in embryonic neural precursor cells. J. Comp. Neurol. 524:3485-3502, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Low-intensity vibrations normalize adipogenesis-induced morphological and molecular changes of adult mesenchymal stem cells.

PubMed

Baskan, Oznur; Mese, Gulistan; Ozcivici, Engin

2017-02-01

Bone marrow mesenchymal stem cells that are committed to adipogenesis were exposed daily to high-frequency low-intensity mechanical vibrations to understand molecular, morphological and ultrastructural adaptations to mechanical signals during adipogenesis. D1-ORL-UVA mouse bone marrow mesenchymal stem cells were cultured with either growth or adipogenic medium for 1 week. Low-intensity vibration signals (15 min/day, 90 Hz, 0.1 g) were applied to one group of adipogenic cells, while the other adipogenic group served as a sham control. Cellular viability, lipid accumulation, ultrastructure and morphology were determined with MTT, Oil-Red-O staining, phalloidin staining and atomic force microscopy. Semiquantitative reverse transcription polymerase chain reaction showed expression profile of the genes responsible for adipogenesis and ultrastructure of cells. Low-intensity vibration signals increased viability of the cells in adipogenic culture that was reduced significantly compared to quiescent controls. Low-intensity vibration signals also normalized the effects of adipogenic condition on cell morphology, including area, perimeter, circularization and actin cytoskeleton. Furthermore, low-intensity vibration signals reduced the expression of some adipogenic markers significantly. Mesenchymal stem cells are sensitive and responsive to mechanical loads, but debilitating conditions such as aging or obesity may steer mesenchymal stem cells toward adipogenesis. Here, daily application of low-intensity vibration signals partially neutralized the effects of adipogenic induction on mesenchymal stem cells, suggesting that these signals may provide an alternative and/or complementary option to reduce fat deposition.

Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

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

Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg; Zhu Congju; Wong Yinling

Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival,more » {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G{sub 2}/M arrest, and DNA DSBs, compared with nonstem glioma cells. Gefitinib differentially enhances radiosensitivity of stem-like gliomaspheres by reducing EGFR-Akt activation and DNA-PKcs expression, accompanied by enhanced irradiation-induced DNA DSBs and inhibition of DSB repair.« less

Gefitinib radiosensitizes stem-like glioma cells: inhibition of epidermal growth factor receptor-Akt-DNA-PK signaling, accompanied by inhibition of DNA double-strand break repair.

PubMed

Kang, Khong Bee; Zhu, Congju; Wong, Yin Ling; Gao, Qiuhan; Ty, Albert; Wong, Meng Cheong

2012-05-01

We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H(2)AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H(2)AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G(2)/M arrest and increased γ-H(2)AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H(2)AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G(2)/M arrest, and DNA DSBs, compared with nonstem glioma cells. Gefitinib differentially enhances radiosensitivity of stem-like gliomaspheres by reducing EGFR-Akt activation and DNA-PKcs expression, accompanied by enhanced irradiation-induced DNA DSBs and inhibition of DSB repair. Copyright © 2012 Elsevier Inc. All rights reserved.

AGILE: Autonomous Global Integrated Language Exploitation

DTIC Science & Technology

2009-12-01

combination, including METEOR-based alignment (with stemming and WordNet synonym matching) and GIZA ++ based alignment. So far, we have not seen any...parse trees and a detailed analysis of how function words operate in translation. This program lets us fix alignment errors that systems like GIZA ...correlates better with Pyramid than with Responsiveness scoring (i.e., it is a more precise, careful, measure) • BE generally outperforms ROUGE

"Saviour siblings".

PubMed

Spriggs, M; Savulescu, J

2002-10-01

The Victorian Infertility Treatment Authority has given permission to allow tissue typing in combination with preimplantation genetic diagnosis. This is a new application of IVF. Not only will it allow parents to select an embryo free from serious genetic disease it will allow them to simultaneously select for a match so that the umbilical cord blood of the resulting baby can provide stem cells to treat an existing sibling who has a disease.

Debunking Technical Competency as the Sole Source of Innovation

DTIC Science & Technology

2015-01-01

51 Sustaining vs. Disruptive Technologies Advocates for increasing the number of STEM-credentialed graduates often link U.S. innovation to economic...successful companies are led by talented managers who focus on developing sustaining technologies rather than on what he calls disruptive technologies . Sustaining...simpler, smaller, and frequently more convenient to use.53 Disruptive technologies will eventually overtake or match the performance of the

The Effects of the 1999 Turkish Earthquake on Young Children: Analyzing Traumatized Children's Completion of Short Stories

ERIC Educational Resources Information Center

Oncu, Elif Celebi; Wise, Aysegul Metindogan

2010-01-01

The purpose of this exploratory study was to determine whether projective techniques could identify long-term consequences among children stemming from exposure to a traumatic event. The first group of children (n = 53; 26 female, 27 male) experienced 2 major earthquakes at age 7, 3 months apart, in Turkey, while a similarly matched control group…

Matching motivation enhancement treatment to client motivation: re-examining the Project MATCH motivation matching hypothesis.

PubMed

Witkiewitz, Katie; Hartzler, Bryan; Donovan, Dennis

2010-08-01

The current study was designed to re-examine the motivation matching hypothesis from Project MATCH using growth mixture modeling, an analytical technique that models variation in individual drinking patterns. Secondary data analyses of data from Project MATCH (n = 1726), a large multi-site alcoholism treatment-matching study. Percentage of drinking days was the primary outcome measure, assessed from 1 month to 12 months following treatment. Treatment assignment, alcohol dependence symptoms and baseline percentage of drinking days were included as covariates. The results provided support for the motivation matching hypothesis in the out-patient sample and among females in the aftercare sample: the majority of individuals with lower baseline motivation had better outcomes if assigned to motivation enhancement treatment (MET) compared to those assigned to cognitive behavioral treatment (CBT). In the aftercare sample there was a moderating effect of gender and alcohol dependence severity, whereby males with lower baseline motivation and greater alcohol dependence drank more frequently if assigned to MET compared to those assigned to CBT. Results from the current study lend partial support to the motivation-matching hypothesis and also demonstrated the importance of moderating influences on treatment matching effectiveness. Based upon these findings, individuals with low baseline motivation in out-patient settings and males with low levels of alcohol dependence or females in aftercare settings may benefit more from motivational enhancement techniques than from cognitive-behavioral techniques.

In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.

PubMed

Carter-Arnold, J L; Neilsen, N L; Amelse, L L; Odoi, A; Dhar, M S

2014-09-01

Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. Descriptive study of stem cell characteristics. Equine BMMSCs from 6 horses were cultured in vitro and evaluated for viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of-differentiation markers and gene expression. Equine BMMSCs from all 6 donors demonstrated fibroblastic, cellular morphology, adherence to plastic and expression of cluster-of-differentiation markers. They varied in their rate of proliferation and trilineage differentiation. The equine BMMSCs of one of 6 donors demonstrated a higher rate of proliferation, enhanced ability for cell passaging and a more robust in vitro differentiation. Comparatively, equine BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of osteogenic and chondrogenic differentiation. The results of this study confirm that donor-to-donor variation in equine BMMSCs exists and this variation can be documented using in vitro assays. Subjective assessment suggests that the rate of proliferation tends to correlate with differentiation potential. © 2013 EVJ Ltd.

Donor mesenchymal stem cells home to maternal wounds after transamniotic stem cell therapy (TRASCET) in a rodent model.

PubMed

Graham, Christopher D; Shieh, Hester F; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

2017-06-01

Transamniotic stem cell therapy (TRASCET) with amniotic fluid-derived MSCs (afMSCs) has emerged experimentally as a practical treatment strategy for congenital anomalies. In this study, we sought to determine whether afMSCs migrate to the mother following TRASCET. Pregnant rat dams were divided into three groups. Two groups received volume-matched injections into all amniotic cavities of either a suspension of afMSCs labeled with a luciferase reporter gene or the luciferase protein alone. In a third group, a suspension of labeled cells was aliquoted onto the serosal surface of the uterus. Maternal samples from the laparotomy scar (fascia and skin separately), bone marrow, and peripheral blood were procured, along with placenta and umbilical cord. Specimens were screened for luminescence via microplate luminometry. Luminescence was detected in 60% (9/15) of the fascial scars from the group receiving intraamniotic injection of afMSCs, but in none of the other groups (P<0.001). There was a direct correlation between the presence of donor cells in the placenta and their presence in maternal fascia (Wald test=10.2; P=0.001). Amniotic mesenchymal stem cells migrate to maternal sites of injury after intraamniotic injection. Maternal homing of donor cells must be considered in the setting of transamniotic stem cell therapy. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

Day-night variations in malate concentration, osmotic pressure, and hydrostatic pressure in Cereus validus

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

Luettge, U.; Nobel, P.S.

1984-07-01

Malate concentration and stem osmotic pressure concomitantly increase during nighttime CO/sub 2/ fixation and then decrease during the daytime in the obligate Crassulacean acid metabolism (CAM) plant, Cereus validus (Cactaceae). Changes in malate osmotic pressure calculated using the Van't Hoff relation match the changes in stem osmotic pressure, indicating that changes in malate level affected the water relations of the succulent stems. In contrast to stem osmotic pressure, stem water potential showed little day-night changes, suggesting that changes in cellular hydrostatic pressure occurred. This was corroborated by direct measurements of hydrostatic pressure using the Juelich pressure probe where a smallmore » oil-filled micropipette is inserted directly into chlorenchyma cells, which indicated a 4-fold increase in hydrostatic pressure from dusk to dawn. A transient increase of hydrostatic pressure at the beginning of the dark period was correlated with a short period of stomatal closing between afternoon and nighttime CO/sub 2/ fixation, suggesting that the rather complex hydrostatic pressure patterns could be explained by an interplay between the effects of transpiration and malate levels. A second CAM plant, Agave deserti, showed similar day-night changes in hydrostatic pressure in its succulent leaves. It is concluded that, in addition to the inverted stomatal rhythm, the oscillations of malate markedly affect osmotic pressures and hence water relations of CAM plants. 13 references, 4 figures.« less

Expansion on Stromal Cells Preserves the Undifferentiated State of Human Hematopoietic Stem Cells Despite Compromised Reconstitution Ability

PubMed Central

Magnusson, Mattias; Sierra, Maria I.; Sasidharan, Rajkumar; Prashad, Sacha L.; Romero, Melissa; Saarikoski, Pamela; Van Handel, Ben; Huang, Andy; Li, Xinmin; Mikkola, Hanna K. A.

2013-01-01

Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38−CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38−CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC. PMID:23342037

Identification of Proteins Modulated in the Date Palm Stem Infested with Red Palm Weevil (Rhynchophorus ferrugineus Oliv.) Using Two Dimensional Differential Gel Electrophoresis and Mass Spectrometry

PubMed Central

Rasool, Khawaja Ghulam; Khan, Muhammad Altaf; Aldawood, Abdulrahman Saad; Tufail, Muhammad; Mukhtar, Muhammad; Takeda, Makio

2015-01-01

A state of the art proteomic methodology using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI TOF) has been employed to characterize peptides modulated in the date palm stem subsequent to infestation with red palm weevil (RPW). Our analyses revealed 32 differentially expressed peptides associated with RPW infestation in date palm stem. To identify RPW infestation associated peptides (I), artificially wounded plants (W) were used as additional control beside uninfested plants, a conventional control (C). A constant unique pattern of differential expression in infested (I), wounded (W) stem samples compared to control (C) was observed. The upregulated proteins showed relative fold intensity in order of I > W and downregulated spots trend as W > I, a quite interesting pattern. This study also reveals that artificially wounding of date palm stem affects almost the same proteins as infestation; however, relative intensity is quite lower than in infested samples both in up and downregulated spots. All 32 differentially expressed spots were subjected to MALDI-TOF analysis for their identification and we were able to match 21 proteins in the already existing databases. Relatively significant modulated expression pattern of a number of peptides in infested plants predicts the possibility of developing a quick and reliable molecular methodology for detecting plants infested with date palm. PMID:26287180

Identification of Proteins Modulated in the Date Palm Stem Infested with Red Palm Weevil (Rhynchophorus ferrugineus Oliv.) Using Two Dimensional Differential Gel Electrophoresis and Mass Spectrometry.

PubMed

Rasool, Khawaja Ghulam; Khan, Muhammad Altaf; Aldawood, Abdulrahman Saad; Tufail, Muhammad; Mukhtar, Muhammad; Takeda, Makio

2015-08-17

A state of the art proteomic methodology using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI TOF) has been employed to characterize peptides modulated in the date palm stem subsequent to infestation with red palm weevil (RPW). Our analyses revealed 32 differentially expressed peptides associated with RPW infestation in date palm stem. To identify RPW infestation associated peptides (I), artificially wounded plants (W) were used as additional control beside uninfested plants, a conventional control (C). A constant unique pattern of differential expression in infested (I), wounded (W) stem samples compared to control (C) was observed. The upregulated proteins showed relative fold intensity in order of I > W and downregulated spots trend as W > I, a quite interesting pattern. This study also reveals that artificially wounding of date palm stem affects almost the same proteins as infestation; however, relative intensity is quite lower than in infested samples both in up and downregulated spots. All 32 differentially expressed spots were subjected to MALDI-TOF analysis for their identification and we were able to match 21 proteins in the already existing databases. Relatively significant modulated expression pattern of a number of peptides in infested plants predicts the possibility of developing a quick and reliable molecular methodology for detecting plants infested with date palm.

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

PubMed

Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

2017-03-01

Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A cross-media content analysis of motivational themes in direct-to-consumer prescription drug advertising.

PubMed

Sumpradit, Nithima; Ascione, Frank J; Bagozzi, Richard P

2004-01-01

Direct-to-consumer (DTC) advertising of prescription drugs is a widely discussed issue in health care. However, little is known about the characteristics of the motivational themes used in this type of advertising. The aim of this study was to investigate the concurrent presentation of motivational themes in DTC print and television advertisements. The content analyses focused on advertisements of 2 targeted drug classes (cyclooxygenase-2 enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in magazines and on television. Targeted print advertisements (for celecoxib, rofecoxib, atorvastatin, pravastatin, and simvastatin) from September to December 2001 and targeted television advertisements (for celecoxib, rofecoxib, and simvastatin) from November 2001 were investigated. The motivational themes were assessed using a theoretical framework based on self-regulatory focus theory and cultural orientation. Self-regulatory focus was examined in terms of goal orientation (promotion vs prevention) and emotional aspects, (e.g., cheerfulness, dejection, quiescence, agitation). The cultural orientation was examined in terms of individualism versus collectivism. The visual-verbal match was categorized as direct if the audio and visual information was semantically redundant, as partial if it was partially related, and as no match at all if it was different or conflicting. Twelve print advertisements in 10 magazines and 4 television advertisements on 4 television networks were examined; the interrater reliability scores from 3 independent, trained judges ranged from 0.93 to 0.99. The score was low (0.57) in the visual-verbal match measurement for television advertisements. Products in the same category appeared to be promoted using different self-regulatory foci. For example, celecoxib and atorvastatin advertisements tended to be promotion oriented, whereas pravastatin advertisements tended to be prevention oriented. Motivational themes were found throughout the print advertisements (e.g., pictures, headlines, main text). Only a few advertisements illustrated factual information about a product in a pictorial format. The cultural orientation of the advertisements was similar across brands, with individualistic appeals being common. On television, visual-verbal matches (either direct or partial matches) were generally found, except in the section where risk information was presented. In this content analysis, prescription drugs in the same class appeared to be promoted using different self-regulatory foci, but individualistic appeals were found more often than collectivistic appeals across brands.

EG-13GENOME-WIDE METHYLATION ANALYSIS IDENTIFIES GENOMIC DNA DEMETHYLATION DURING MALIGNANT PROGRESSION OF GLIOMAS

PubMed Central

Saito, Kuniaki; Mukasa, Akitake; Nagae, Genta; Aihara, Koki; Otani, Ryohei; Takayanagi, Shunsaku; Omata, Mayu; Tanaka, Shota; Shibahara, Junji; Takahashi, Miwako; Momose, Toshimitsu; Shimamura, Teppei; Miyano, Satoru; Narita, Yoshitaka; Ueki, Keisuke; Nishikawa, Ryo; Nagane, Motoo; Aburatani, Hiroyuki; Saito, Nobuhito

2014-01-01

Low-grade gliomas often undergo malignant progression, and these transformations are a leading cause of death in patients with low-grade gliomas. However, the molecular mechanisms underlying malignant tumor progression are still not well understood. Recent evidence indicates that epigenetic deregulation is an important cause of gliomagenesis; therefore, we examined the impact of epigenetic changes during malignant progression of low-grade gliomas. Specifically, we used the Illumina Infinium Human Methylation 450K BeadChip to perform genome-wide DNA methylation analysis of 120 gliomas and four normal brains. This study sample included 25 matched-pairs of initial low-grade gliomas and recurrent tumors (temporal heterogeneity) and 20 of the 25 recurring tumors recurred as malignant progressions, and one matched-pair of newly emerging malignant lesions and pre-existing lesions (spatial heterogeneity). Analyses of methylation profiles demonstrated that most low-grade gliomas in our sample (43/51; 84%) had a CpG island methylator phenotype (G-CIMP). Remarkably, approximately 50% of secondary glioblastomas that had progressed from low-grade tumors with the G-CIMP status exhibited a characteristic partial demethylation of genomic DNA during malignant progression, but other recurrent gliomas showed no apparent change in DNA methylation pattern. Interestingly, we found that most loci that were demethylated during malignant progression were located outside of CpG islands. The information of histone modifications patterns in normal human astrocytes and embryonal stem cells also showed that the ratio of active marks at the site corresponding to DNA demethylated loci in G-CIMP-demethylated tumors was significantly lower; this finding indicated that most demethylated loci in G-CIMP-demethylated tumors were likely transcriptionally inactive. A small number of the genes that were upregulated and had demethylated CpG islands were associated with cell cycle-related pathway. In summary, we demonstrated that characteristic DNA demethylation occurred during malignant progression of a subset of low-grade gliomas. The mechanisms underlying and consequences of such DNA demethylation should be studied further.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

PubMed Central

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Ganglioglioma of brain stem and cervicomedullary junction: A 50years review of literature.

PubMed

Janjua, M Burhan; Ivasyk, Iryna; Pisapia, David J; Souweidane, Mark M

2017-10-01

Gangliogliomas are rare low-grade brain tumors composed of both neoplastic glial and neuronal cell elements. The treatment modalities are relatively different in this location and hence factors affecting outcome are poorly understood. We identified 142 brain stem GG patients across 46 studies. The average age was 11.4years with significant difference b/w males and females under the age of 20 (p=0.001). 100% of tumors in the CMJ while, 72% of type I and 86% of type II tumors demonstrated contrast enhancement. 72% of type I and 86% of type II tumors demonstrated contrast enhancement. All BRAF mutation positive tumors demonstrated contrast enhancement. Medulla and pons was the most favorable location followed by medulla alone, and the CMJ. In all tumors "gross total resection" (GTR, 16%), "subtotal resection" (STR, 48%) or "partial resection" (PR, 36%) was achieved. Most subtypes II and III were partially resected (86% and 66%), while, subtype I underwent STR (66%). Only 55% of the patients were positive for the BRAF V600E mutation. The overall survival dropped from 50% at 24 to 10% at 60months, postoperatively. Through this review, we found that an early diagnosis, location, and with the imaging characteristics are vital part of the preoperative planning. Surgical resection is highly dependent on location in the brain stem with radical resection only limited to the most contrast enhancing portion of these tumors. BRAF V600E mutation status should be considered to allow the possibility of targeted therapy in case of a residual tumor and/or regrowth. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Bone-preserving total hip arthroplasty in avascular necrosis of the hip-a matched-pairs analysis.

PubMed

Merschin, David; Häne, Richard; Tohidnezhad, Mersedeh; Pufe, Thomas; Drescher, Wolf

2018-07-01

Short-stem hip arthroplasty has the potential advantage of femoral bone stock preservation, especially in view of the expected revisions in the often relatively young patients. Despite short-stem hip prosthesis are increasingly used for total hip arthroplasty, there are no sufficient mid- and long-term results especially for patients with avascular femoral head osteonecrosis. The present study investigates mid-term functional results as well as the revision rate following implantation of a short-stem prosthesis. In the period 06/2005 until 12/2013, a total of 351 short-stem hip prostheses were implanted. The study included 331 complete data sets. A retrospective analysis was performed using the Oxford Hip Score. All revisions were registered. In a total of 331 prostheses, the Oxford Hip Score was "excellent" in 66.2%, "good" in 12.7%, "fair" in 13.0%, and "poor" in 8.2% with a mean follow-up of 57.4 months (SD ± 29.8; range 24-115). In 26 cases, aseptic osteonecrosis of the hip was the indication (7.9%). The Oxford Hip Score was "excellent" in 66.7%, "good" in 0.0%, "fair" in 20.8%, and "poor" in 12.5%. The cumulated five year survival rate was 96.7%. In mid-term observation, the Metha® short-stem prosthesis shows no disadvantage in functional outcome and in survival time compared to a standard hip stem. Providing a correct indication, the Metha® short stem is a valuable option in total hip arthroplasty for younger patients with avascular osteonecrosis of the femoral head. Evaluation has shown no significant differences between aseptic osteonecrosis and other indications.

The anti-apoptotic effect of IGF-1 on tissue resident stem cells is mediated via PI3-kinase dependent secreted frizzled related protein 2 (Sfrp2) release

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

Gehmert, Sebastian; Sadat, Sanga; Song Yaohua

2008-07-11

Previous studies suggest that IGF-1 may be used as an adjuvant to stem cell transfer in order to improve cell engraftment in ischemic tissue. In the current study, we investigated the effect of IGF-1 on serum deprivation and hypoxia induced stem cell apoptosis and the possible mechanisms involved. Exposure of adipose tissue derived stem cells (ASCs) to serum deprivation and hypoxia resulted in significant apoptosis in ASC which is partially prevented by IGF-1. IGF-1's anti-apoptotic effect was abolished in ASCs transfected with Sfrp2 siRNA but not by the control siRNA. Using Western blot analysis, we demonstrated that serum deprivation andmore » hypoxia reduced the expression of nuclear {beta}-catenin, which is reversed by IGF-1. IGF-1's effect on {beta}-catenin expression was abolished by the presence of PI3-kinase inhibitor LY294002 or in ASCs transfected with Sfrp2 siRNA. These results suggest that IGF-1, through the release of the Sfrp2, contributes to cell survival by stabilizing {beta}-catenin.« less

Robust method for TALEN-edited correction of pF508del in patient-specific induced pluripotent stem cells.

PubMed

Camarasa, María Vicenta; Gálvez, Víctor Miguel

2016-02-09

Cystic fibrosis is one of the most frequent inherited rare diseases, caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Apart from symptomatic treatments, therapeutic protocols for curing the disease have not yet been established. The regeneration of genetically corrected, disease-free epithelia in cystic fibrosis patients is envisioned by designing a stem cell/genetic therapy in which patient-derived pluripotent stem cells are genetically corrected, from which target tissues are derived. In this framework, we present an efficient method for seamless correction of pF508del mutation in patient-specific induced pluripotent stem cells by gene edited homologous recombination. Gene edition has been performed by transcription activator-like effector nucleases and a homologous recombination donor vector which contains a PiggyBac transposon-based double selectable marker cassette.This new method has been designed to partially avoid xenobiotics from the culture system, improve cell culture efficiency and genome stability by using a robust culture system method, and optimize timings. Overall, once the pluripotent cells have been amplified for the first nucleofection, the procedure can be completed in 69 days, and can be easily adapted to edit and change any gene of interest.

GI stem cells – new insights into roles in physiology and pathophysiology

PubMed Central

von Furstenberg, Richard J.

2016-01-01

Abstract This overview gives a brief historical summary of key discoveries regarding stem cells of the small intestine. The current concept is that there are two pools of intestinal stem cells (ISCs): an actively cycling pool that is marked by Lgr5, is relatively homogeneous and is responsible for daily turnover of the epithelium; and a slowly cycling or quiescent pool that functions as reserve ISCs. The latter pool appears to be quite heterogeneous and may include partially differentiated epithelial lineages that can reacquire stem cell characteristics following injury to the intestine. Markers and methods of isolation for active and quiescent ISC populations are described as well as the numerous important advances that have been made in approaches to the in vitro culture of ISCs and crypts. Factors regulating ISC biology are briefly summarized and both known and unknown aspects of the ISC niche are discussed. Although most of our current knowledge regarding ISC physiology and pathophysiology has come from studies with mice, recent work with human tissue highlights the potential translational applications arising from this field of research. Many of these topics are further elaborated in the following articles. PMID:27107928

The persistence of women in STEM: A constructivist grounded theory study

NASA Astrophysics Data System (ADS)

Gamm, Ryan

Men and women have reached relative parity in most sectors of the United States workforce. Yet women remain underrepresented in science, technology, engineering, and mathematics (STEM) fields (AAUW, 2010). Underrepresentation persists despite several decades of research, legislation, and intervention focused on gender equality in STEM fields (Clewell, 2002). The underrepresentation or shortage of women in STEM fields is identifiable primarily in degree attainment, in workforce demographics, and in a gender wage gap. Situated in constructivist grounded theory, this study asks how do women in science, technology, engineering, and mathematics (STEM) fields, particularly those in established career positions, persist when encountering personal and institutional barriers, resistance, and hostility? I use an interpretive-constructivist lens to conduct a grounded theory study exploring the experiences of women who persist in STEM fields, their relation to extant literature on this topic, and the connections to K-12 education practices, specifically curriculum. To understand the connections to curriculum I employ Pinar's (2012) method of currere. Pinar (2012) contends currere "provides a strategy for students of curriculum to study the relations between academic knowledge and life history in the interests of self-understanding and social reconstruction" (p.44). This qualitative study explored nine female STEM workers stories of persistence as each respondent works in STEM fields were gender parity has yet to be established. This study presents a substantive theory: As women persist in STEM fields they reframe themselves to be situated in the overlapping intersection of the social processes that correspond to "engagement" and "persistence." This reframing is possible by interpreting one's present day circumstances by independently removing oneself from current circumstances to understand the cumulative effect of both past and present. The findings highlight the importance of early educative experiences and their reinforcement throughout formal education including the STEM pipeline. The findings suggest that how one understands and interprets STEM work, and the compatibility ones' own identity with this work are crucial, reinforcing the some of the diverse body of literature that seeks to understand women's underrepresentation in STEM. Although literature focused on STEM related education, including work examining gender, offers suggestions compatible with the findings of this study, experiences that are match the stories of the respondents appear to be outside of the norm.

Induced Pluripotent Stem Cell–Derived Cardiomyocytes Provide In Vivo Biological Pacemaker Function

PubMed Central

Chauveau, Samuel; Anyukhovsky, Evgeny P.; Ben-Ari, Meital; Naor, Shulamit; Jiang, Ya-Ping; Danilo, Peter; Rahim, Tania; Burke, Stephanie; Qiu, Xiaoliang; Potapova, Irina A.; Doronin, Sergey V.; Brink, Peter R.; Binah, Ofer

2017-01-01

Background— Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model. Methods and Results— Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified. Atrioventricular blocked dogs were immunosuppressed, instrumented with VVI pacemakers, and injected subepicardially into the anterobasal left ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3–2×106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4 to 13 weeks, epinephrine (1 μg kg−1 min−1) was infused, and the heart removed for histological or electrophysiological study. iPSC-CMs largely lost the markers of pluripotency, became positive for cardiac-specific markers. and manifested If-dependent automaticity. Epicardial pacing of the injection site identified matching beats arising from that site by week 1 after implantation. By week 4, 20% of beats were electronically paced, 60% to 80% of beats were matching, and mean and maximal biological pacemaker rates were 45 and 75 beats per minute. Maximum night and day rates of matching beats were 53±6.9 and 69±10.4 beats per minute, respectively, at 4 weeks. Epinephrine increased rate of matching beats from 35±4.3 to 65±4.0 beats per minute. Incubation of embryoid bodies with the vital dye, Dil, revealed the persistence of injected cells at the site of administration. Conclusions— iPSC-CMs can integrate into host myocardium and create a biological pacemaker. Although this is a promising development, rate and rhythm of the iPSC-CMs pacemakers remain to be optimized. PMID:28500172

Assessment of cellular materials generated by co-cultured 'inflamed' and healthy periodontal ligament stem cells from patient-matched groups.

PubMed

Tang, Hao-Ning; Xia, Yu; Xu, Jie; Tian, Bei-Min; Zhang, Xi-Yu; Chen, Fa-Ming

2016-08-01

Recently, stem cells derived from the'inflamed' periodontal ligament (PDL) tissue of periodontally diseased teeth (I-PDLSCs) have been increasingly suggested as a more readily accessible source of cells for regenerative therapies than those derived from healthy PDL tissue (H-PDLSCs). However, substantial evidence indicates that I-PDLSCs exhibit impaired functionalities compared with H-PDLSCs. In this study, patient-matched I-PDLSCs and H-PDLSCs were co-cultured at various ratios. Cellular materials derived from these cultures were investigated regarding their osteogenic potential in vitro and capacity to form new bone following in vivo transplantation. While patient-matched I-PDLSCs and H-PDLSCs could co-exist in co-culture systems, the proportion of I-PDLSCs tended to increase during in vitro incubation. Compared with H-PDLSC monoculture, the presence of I-PDLSCs in the co-cultures appeared to enhance the overall cell proliferation. Although not completely rescued, the osteogenic and regenerative potentials of the cellular materials generated by co-cultured I-PDLSCs and H-PDLSCs were significantly improved compared with those derived from I-PDLSC monocultures. Notably, cells in co-cultures containing either 50% I-PDLSCs plus 50% H-PDLSCs or 25% I-PDLSCs plus 75% H-PDLSCs expressed osteogenesis-related proteins and genes at levels similar to those expressed in H-PDLSC monocultures (P>0.05). Irrespective of the percentage of I-PDLSCs, robust cellular materials were obtained from co-cultures with 50% or more H-PDLSCs, which exhibited equivalent potential to form new bone in vivo compared with sheets generated by H-PDLSC monocultures. These data suggest that the co-culture of I-PDLSCs with patient-matched H-PDLSCs is a practical and effective method for increasing the overall osteogenic and regenerative potentials of resultant cellular materials. Copyright © 2016 Elsevier Inc. All rights reserved.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT.

PubMed

Dufour, Carlo; Veys, Paul; Carraro, Elisa; Bhatnagar, Neha; Pillon, Marta; Wynn, Rob; Gibson, Brenda; Vora, Ajay J; Steward, Colin G; Ewins, Anna M; Hough, Rachael E; de la Fuente, Josu; Velangi, Mark; Amrolia, Persis J; Skinner, Roderick; Bacigalupo, Andrea; Risitano, Antonio M; Socie, Gerard; Peffault de Latour, Regis; Passweg, Jakob; Rovo, Alicia; Tichelli, André; Schrezenmeier, Hubert; Hochsmann, Britta; Bader, Peter; van Biezen, Anja; Aljurf, Mahmoud D; Kulasekararaj, Austin; Marsh, Judith C; Samarasinghe, Sujith

2015-11-01

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Adaptive object tracking via both positive and negative models matching

NASA Astrophysics Data System (ADS)

Li, Shaomei; Gao, Chao; Wang, Yawen

2015-03-01

To improve tracking drift which often occurs in adaptive tracking, an algorithm based on the fusion of tracking and detection is proposed in this paper. Firstly, object tracking is posed as abinary classification problem and is modeled by partial least squares (PLS) analysis. Secondly, tracking object frame by frame via particle filtering. Thirdly, validating the tracking reliability based on both positive and negative models matching. Finally, relocating the object based on SIFT features matching and voting when drift occurs. Object appearance model is updated at the same time. The algorithm can not only sense tracking drift but also relocate the object whenever needed. Experimental results demonstrate that this algorithm outperforms state-of-the-art algorithms on many challenging sequences.

Model-based occluded object recognition using Petri nets

NASA Astrophysics Data System (ADS)

Zhou, Chuan; Hura, Gurdeep S.

1998-09-01

This paper discusses the use of Petri nets to model the process of the object matching between an image and a model under different 2D geometric transformations. This transformation finds its applications in sensor-based robot control, flexible manufacturing system and industrial inspection, etc. A description approach for object structure is presented by its topological structure relation called Point-Line Relation Structure (PLRS). It has been shown how Petri nets can be used to model the matching process, and an optimal or near optimal matching can be obtained by tracking the reachability graph of the net. The experiment result shows that object can be successfully identified and located under 2D transformation such as translations, rotations, scale changes and distortions due to object occluded partially.

ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia

PubMed Central

Weisberg, Stuart P.; Smith-Raska, Matthew R.; Esquilin, Jose M.; Zhang, Ji; Arenzana, Teresita L.; Lau, Colleen M.; Churchill, Michael; Pan, Haiyan; Klinakis, Apostolos; Dixon, Jack E.; Mirny, Leonid A.; Mukherjee, Siddhartha; Reizis, Boris

2014-01-01

Summary Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem cell-related genetic regulator. PMID:24485662

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

PubMed Central

Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

2014-01-01

Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

Epigenomic Analysis of Multi-lineage Differentiation of Human Embryonic Stem Cells

PubMed Central

Xie, Wei; Schultz, Matthew D.; Lister, Ryan; Hou, Zhonggang; Rajagopal, Nisha; Ray, Pradipta; Whitaker, John W.; Tian, Shulan; Hawkins, R. David; Leung, Danny; Yang, Hongbo; Wang, Tao; Lee, Ah Young; Swanson, Scott A.; Zhang, Jiuchun; Zhu, Yun; Kim, Audrey; Nery, Joseph R.; Urich, Mark A.; Kuan, Samantha; Yen, Chia-an; Klugman, Sarit; Yu, Pengzhi; Suknuntha, Kran; Propson, Nicholas E.; Chen, Huaming; Edsall, Lee E.; Wagner, Ulrich; Li, Yan; Ye, Zhen; Kulkarni, Ashwinikumar; Xuan, Zhenyu; Chung, Wen-Yu; Chi, Neil C.; Antosiewicz-Bourget, Jessica E.; Slukvin, Igor; Stewart, Ron; Zhang, Michael Q.; Wang, Wei; Thomson, James A.; Ecker, Joseph R.; Ren, Bing

2013-01-01

SUMMARY Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells, and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in non-expressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation. PMID:23664764

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Long Term Liver Engraftment of Functional Hepatocytes Obtained from Germline Cell-Derived Pluripotent Stem Cells

PubMed Central

Fagoonee, Sharmila; Famulari, Elvira Smeralda; Silengo, Lorenzo; Tolosano, Emanuela; Altruda, Fiorella

2015-01-01

One of the major hurdles in liver gene and cell therapy is availability of ex vivo-expanded hepatocytes. Pluripotent stem cells are an attractive alternative. Here, we show that hepatocyte precursors can be isolated from male germline cell-derived pluripotent stem cells (GPSCs) using the hepatoblast marker, Liv2, and induced to differentiate into hepatocytes in vitro. These cells expressed hepatic-specific genes and were functional as demonstrated by their ability to secrete albumin and produce urea. When transplanted in the liver parenchyma of partially hepatectomised mice, Liv2-sorted cells showed regional and heterogeneous engraftment in the injected lobe. Moreover, approximately 50% of Y chromosome-positive, GPSC-derived cells were found in the female livers, in the region of engraftment, even one month after cell injection. This is the first study showing that Liv2-sorted GPSCs-derived hepatocytes can undergo long lasting engraftment in the mouse liver. Thus, GPSCs might offer promise for regenerative medicine. PMID:26323094

Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells.

PubMed

Boddy, Sarah L; Chen, Wei; Romero-Guevara, Ricardo; Kottam, Lucksy; Bellantuono, Illaria; Rivolta, Marcelo N

2012-11-01

Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce inner ear hair cell-like cells. An equivalent source from humans is highly desirable, given their potential application in patient-specific regenerative therapies for deafness. In this study, we explored the ability of human MSCs (hMSCs) to differentiate into otic lineages. hMSCs were exposed to culture media conditioned by human fetal auditory stem cells. Conditioned media induced the expression of otic progenitor markers PAX8, PAX2, GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3 (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH. Inhibition of WNT signaling prevented differentiation into otic progenitors, while WNT activation partially phenocopied results seen with the conditioned media. This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.

Evaluation of Corneal Neovascularization Using Optical Coherence Tomography Angiography in Patients With Limbal Stem Cell Deficiency.

PubMed

Oie, Yoshinori; Nishida, Kohji

2017-11-01

Detection of the exact area of corneal neovascularization using slit-lamp photography is often difficult. Thus, we evaluated corneal neovascularization in patients with limbal stem cell deficiency using optical coherence tomography angiography (OCTA). Five patients with 5 eyes showing partial or total limbal stem cell deficiency were enrolled. Three eyes had severe corneal scarring. Five 6- × 6-mm images (frontal, upper, lower, nasal, and temporal) were obtained by OCTA. Slit-lamp photography was performed for all patients on the same day. OCTA has 2 advantages over slit-lamp photography for clear demonstration of corneal neovascularization. First, OCTA can show neovascularization in cases with severe corneal opacification. Second, OCTA can detect not only large vessels but also small vessels that cannot be seen by slit-lamp photography. OCTA is a powerful tool for objective evaluation of vascularization in the anterior and posterior segments of the eye. We have demonstrated that OCTA can visualize corneal neovascularization in patients with corneal diseases more clearly than slit-lamp photography.

Using the Optical Mouse Sensor as a Two-Euro Counterfeit Coin Detector

PubMed Central

Tresanchez, Marcel; Pallejà, Tomàs; Teixidó, Mercè; Palacín, Jordi

2009-01-01

In this paper, the sensor of an optical mouse is presented as a counterfeit coin detector applied to the two-Euro case. The detection process is based on the short distance image acquisition capabilities of the optical mouse sensor where partial images of the coin under analysis are compared with some partial reference coin images for matching. Results show that, using only the vision sense, the counterfeit acceptance and rejection rates are very similar to those of a trained user and better than those of an untrained user. PMID:22399987

Analytical study on the thermal performance of a partially wet constructal T-shaped fin

NASA Astrophysics Data System (ADS)

Hazarika, Saheera Azmi; Zeeshan, Mohd; Bhanja, Dipankar; Nath, Sujit

2017-07-01

The present paper addresses the thermal analysis of a T-shaped fin under partially wet condition by adopting a cubic variation of the humidity ratio of saturated air with the corresponding fin surface temperature. The point separating the dry and wet parts may lie either in the flange or stem part of the fin and so, two different cases having different governing equations and boundary conditions are analyzed in this paper. Since the governing equations are highly non-linear, they are solved by using an analytical technique called the Differential Transform Method and subsequently, the dry fin length, temperature distribution and fin performances are evaluated and analyzed for a wide range of the various psychometric, geometric and thermo-physical parameters. Finally, it can be highlighted that relative humidity has a pronounced effect on the performance parameters when the fin surface is partially wet whereas this effect is marginally small for fully wet surface.

Children's Sensitivity to Different Modes of Colour Use in Art.

ERIC Educational Resources Information Center

O'Hare, D.; Cook, Deborah

1983-01-01

Reports on age differences found in children's (1) ability to execute appropriate differences in the uses of color while completing partially drawn scenes; and (2) sensitivity to differences between heraldic, gradation, harmonic, and pure use of color in a matching task. (GC)