Combined Error Correction Techniques for Quantum Computing Architectures

Proposals for quantum computing devices are many and varied. They each have unique noise processes that make none of them fully reliable at this time. There are several error correction/avoidance techniques which are valuable for reducing or eliminating errors, but not one, alone, will serve as a panacea. One must therefore take advantage of the strength of each of these techniques so that we may extend the coherence times of the quantum systems and create more reliable computing devices. To this end we give a general strategy for using dynamical decoupling operations on encoded subspaces. These encodings may be of any form; of particular importance are decoherence-free subspaces and quantum error correction codes. We then give means for empirically determining an appropriate set of dynamical decoupling operations for a given experiment. Using these techniques, we then propose a comprehensive encoding solution to many of the problems of quantum computing proposals which use exchange-type interactions. This uses a decoherence-free subspace and an efficient set of dynamical decoupling operations. It also addresses the problems of controllability in solid state quantum dot devices.Comment: Contribution to Proceedings of the 2002 Physics of Quantum Electronics Conference", to be published in J. Mod. Optics. This paper provides a summary and review of quant-ph/0205156 and quant-ph/0112054, and some new result

Recent Patents Pertaining to Immune Modulation and Musculoskeletal Regeneration with Wharton's Jelly Cells

This is the author's accepted manuscript. Made available by the permission of the publisher.Umbilical cord mesenchymal stromal cells (UCMSCs) are isolated from Wharton's jelly in the umbilical cord at birth, and offer advantages over adult mesenchymal stromal cells (MSCs) such as highly efficient isolation, faster proliferation in vitro, a broader differentiation potential, and non-invasive harvesting procedure. Their expansion and differentiation potential renders them a promising cell source for tissue engineering and clinical applications. This review discusses recent updates on the differentiation strategies for musculoskeletal tissue engineering including cartilage, bone, and muscle. In addition to tissue engineering applications, UCMSCs can be utilized to support hematopoiesis and modulate immune response. We review the patents relevant to the application of MSCs including UCMSCs in hematopoiesis and immune modulation. Finally, the current hurdles in the clinical translation of UCMSCs are discussed. During clinical translation, it is critical to develop large-scale manufacturing of UCMSCs as well as the composition of expansion and differentiation media. Four clinical trials to date have examined the safety and efficacy of UCMSCs. Once public banking of UCMSCs is available to supply matched allogeneic units and once UCMSC manufacturing is standardized, we anticipate that UCMSCs will be more widely used in clinical trials

Diverse Expression Patterns and Tumorigenic Role of Neurotensin Signaling Components in Colorectal Cancer Cells

Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC. In this study, we investigated the expression profiles and cellular functions of the NTSRs, especially NTSR1, in CRC cells. We showed that expression levels for NTS and NTSR1 varied, that NTSR2 expression was not detectable and that NTSR3 was consistently expressed in all CRC cell lines examined. Treatment with the demethylating agent, 5-aza-2\u27-deoxycytidine, augmented levels of NTSR1/2 in Caco2 and DLD1 cells, which have little or no transcripts for NTSR1/2 suggesting that DNA methylation suppresses NTSR1/2 expression. In addition, we demonstrated that knockdown of NTSR1 decreased cell growth and migration in HCT116 and HT29 cells. Finally, we showed that treatment with SR48692, an antagonist of NTSR1, also inhibited cell proliferation and migration in the CRC cells. Our findings identify promoter methylation as an important process regulating the differential expression or silencing of NTSR1/2 in CRC cells. Moreover, inhibition of NTSR1 repressed tumorigenic effects in CRC cells, suggesting that NTSR1 may be used as a therapeutic target for CRC

Wharton’s jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report

The therapeutic effect of mesenchymal stromal cells (MSCs) following myocardial infarction (MI) is small. This may be due to differences in cellular sources and donor age, route of administration, in vitro cellular manipulations and the short time course of follow up in many animal studies. Here, we compared MSCs from two different sources (adult bone marrow or Wharton’s jelly from umbilical cord) for their long-term therapeutic effect following MI in a rat model to evaluate the effect of donor age. MSCs (or control infusions) were given intravenously 24-48 hr after myocardial ischemia (MI) induced by coronary artery ligation. Cardiac function was assessed by ultrasound at time points starting from before MSC infusion through 68 weeks after MI. A significant improvement in ejection fraction was seen in animals that received MSCs in time points 25 to 31 wks after treatment (p <0.01). These results support previous work that show that MSCs can cause improvement in cardiac function and extend that work by showing that the beneficial effects are durable. To investigate MSCs’ cardiac differentiation potential, Wharton’s jelly MSCs were co-cultured with fetal or adult bone-derived marrow MSCs. When Wharton’s jelly MSCs were co-cultured with fetal MSCs, and not with adult MSCs, myotube structures were observed in two-three days and spontaneous contractions (beating) cells were observed in fiveseven days. The beating structures formed a functional syncytium indicated by coordinated contractions (beating) of independent nodes. Taken together, these results suggest that MSCs given 24-48 hr after MI have a significant and durable beneficial effect more than 25 weeks after MI and that MSC treatment can home to damaged tissue and improve heart function after intravenous infusion 24-48 hrs after MI, and that WJCs may be a useful source for off-the-shelf cellular therapy for MI

Manufacturing Cells for Clinical Use

Citation: Weiss, M. L., Rao, M. S., Deans, R., & Czermak, P. (2016). Manufacturing Cells for Clinical Use. Stem Cells International, 5. doi:10.1155/2016/1750697The growth in the number of registered clinical trials indicates that there is a need for cells for many types of cell therapy. Figure 1, which is reprinted from the excellent blog maintained by Alexi Bersenev, shows that the cell type used in most clinical trials worldwide is the mesenchymal stromal cell (MSC). The MSC type requires in vitro expansion to reach a clinical dose and thus there is a desire to optimize and standardize processes and procedures for MSC manufacture specifically for clinical use

Nuclear Factor of Activated T-Cells 5 Increases Intestinal Goblet Cell Differentiation Through an mTOR/Notch Signaling Pathway

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis that is regulated by multiple signaling pathways. Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5) is involved in the regulation of intestinal enterocyte differentiation. Here we show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling, increased mTORC1 repressor regulated in development and DNA damage response 1 (REDD1) protein expression and inhibited mTOR signaling; these alterations were attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression and protein expression. Consistently, overexpression of NFAT5 increased REDD1 expression. In addition, knockdown of REDD1 activated mTOR and Notch signaling, whereas treatment with mTOR inhibitor rapamycin repressed Notch signaling and increased the expression of the goblet cell differentiation marker mucin 2 (MUC2). Moreover, knockdown of NFAT5 activated Notch signaling and decreased MUC2 expression, while overexpression of NFAT5 inhibited Notch signaling and increased MUC2 expression. Our results demonstrate a role for NFAT5 in the regulation of mTOR signaling in intestinal cells. Importantly, these data suggest that NFAT5 participates in the regulation of intestinal homeostasis via the suppression of mTORC1/Notch signaling pathway

Wharton’s jelly-derived mesenchymal stromal cells as a promising cellular therapeutic strategy for the management of graft-versus-host disease

Citation: McGuirk, J. P., Robert Smith, J., Divine, C. L., Zuniga, M., & Weiss, M. L. (2015). Wharton’s jelly-derived mesenchymal stromal cells as a promising cellular therapeutic strategy for the management of graft-versus-host disease. Pharmaceuticals, 8(2), 196-220. doi:10.3390/ph8020196Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines) to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD. © 2015 by the authors; licensee MDPI, Basel, Switzerland

A Comparison of Human Bone Marrow Derived Mesenchymal Stem Cells and Human Umbilical Cord-Derived Mesenchymal Stromal Cells for Cartilage Tissue Engineering

Abstract Bone marrow derived mesenchymal stem cells (BMSCs) have long been considered the criterion standard for stem cell sources in musculoskeletal tissue engineering. The true test of a stem cell source is a side-by-side comparison with BMSCs. Human umbilical cord derived mesenchymal stromal cells (hUCMSCs), one such candidate with high potential, are a fetus-derived stem cell source collected from discarded tissue (Wharton's jelly) after birth. Compared with human BMSCs (hBMSCs), hUCMSCs have the advantages of abundant supply, painless collection, no donor site morbidity, and faster and longer self-renewal in vitro. In this 6-week study, a chondrogenic comparison was conducted of hBMSCs and hUCMSCs in a three-dimensional (3D) scaffold for the first time. Cells were seeded on polyglycolic acid (PGA) scaffolds at 25M cells/mL and then cultured in identical conditions. Cell proliferation, biosynthesis, and chondrogenic differentiation were assessed at weeks 0, 3, and 6 after seeding. At weeks 3 and 6, hUCMSCs produced more glycosaminoglycans than hBMSCs. At week 6, the hUCMSC group had three times as much collagen as the hBMSC group. Immunohistochemistry revealed the presence of collagen types I and II and aggrecan in both groups, but type II collagen staining was more intense for hBMSCs than hUCMSCs. At week 6, the quantitative reverse transcriptase polymerase chain reaction (RT-PCR) revealed less type I collagen messenger RNA (mRNA) with both cell types, and more type II collagen mRNA with hBMSCs, than at week 3. Therefore, it was concluded that hUCMSCs may be a desirable option for use as a mesenchymal cell source for fibrocartilage tissue engineering, based on abundant type I collagen and aggrecan production of hUCMSCs in a 3D matrix, although further investigation of signals that best promote type II collagen production of hUCMSCs is warranted for hyaline cartilage engineering.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78138/1/ten.tea.2008.0393.pd