Genetics Home Reference: spastic paraplegia type 15

MedlinePlus

... This protein is important in a process called autophagy, in which worn-out cell parts and unneeded ... As a result, functional autophagosomes are not produced, autophagy cannot occur, and recycling of materials within cells ...

Patent prosecution strategies for stem cell related applications.

PubMed

Kumar, Rajeev; Yeh, Jenny J; Fernandez, Dennis; Hansen, Nels

2007-09-01

Stem cell research and the intellectual property derived from it, because of its potential to completely transform health care, demand an especially high level of consideration from business and patent prosecution perspectives. As with other revolutionary technologies, ordinary risks are amplified (e.g., litigation), and ordinarily irrelevant considerations may become important (e.g., heightened level of both domestic and foreign legislative risk). In the first part of this article, general strategies for patent prosecutors such as several prosecution considerations and methods for accelerating patent prosecution process are presented. In the second part, patent prosecution challenges of stem cell-related patents and possible solutions are discussed. In the final part, ethical and public policy issues particular to stem cell-related and other biotechnological inventions are summarized.

Do not let death do us part: 'find-me' signals in communication between dying cells and the phagocytes.

PubMed

Medina, C B; Ravichandran, K S

2016-06-01

The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment.

Do not let death do us part: ‘find-me' signals in communication between dying cells and the phagocytes

PubMed Central

Medina, C B; Ravichandran, K S

2016-01-01

The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of ‘find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment. PMID:26891690

Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

PubMed

Husari, Ayman; Hülter-Hassler, Diana; Steinberg, Thorsten; Schulz, Simon Daniel; Tomakidi, Pascal

2018-01-01

Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment. Concerning adherens junctions (AJs), both EPI and FIB showed membrane-bound β-catenin, but exhibited differences for E-cadherin and zyxin. While EPI revealed E-cadherin/β-catenin membrane co-localization, which in parts also applied for zyxin, FIB membranes were devoid of E-cadherin and exhibited marginal zyxin expression. Fetal calf serum (FCS) administration in starved cells promoted proliferation in both keratinocyte phenotypes, whereat EPI and FIB yielded a strikingly modified FCS sensitivity on the temporal scale. Impedance measurement-based cell index detection yielded proliferation stimulation occurring much earlier in FIB (<20h) compared to EPI (>45h). Nuclear preference of the proliferation-associated YAP co-transcription factor in FIB was FCS independent, while it required FCS in EPI. Taken together, the lack of membrane-inherent E-cadherin/β-catenin co-localization together with low zyxin - reveals perturbation of AJ integrity in FIB. Regarding cell behavior, perturbed AJs in FIB correlate with temporal proliferation sensitivity towards FCS. CYF of 5.6 strongly suggests involvement of chromatin-bound YAP in FIB's proliferation temperosensitivity. These molecular differences detected for EPI and FIB are part of the underlying cell transformation process of alcohol-induced oral carcinogenesis, and indicate FIB being in a more advanced transformation stage. Copyright © 2017 Elsevier B.V. All rights reserved.

Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency.

PubMed

Zueva, Lidia; Golubeva, Tatiana; Korneeva, Elena; Makarov, Vladimir; Khmelinskii, Igor; Inyushin, Mikhail

2016-04-01

Specialized intermediate filaments (IFs) have critical importance for the clearness and uncommon transparency of vertebrate lens fiber cells, although the physical mechanisms involved are poorly understood. Recently, an unusual low-scattering light transport was also described in retinal Müller cells. Exploring the function of IFs in Müller cells, we have studied the morphology and distribution pattern of IFs and other cytoskeletal filaments inside the Müller cell main processes in the foveolar part of the avian (pied flycatcher) retina. We found that some IFs surrounded by globular nanoparticles (that we suggest are crystallines) are present in almost every part of the Müller cells that span the retina, including the microvilli. Unlike IFs implicated in the mechanical architecture of the cell, these IFs are not connected to any specific cellular membranes. Instead, they are organized into bundles, passing inside the cell from the endfeet to the photoreceptor, following the geometry of the processes, and repeatedly circumventing numerous obstacles. We believe that the presently reported data effectively confirm that the model of nanooptical channels built of the IFs may provide a viable explanation of Müller cell transparency.

Histomorphometric analysis of collagen architecture of auricular keloids in an Asian population.

PubMed

Chong, Yosep; Park, Tae Hwan; Seo, Sang won; Chang, Choong Hyun

2015-03-01

Keloids are a pathologic condition of the reparative process, which present as excessive scar formation that involves various cells and cytokines. Many studies focusing on the histologic feature of keloids, however, have shown discordant results without consideration of architectural aspect of collagen structure. The purpose of this study was to demonstrate a schematic illustration of collagen architecture of keloids, specifically auricular keloids, and to analyze each part on the histomorphologic and morphometric basis. Thirty-nine surgically excised auricular keloids were retrieved from the file of Kangbuk Samsung Hospital. After exhaustive histomorphologic analysis, 3 distinctive structural parts, keloidal collagen, organizing collagen, and proliferating core collagen, were identified and mapped in every case. Cellularity of fibroblasts, blood vessel density, degree of inflammatory cell infiltration, and mast cells counts using Masson trichrome stain, Van Gieson stain, toluidine blue stain, and immunohistochemical stains for CD31 and smooth muscle actin were analyzed in each part of each case. Morphometric analysis on these parameters using ImageJ software was performed using 3 representative images of each part. Three parts were histomorphologically distinct by shape and array of collagen bundles, fibroblasts cellularity, blood vessel density, degree of inflammatory cells, and mast cell infiltration. Morphometric analysis revealed statistically significant difference between each part in fibroblasts cellularity, blood vessel density, degree of inflammatory cell infiltration, and mast cells count. All parameters were exceedingly high in whorling hypercellular fibrous nodules in proliferating core collagen showing simultaneous changes in other parts. Morphologically and morphometrically, 3 distinctive parts were identified in auricular keloids. Mast cell infiltrations, blood vessel density, and fibroblast cellularity are simultaneously increased or decreased according to these parts. Proliferating core collagen might serve as a proliferating center of keloids and might be a key portion for tumor growth and recurrence.

Process Development of Gallium Nitride Phosphide Core-Shell Nanowire Array Solar Cell

NASA Astrophysics Data System (ADS)

Chuang, Chen

Dilute Nitride GaNP is a promising materials for opto-electronic applications due to its band gap tunability. The efficiency of GaNxP1-x /GaNyP1-y core-shell nanowire solar cell (NWSC) is expected to reach as high as 44% by 1% N and 9% N in the core and shell, respectively. By developing such high efficiency NWSCs on silicon substrate, a further reduction of the cost of solar photovoltaic can be further reduced to 61$/MWh, which is competitive to levelized cost of electricity (LCOE) of fossil fuels. Therefore, a suitable NWSC structure and fabrication process need to be developed to achieve this promising NWSC. This thesis is devoted to the study on the development of fabrication process of GaNxP 1-x/GaNyP1-y core-shell Nanowire solar cell. The thesis is divided into two major parts. In the first parts, previously grown GaP/GaNyP1-y core-shell nanowire samples are used to develop the fabrication process of Gallium Nitride Phosphide nanowire solar cell. The design for nanowire arrays, passivation layer, polymeric filler spacer, transparent col- lecting layer and metal contact are discussed and fabricated. The property of these NWSCs are also characterized to point out the future development of Gal- lium Nitride Phosphide NWSC. In the second part, a nano-hole template made by nanosphere lithography is studied for selective area growth of nanowires to improve the structure of core-shell NWSC. The fabrication process of nano-hole templates and the results are presented. To have a consistent features of nano-hole tem- plate, the Taguchi Method is used to optimize the fabrication process of nano-hole templates.

More Genetic Engineering With Cloned Hemoglobin Genes

NASA Technical Reports Server (NTRS)

Bailey, James E.

1992-01-01

Cells modified to enhance growth and production of proteins. Method for enhancing both growth of micro-organisms in vitro and production of various proteins or metalbolites in these micro-organisms provides for incorporation of selected chromosomal or extrachormosomal deoxyribonucleic acid (DNA) sequences into micro-organisms from other cells or from artificial sources. Incorporated DNA includes parts encoding desired product(s) or characteristic(s) of cells and parts that control expression of productor characteristic-encoding parts in response to variations in environment. Extended method enables increased research into growth of organisms in oxygen-poor environments. Industrial applications found in enhancement of processing steps requiring oxygen in fermentation, enzymatic degradation, treatment of wastes containing toxic chemicals, brewing, and some oxidative chemical reactions.

How dying cells alert the immune system to danger

PubMed Central

Kono, Hajime; Rock, Kenneth L.

2009-01-01

When a cell dies in vivo the event does not go unnoticed. The host has evolved mechanisms to detect the death of cells and rapidly investigate the nature of their demise. If cell death is a result of natural causes, that is, it is part of normal physiological processes, then there is little threat to the organism. In this situation, little else is done other than removing the corpse. However, if cells have died as the consequence of some violence or disease, then both defence and repair mechanisms are mobilized. The importance of this process to host defence and disease pathogenesis has only been appreciated relatively recently. This article will review our current knowledge of these processes. PMID:18340345

Rapid prototype fabrication processes for high-performance thrust cells

NASA Technical Reports Server (NTRS)

Hunt, K.; Chwiedor, T.; Diab, J.; Williams, R.

1994-01-01

The Thrust Cell Technologies Program (Air Force Phillips Laboratory Contract No. F04611-92-C-0050) is currently being performed by Rocketdyne to demonstrate advanced materials and fabrication technologies which can be utilized to produce low-cost, high-performance thrust cells for launch and space transportation rocket engines. Under Phase 2 of the Thrust Cell Technologies Program (TCTP), rapid prototyping and investment casting techniques are being employed to fabricate a 12,000-lbf thrust class combustion chamber for delivery and hot-fire testing at Phillips Lab. The integrated process of investment casting directly from rapid prototype patterns dramatically reduces design-to-delivery cycle time, and greatly enhances design flexibility over conventionally processed cast or machined parts.

Electrochemical process and production of novel complex hydrides

DOEpatents

Zidan, Ragaiy

2013-06-25

A process of using an electrochemical cell to generate aluminum hydride (AlH.sub.3) is provided. The electrolytic cell uses a polar solvent to solubilize NaAlH.sub.4. The resulting electrochemical process results in the formation of AlH.sub.3. The AlH.sub.3 can be recovered and used as a source of hydrogen for the automotive industry. The resulting spent aluminum can be regenerated into NaAlH.sub.4 as part of a closed loop process of AlH.sub.3 generation.

Improvements in Cz silicon PV module manufacturing

NASA Astrophysics Data System (ADS)

King, Richard R.; Mitchell, Kim W.; Jester, Theresa L.

1997-02-01

Work focused on reducing the cost per watt of Cz Si photovoltaic modules under Phase I of Siemens Solar Industries' DOE/NREL PVMaT 4A subcontract is described. Module cost components are analyzed and solutions to high-cost items are discussed in terms of specific module designs. The approaches of using larger cells and modules to reduce per-part processing cost, and of minimizing yield loss are particularly leveraging. Yield components for various parts of the fabrication process and various types of defects are shown, and measurements of the force required to break wafers throughout the cell fabrication sequence are given. The most significant type of yield loss is mechanical breakage. The implementation of statistical process control on key manufacturing processes at Siemens Solar Industries is described. Module configurations prototyped during Phase I of this project and scheduled to begin production in Phase II have a projected cost per watt reduction of 19%.

Intestinal transfer of choline in rat and hamster

PubMed Central

Sanford, P. A.; Smyth, D. H.

1971-01-01

1. The transfer of choline was studied with sacs of everted intestine of rat and hamster. 2. The choline transfer can be divided into two components, a diffusion process and a saturable process. The latter plays a relatively greater part at low concentrations of choline, which include the physiological concentration in the plasma. The saturable process is better seen in the hamster than in the rat. 3. Intestinal transfer of choline is influenced by substances altering the availability of energy in the cell, and by some substances chemically or pharmacologically related to choline. These findings are consistent with some kind of specific mechanism for choline transfer. 4. Part of the choline taken up by the cell appears as a metabolite not yet identified. The formation of the metabolite is a saturable process and is abolished by anaerobic conditions and by homogenization. 5. The results are also discussed in relation to parameters of transfer. PMID:5090994

Laser processes and system technology for the production of high-efficient crystalline solar cells

NASA Astrophysics Data System (ADS)

Mayerhofer, R.; Hendel, R.; Zhu, Wenjie; Geiger, S.

2012-10-01

The laser as an industrial tool is an essential part of today's solar cell production. Due to the on-going efforts in the solar industry, to increase the cell efficiency, more and more laser-based processes, which have been discussed and tested at lab-scale for many years, are now being implemented in mass production lines. In order to cope with throughput requirements, standard laser concepts have to be improved continuously with respect to available average power levels, repetition rates or beam profile. Some of the laser concepts, that showed high potential in the past couple of years, will be substituted by other, more economic laser types. Furthermore, requirements for processing with less-heat affected zones fuel the development of industry-ready ultra short pulsed lasers with pulse widths even below the picosecond range. In 2011, the German Ministry of Education and Research (BMBF) had launched the program "PV-Innovation Alliance", with the aim to support the rapid transfer of high-efficiency processes out of development departments and research institutes into solar cell production lines. Here, lasers play an important role as production tools, allowing the fast implementation of high-performance solar cell concepts. We will report on the results achieved within the joint project FUTUREFAB, where efficiency optimization, throughput enhancement and cost reduction are the main goals. Here, the presentation will focus on laser processes like selective emitter doping and ablation of dielectric layers. An indispensable part of the efforts towards cost reduction in solar cell production is the improvement of wafer handling and throughput capabilities of the laser processing system. Therefore, the presentation will also elaborate on new developments in the design of complete production machines.

The stem cell laboratory: design, equipment, and oversight.

PubMed

Wesselschmidt, Robin L; Schwartz, Philip H

2011-01-01

This chapter describes some of the major issues to be considered when setting up a laboratory for the culture of human pluripotent stem cells (hPSCs). The process of establishing a hPSC laboratory can be divided into two equally important parts. One is completely administrative and includes developing protocols, seeking approval, and establishing reporting processes and documentation. The other part of establishing a hPSC laboratory involves the physical plant and includes design, equipment and personnel. Proper planning of laboratory operations and proper design of the physical layout of the stem cell laboratory so that meets the scope of planned operations is a major undertaking, but the time spent upfront will pay long-term returns in operational efficiency and effectiveness. A well-planned, organized, and properly equipped laboratory supports research activities by increasing efficiency and reducing lost time and wasted resources.

Engineering cells for cell culture bioprocessing--physiological fundamentals.

PubMed

Seth, Gargi; Hossler, Patrick; Yee, Joon Chong; Hu, Wei-Shou

2006-01-01

In the past decade, we have witnessed a tremendous increase in the number of mammalian cell-derived therapeutic proteins with clinical applications. The success of making these life-saving biologics available to the public is partly due to engineering efforts to enhance process efficiency. To further improve productivity, much effort has been devoted to developing metabolically engineered producing cells, which possess characteristics favorable for large-scale bioprocessing. In this article we discuss the fundamental physiological basis for cell engineering. Different facets of cellular mechanisms, including metabolism, protein processing, and the balancing pathways of cell growth and apoptosis, contribute to the complex traits of favorable growth and production characteristics. We present our assessment of the current state of the art by surveying efforts that have already been undertaken in engineering cells for a more robust process. The concept of physiological homeostasis as a key determinant and its implications on cell engineering is emphasized. Integrating the physiological perspective with cell culture engineering will facilitate attainment of dream cells with superlative characteristics.

Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation

PubMed Central

Kopko, Patricia M.

2016-01-01

Summary ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation. PMID:27022318

Fault Detection and Diagnosis In Hall-Héroult Cells Based on Individual Anode Current Measurements Using Dynamic Kernel PCA

NASA Astrophysics Data System (ADS)

Yao, Yuchen; Bao, Jie; Skyllas-Kazacos, Maria; Welch, Barry J.; Akhmetov, Sergey

2018-04-01

Individual anode current signals in aluminum reduction cells provide localized cell conditions in the vicinity of each anode, which contain more information than the conventionally measured cell voltage and line current. One common use of this measurement is to identify process faults that can cause significant changes in the anode current signals. While this method is simple and direct, it ignores the interactions between anode currents and other important process variables. This paper presents an approach that applies multivariate statistical analysis techniques to individual anode currents and other process operating data, for the detection and diagnosis of local process abnormalities in aluminum reduction cells. Specifically, since the Hall-Héroult process is time-varying with its process variables dynamically and nonlinearly correlated, dynamic kernel principal component analysis with moving windows is used. The cell is discretized into a number of subsystems, with each subsystem representing one anode and cell conditions in its vicinity. The fault associated with each subsystem is identified based on multivariate statistical control charts. The results show that the proposed approach is able to not only effectively pinpoint the problematic areas in the cell, but also assess the effect of the fault on different parts of the cell.

KSC-2011-8289

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians secure space shuttle Atlantis’ three fuel cells to special platforms. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

Determining the Origin of Human Germinal Center B Cell-Derived Malignancies.

PubMed

Seifert, Marc; Küppers, Ralf

2017-01-01

Most human B cell lymphomas originate from germinal center (GC) B cells. This is partly caused by the high proliferative activity of GC B cells and the remodeling processes acting at the immunoglobulin (Ig) loci of these cells, i.e., somatic hypermutation and class-switching. Mistargeting of these processes can cause chromosomal translocations, and the hypermutation machinery may also target non-Ig genes. As somatic hypermutation is exclusively active in GC B cells, the presence of somatic mutations in rearranged IgV genes is a standard criterium for a GC or post-GC B cell origin of lymphomas. Beyond this, ongoing somatic hypermutation during lymphoma clone expansion indicates that the lymphoma has an active GC B cell differentiation program. The proto-oncogene BCL6 is specifically expressed in GC B cells and also acquires somatic mutations as a physiological by-product of the somatic hypermutation process, albeit at a lower level than IgV genes. Thus, detection of BCL6 mutations is a further genetic trait of a GC experience of a B cell lymphoma. Typically, B cell lymphomas retain key features of their specific cells of origin, including a differentiation stage-specific gene expression pattern. This is at least partly due to genetic lesions, which "freeze" the lymphoma cells at the differentiation stage at which the transformation occurred. Therefore, identification of the normal B cell subset with the most similar gene expression pattern to a particular type of B cell lymphoma has been instrumental to deduce the precise cell of origin of lymphomas.We present here protocols to analyze human B cell lymphomas for a potential origin from GC B cells by determining the presence of mutations in rearranged IgV genes and the BCL6 gene, and by comparing the gene expression pattern of lymphoma cells with those of normal B cell subsets by genechip or RNA-sequencing analysis.

The Stem Cell Laboratory: Design, Equipment, and Oversight

PubMed Central

Wesselschmidt, Robin L.; Schwartz, Philip H.

2013-01-01

This chapter describes some of the major issues to be considered when setting up a laboratory for the culture of human pluripotent stem cells (hPSCs). The process of establishing a hPSC laboratory can be divided into two equally important parts. One is completely administrative and includes developing protocols, seeking approval, and establishing reporting processes and documentation. The other part of establishing a hPSC laboratory involves the physical plant and includes design, equipment and personnel. Proper planning of laboratory operations and proper design of the physical layout of the stem cell laboratory so that meets the scope of planned operations is a major undertaking, but the time spent upfront will pay long-term returns in operational efficiency and effectiveness. A well-planned, organized, and properly equipped laboratory supports research activities by increasing efficiency and reducing lost time and wasted resources. PMID:21822863

Peripheral sensory processing in mammalian gravity receptors - Observations of ciliary tuft configurations

NASA Technical Reports Server (NTRS)

Ross, Muriel D.; Donovan, Kathleen; Rogers, Charles

1987-01-01

Scanning electron microscopy was used to study dynamic polarizations of clustered cells of the anterior part of rat saccular macula and to shed light on the possible roles of two types of hair cells integrated into the same neural circuitry: those with short stereocilia and long kinocilium (ss/lk), and those with long stereocilia and still longer kinocilium (ls/lk). It was found that the ss/lk-type cells could be further subdivided into two types, whereas the ls/lk cells consisted of four major kinds. It was also found that the kinocilium was most often fixed in a recovery stroke position (curved basally, and the upper portion projected back over the tuft) and that the kinocilia were not aligned in parallel in any given part of a macula, even though each cilium pointed in the proper direction relative to the striola line. The possibility of a relationship between the ciliary tuft morphology and the function of the hair cell of which it is a part is discussed.

Heat exchange studies on coconut oil cells as thermal energy storage for room thermal conditioning

NASA Astrophysics Data System (ADS)

Sutjahja, I. M.; Putri, Widya A.; Fahmi, Z.; Wonorahardjo, S.; Kurnia, D.

2017-07-01

As reported by many thermal environment experts, room air conditioning might be controlled by thermal mass system. In this paper we discuss the performance of coconut oil cells as room thermal energy storage. The heat exchange mechanism of coconut oil (CO) which is one of potential organic Phase Change Material (PCM) is studied based on the results of temperature measurements in the perimeter and core parts of cells. We found that the heat exchange performance, i.e. heat absorption and heat release processes of CO cells are dominated by heat conduction in the sensible solid from the higher temperature perimeter part to the lower temperature core part and heat convection during the solid-liquid phase transition and sensible liquid phase. The capability of heat absorption as measured by the reduction of air temperature is not influenced by CO cell size. Besides that, the application of CO as the thermal mass has to be accompanied by air circulation to get the cool sensation of the room’s occupants.

Germ cell cluster organization and oogenesis in the tardigrade Dactylobiotus parthenogeneticus Bertolani, 1982 (Eutardigrada, Murrayidae).

PubMed

Poprawa, Izabela; Hyra, Marta; Rost-Roszkowska, Magdalena Maria

2015-07-01

Germ cell cluster organization and the process of oogenesis in Dactylobiotus parthenogeneticus have been described using transmission electron microscopy and light microscopy. The reproductive system of D. parthenogeneticus is composed of a single, sac-like, meroistic ovary and a single oviduct that opens into the cloaca. Two zones can be distinguished in the ovary: a small germarium that is filled with oogonia and a vitellarium that is filled with germ cell clusters. The germ cell cluster, which has the form of a modified rosette, consists of eight cells that are interconnected by stable cytoplasmic bridges. The cell that has the highest number of stable cytoplasmic bridges (four bridges) finally develops into the oocyte, while the remaining cells become trophocytes. Vitellogenesis of a mixed type occurs in D. parthenogeneticus. One part of the yolk material is produced inside the oocyte (autosynthesis), while the second part is synthesized in the trophocytes and transported to the oocyte through the cytoplasmic bridges. The eggs are covered with two envelopes: a thin vitelline envelope and a three-layered chorion. The surface of the chorion forms small conical processes, the shape of which is characteristic for the species that was examined. In our paper, we present the first report on the rosette type of germ cell clusters in Parachela.

Genetic changes in mammalian cells transformed by helium ions

NASA Astrophysics Data System (ADS)

Durante, M.; Grossi, G.; Yang, T. C.; Roots, R.

Midterm Syrian Hamster embryo (SHE) cells were employed to study high LET-radiation induced tumorigenesis. Normal SHE cells (secondary passage) were irradiated with accelerated helium ions at an incident energy of 22 MeV/u (9-10 keV/μm). Transformed clones were isolated after growth in soft agar of cells obtained from the foci of the initial monolayer plated postirradiation. To study the progression process of malignant transformation, the transformed clones were followed by monolayer subculturing for prolonged periods of time. Subsequently, neoplasia tests in nude mice were done. In this work, however, we have focused on karyotypic changes in the banding patterns of the chromosomes during the early part of the progressive process of cell transformation for helium ion-induced transformed cells.

Development of lithium diffused radiation resistant solar cells, part 2

NASA Technical Reports Server (NTRS)

Payne, P. R.; Somberg, H.

1971-01-01

The work performed to investigate the effect of various process parameters on the performance of lithium doped P/N solar cells is described. Effort was concentrated in four main areas: (1) the starting material, (2) the boron diffusion, (3) the lithium diffusion, and (4) the contact system. Investigation of starting material primarily involved comparison of crucible grown silicon (high oxygen content) and Lopex silicon (low oxygen content). In addition, the effect of varying growing parameters of crucible grown silicon on lithium cell output was also examined. The objective of the boron diffusion studies was to obtain a diffusion process which produced high efficiency cells with minimal silicon stressing and could be scaled up to process 100 or more cells per diffusion. Contact studies included investigating sintering of the TiAg contacts and evaluation of the contact integrity.

The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology.

PubMed

Hegyi, Peter; Petersen, Ole H

2013-01-01

There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other.

Novel tag-and-exchange (RMCE) strategies generate master cell clones with predictable and stable transgene expression properties.

PubMed

Qiao, Junhua; Oumard, André; Wegloehner, Wolfgang; Bode, Juergen

2009-07-24

Site-specific recombinases have revolutionized the systematic generation of transgenic cell lines and embryonic stem cells/animals and will ultimately also reveal their potential in the genetic modification of induced pluripotent stem cells. Introduced in 1994, our Flp recombinase-mediated cassette exchange strategy permits the exchange of a target cassette for a cassette with the gene of interest, introduced as a part of an exchange vector. The process is "clean" in the sense that it does not co-introduce prokaryotic vector parts; neither does it leave behind a selection marker. Stringent selection principles provide master cell lines permitting subsequent recombinase-mediated cassette exchange cycles in the absence of a drug selection and with a considerable efficiency (approximately 10%). Exemplified by Chinese hamster ovary cells, the strategy proves to be successful even for cell lines with an unstable genotype.

Tensegrity I. Cell structure and hierarchical systems biology

NASA Technical Reports Server (NTRS)

Ingber, Donald E.

2003-01-01

In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

Biobehavioral Development. From Cells to Selves.

ERIC Educational Resources Information Center

National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

Key to the mission of the National Institute of Child Health and Human Development (NICHD) is answering fundamental questions about how a single fertilized cell eventually develops into a fully functional adult human being and how a multitude of genetic and environmental factors influence that process. This document details part of NICHD's…

Developmental mechanisms regulating secondary growth in woody plants

Treesearch

Andrew Groover; Marcel Robischon

2006-01-01

Secondary growth results in the radial expansion of woody stems, and requires the coordination of tissue patterning, cell differentiation, and the maintenance of meristematic stem cells within the vascular cambium. Advances are being made towards describing molecular mechanisms that regulate these developmental processes, thanks in part to the application of new...

Development of a robust, versatile, and scalable inoculum train for the production of a DNA vaccine.

PubMed

Okonkowski, J; Kizer-Bentley, L; Listner, K; Robinson, D; Chartrain, M

2005-01-01

For many microbial fermentation processes, the inoculum train can have a substantial impact on process performance in terms of productivity, profitability, and process control. In general, it is understood that a well-characterized and flexible inoculum train is essential for future scale-up and implementation of the process in a pilot plant or manufacturing setting. A fermentation process utilizing E. coli DH5 for the production of plasmid DNA carrying the HIV gag gene for use as a vaccine is currently under development in our laboratory. As part of the development effort, we evaluated inoculum train schemes that incorporate one, two, or three stages. In addition, we investigated the effect of inoculum viable-cell concentrations, either thawed or actively growing, over a wide range (from 2.5 x 10(4) to 1.0 x 10(8) viable cells/mL or approximately 0.001% to 4% of final working volume). The various inoculum trains were evaluated in terms of final plasmid yield, process time, reproducibility, robustness, and feasibility at large scale. The results of these studies show that final plasmid yield remained in the desired range, despite the number of stages or inoculation viable-cell concentrations comprising the inoculum train. On the basis of these observations and because it established a large database, the first part of these investigations supports an exceptional flexibility in the design of scalable inoculum trains for this DNA vaccine process. This work also highlighted that a slightly higher level of process reproducibility, as measured by the time for the culture to reach mid-exponential growth, was observed when using actively growing versus frozen cells. It also demonstrated the existence of a viable-cell concentration threshold for the one-stage process, since we observed that inoculation of the production stage with very low amounts of viable cells from a frozen source could lead to increased process sensitivity to external factors such as variation in the quality of the raw materials used in the medium formulation. However, our analysis indicates that, despite this slight disadvantage, a one-stage inoculum train was a viable option in many situations, especially if the inoculation viable-cell concentration was kept above 4.8 x 10(6) viable cells/mL. Because it leads to a reduction in process steps and eliminates some capital investments (i.e., inoculum fermenter), when feasible a one-stage process configuration will positively impact process economics.

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

Perfusion mammalian cell culture for recombinant protein manufacturing - A critical review.

PubMed

Bielser, Jean-Marc; Wolf, Moritz; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo

The manufacturing of recombinant protein is traditionally divided in two main steps: upstream (cell culture and synthesis of the target protein) and downstream (purification and formulation of the protein into a drug substance or drug product). Today, cost pressure, market uncertainty and market growth, challenge the existing manufacturing technologies. Leaders in the field are active in designing the process of the future and continuous manufacturing is recurrently mentioned as a potential solution to address some of the current limitations. This review focuses on the application of continuous processing to the first step of the manufacturing process. Enabling technologies and operation modes are described in the first part. In the second part, recent advances in the field that have the potential to support its successful future development are critically discussed. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Quality Saving Mechanisms of Mitochondria during Aging in a Fully Time-Dependent Computational Biophysical Model

PubMed Central

Mellem, Daniel; Fischer, Frank; Jaspers, Sören; Wenck, Horst; Rübhausen, Michael

2016-01-01

Mitochondria are essential for the energy production of eukaryotic cells. During aging mitochondria run through various processes which change their quality in terms of activity, health and metabolic supply. In recent years, many of these processes such as fission and fusion of mitochondria, mitophagy, mitochondrial biogenesis and energy consumption have been subject of research. Based on numerous experimental insights, it was possible to qualify mitochondrial behaviour in computational simulations. Here, we present a new biophysical model based on the approach of Figge et al. in 2012. We introduce exponential decay and growth laws for each mitochondrial process to derive its time-dependent probability during the aging of cells. All mitochondrial processes of the original model are mathematically and biophysically redefined and additional processes are implemented: Mitochondrial fission and fusion is separated into a metabolic outer-membrane part and a protein-related inner-membrane part, a quality-dependent threshold for mitophagy and mitochondrial biogenesis is introduced and processes for activity-dependent internal oxidative stress as well as mitochondrial repair mechanisms are newly included. Our findings reveal a decrease of mitochondrial quality and a fragmentation of the mitochondrial network during aging. Additionally, the model discloses a quality increasing mechanism due to the interplay of the mitophagy and biogenesis cycle and the fission and fusion cycle of mitochondria. It is revealed that decreased mitochondrial repair can be a quality saving process in aged cells. Furthermore, the model finds strategies to sustain the quality of the mitochondrial network in cells with high production rates of reactive oxygen species due to large energy demands. Hence, the model adds new insights to biophysical mechanisms of mitochondrial aging and provides novel understandings of the interdependency of mitochondrial processes. PMID:26771181

Red cell surface changes in cold agglutination

PubMed Central

Salsbury, A. J.; Clarke, J. A.; Shand, W. S.

1968-01-01

Surface changes in red blood cells undergoing cold agglutination have been investigated using the Cambridge Stereoscan electron microscope. On incubation of red cells with a cold agglutinin of anti-I specificity at 4°C, circular shadows on the red cell membrane developed within 2 min. At the same time the membrane showed a granularity and processes began to develop on the surface. These processes increased in length, the processes of contiguous cells became interlinked and agglutination was complete after incubation of 1 hr. On warming an agglutinated specimen, the process was reversed with separation of red cells and retraction of the finger-like processes to yield discrete red cells of normal appearance. The addition of heparin in vivo prevented agglutination but did not inhibit surface changes completely. Complement appeared to play no part in the production of cold agglutination due to these antibodies or in the reversal of agglutination by warming. The significance of the surface changes described in relation to previous information on the mechanism of agglutination, has been discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11 PMID:5655472

Color in the Cortex—single- and double-opponent cells

PubMed Central

Shapley, Robert; Hawken, Michael

2011-01-01

This is a review of the research during the past 25 years on cortical processing of color signals. At the beginning of the period the modular view of cortical processing predominated. However, at present an alternative view, that color and form are linked inextricably in visual cortical processing, is more persuasive than it seemed in 1985. Also, the role of the primary visual cortex, V1, in color processing now seems much larger than it did in 1985. The re-evaluation of the important role of V1 in color vision was caused in part by investigations of human V1 responses to color, measured with functional magnetic resonance imaging, fMRI, and in part by the results of numerous studies of single-unit neurophysiology in non-human primates. The neurophysiological results have highlighted the importance of double-opponent cells in V1. Another new concept is population coding of hue, saturation, and brightness in cortical neuronal population activity. PMID:21333672

Arithmetic of five-part of leukocytes based on image process

NASA Astrophysics Data System (ADS)

Li, Yian; Wang, Guoyou; Liu, Jianguo

2007-12-01

This paper apply computer image processing and pattern recognizition methods to solve the problem of auto classification and counting of leukocytes (white blood cell) in peripheral blood. In this paper a new leukocyte arithmetic of five-part based on image process and pattern recognizition is presented, which relized auto classify of leukocyte. The first aim is detect the leukocytes . A major requirement of the whole system is to classify these leukocytes to 5 classes. This arithmetic bases on notability mechanism of eyes, process image by sequence, divides up leukocytes and pick up characters. Using the prior kwonledge of cells and image shape information, this arithmetic divides up the probable shape of Leukocyte first by a new method based on Chamfer and then gets the detail characters. It can reduce the mistake judge rate and the calculation greatly. It also has the learning fuction. This paper also presented a new measurement of karyon's shape which can provide more accurate information. This algorithm has great application value in clinical blood test .

Self-Elongation with Sequential Folding of a Filament of Bacterial Cells

NASA Astrophysics Data System (ADS)

Honda, Ryojiro; Wakita, Jun-ichi; Katori, Makoto

2015-11-01

Under hard-agar and nutrient-rich conditions, a cell of Bacillus subtilis grows as a single filament owing to the failure of cell separation after each growth and division cycle. The self-elongating filament of cells shows sequential folding processes, and multifold structures extend over an agar plate. We report that the growth process from the exponential phase to the stationary phase is well described by the time evolution of fractal dimensions of the filament configuration. We propose a method of characterizing filament configurations using a set of lengths of multifold parts of a filament. Systems of differential equations are introduced to describe the folding processes that create multifold structures in the early stage of the growth process. We show that the fitting of experimental data to the solutions of equations is excellent, and the parameters involved in our model systems are determined.

Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science.

PubMed

Lenas, Petros; Moos, Malcolm; Luyten, Frank P

2009-12-01

The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has developed the necessary concepts and methods to describe it, allowing therefore a deeper understanding of the behavior of networks during biomimetic processes. These advances thus open the door to a transition for tissue engineering from a substantially empirical endeavor to a technology-based discipline comparable to other branches of engineering.

Comparison between Palm Oil Derivative and Commercial Thermo-Plastic Binder System on the Properties of the Stainless Steel 316L Sintered Parts

NASA Astrophysics Data System (ADS)

Ibrahim, R.; Azmirruddin, M.; Wei, G. C.; Fong, L. K.; Abdullah, N. I.; Omar, K.; Muhamad, M.; Muhamad, S.

2010-03-01

Binder system is one of the most important criteria for the powder injection molding (PIM) process. Failure in the selection of the binder system will affect on the final properties of the sintered parts. The objectives of this studied is to develop a novel binder system based on the local natural resources and environmental friendly binder system from palm oil derivative which is easily available and cheap in our country of Malaysia. The novel binder that has been developed will be replaced the commercial thermo-plastic binder system or as an alternative binder system. The results show that the physical and mechanical properties of the final sintered parts fulfill the Metal Powder Industries Federation (MPIF) standard 35 for PIM parts. The biocompatibility test using cell osteosarcoma (MG63) and vero fibroblastic also shows that the cell was successfully growth on the sintered stainless steel 316L parts indicate that the novel binder was not toxic. Therefore, the novel binder system based on palm oil derivative that has been developed as a binder system fulfills the important criteria for the binder system in PIM process.

KSC-2011-8280

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, space shuttle Atlantis’ three fuel cells are being removed from the payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8276

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians prepare to remove one of three fuel cells from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8277

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians prepare to remove one of three fuel cells from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

Processing of Cells' Trajectories Data for Blood Flow Simulation Model*

NASA Astrophysics Data System (ADS)

Slavík, Martin; Kovalčíková, Kristína; Bachratý, Hynek; Bachratá, Katarína; Smiešková, Monika

2018-06-01

Simulations of the red blood cells (RBCs) flow as a movement of elastic objects in a fluid, are developed to optimize microfluidic devices used for a blood sample analysis for diagnostic purposes in the medicine. Tracking cell behaviour during simulation helps to improve the model and adjust its parameters. For the optimization of the microfluidic devices, it is also necessary to analyse cell trajectories as well as likelihood and frequency of their occurrence in a particular device area, especially in the parts, where they can affect circulating tumour cells capture. In this article, we propose and verify several ways of processing and analysing the typology and trajectory stability in simulations with single or with a large number of red blood cells (RBCs) in devices with different topologies containing cylindrical obstacles.

Setting the Stage for Personalized Treatment of Glioma | Center for Cancer Research

Cancer.gov

Gliomas, the most common type of primary brain tumors in adults, arise from different types of glial cells, which support and protect the neurons of the central nervous system. How a patient’s glioma is treated depends in part on the type of glial cell from which the tumor developed. Classification of gliomas has traditionally been done by microscopic analysis of tumor sections. This process is subjective and prone to inconsistencies, which may explain in part the wide-ranging and often suboptimal responses of gliomas to treatment.  

From bench to FDA to bedside: US regulatory trends for new stem cell therapies.

PubMed

Knoepfler, Paul S

2015-03-01

The phrase "bench-to-bedside" is commonly used to describe the translation of basic discoveries such as those on stem cells to the clinic for therapeutic use in human patients. However, there is a key intermediate step in between the bench and the bedside involving governmental regulatory oversight such as by the Food and Drug Administration (FDA) in the United States (US). Thus, it might be more accurate in most cases to describe the stem cell biological drug development process in this way: from bench to FDA to bedside. The intermediate development and regulatory stage for stem cell-based biological drugs is a multifactorial, continually evolving part of the process of developing a biological drug such as a stem cell-based regenerative medicine product. In some situations, stem cell-related products may not be classified as biological drugs in which case the FDA plays a relatively minor role. However, this middle stage is generally a major element of the process and is often colloquially referred to in an ominous way as "The Valley of Death". This moniker seems appropriate because it is at this point, and in particular in the work that ensues after Phase 1, clinical trials that most drug product development is terminated, often due to lack of funding, diseases being refractory to treatment, or regulatory issues. Not surprisingly, workarounds to deal with or entirely avoid this difficult stage of the process are evolving both inside and outside the domains of official regulatory authorities. In some cases these efforts involve the FDA invoking new mechanisms of accelerating the bench to beside process, but in other cases these new pathways bypass the FDA in part or entirely. Together these rapidly changing stem cell product development and regulatory pathways raise many scientific, ethical, and medical questions. These emerging trends and their potential consequences are reviewed here. Copyright © 2014 Elsevier B.V. All rights reserved.

Nano-Aramid Fiber Reinforced Polyurethane Foam

NASA Technical Reports Server (NTRS)

Semmes, Edmund B.; Frances, Arnold

2008-01-01

Closed cell polyurethane and, particularly, polyisocyanurate foams are a large family of flexible and rigid products the result of a reactive two part process wherein a urethane based polyol is combined with a foaming or "blowing" agent to create a cellular solid at room temperature. The ratio of reactive components, the constituency of the base materials, temperature, humidity, molding, pouring, spraying and many other processing techniques vary greatly. However, there is no known process for incorporating reinforcing fibers small enough to be integrally dispersed within the cell walls resulting in superior final products. The key differentiating aspect from the current state of art resides in the many processing technologies to be fully developed from the novel concept of milled nano pulp aramid fibers and their enabling entanglement capability fully enclosed within the cell walls of these closed cell urethane foams. The authors present the results of research and development of reinforced foam processing, equipment development, strength characteristics and the evolution of its many applications.

ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

PubMed Central

Teixeira, Felipe K.; Sanchez, Carlos G.; Hurd, Thomas R.; Seifert, Jessica R. K.; Czech, Benjamin; Preall, Jonathan B.; Hannon, Gregory J.; Lehmann, Ruth

2015-01-01

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation. PMID:25915123

Dissection of enhanced cell expansion processes in leaves triggered by a defect in cell proliferation, with reference to roles of endoreduplication.

PubMed

Fujikura, Ushio; Horiguchi, Gorou; Tsukaya, Hirokazu

2007-02-01

Leaf development relies on cell proliferation, post-mitotic cell expansion and the coordination of these processes. In several Arabidopsis thaliana mutants impaired in cell proliferation, such as angustifolia3 (an3), leaf cells are larger than normal at their maturity. This phenomenon, which we call compensated cell enlargement, suggests the presence of such coordination in leaf development. To dissect genetically the cell expansion system(s) underlying this compensation seen in the an3 mutant, we isolated and utilized 10 extra-small sisters (xs) mutant lines that show decreased cell size but normal cell numbers in leaves. In the xs single mutants, the palisade cell sizes in mature leaves are about 20-50% smaller than those of wild-type cells. Phenotypes of the palisade cell sizes in all combinations of xs an3 double mutants fall into three classes. In the first class, the compensated cell enlargement was significantly suppressed. Conversely, in the second class, the defective cell expansion conferred by the xs mutations was significantly suppressed by the an3 mutation. The residual xs mutations had effects additive to those of the an3 mutation on cell expansion. The endopolyploidy levels in the first class of mutants were decreased, unaffected or increased, as compared with those in wild-type, suggesting that the abnormally enhanced cell expansion observed in an3 could be mediated, at least in part, by ploidy-independent mechanisms. Altogether, these results clearly showed that a defect in cell proliferation in leaf primordia enhances a part of the network that regulates cell expansion, which is required for normal leaf expansion.

DIAC object recognition system

NASA Astrophysics Data System (ADS)

Buurman, Johannes

1992-03-01

This paper describes the object recognition system used in an intelligent robot cell. It is used to recognize and estimate pose and orientation of parts as they enter the cell. The parts are mostly metal and consist of polyhedral and cylindrical shapes. The system uses feature-based stereo vision to acquire a wireframe of the observed part. Features are defined as straight lines and ellipses, which lead to a wireframe of straight lines and circular arcs (the latter using a new algorithm). This wireframe is compared to a number of wire frame models obtained from the CAD database. Experimental results show that image processing hardware and parallelization may add considerably to the speed of the system.

The intersection between DNA damage response and cell death pathways.

PubMed

Nowsheen, S; Yang, E S

2012-10-01

Apoptosis is a finely regulated process that serves to determine the fate of cells in response to various stresses. One such stress is DNA damage, which not only can signal repair processes but is also intimately involved in regulating cell fate. In this review we examine the relationship between the DNA damage/repair response in cell survival and apoptosis following insults to the DNA. Elucidating these pathways and the crosstalk between them is of great importance, as they eventually contribute to the etiology of human disease such as cancer and may play key roles in determining therapeutic response. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

Spraylon fluorocarbon encapsulation for silicon solar cell arrays

NASA Technical Reports Server (NTRS)

1977-01-01

A development program was performed for evaluating, modifying, and optimizing the Lockheed formulated liquid transparent filmforming Spraylon fluorocarbon protective coating for silicon solar cells and modules. The program objectives were designed to meet the requirements of the low-cost automated solar cell array fabrication process. As part of the study, a computer program was used to establish the limits of the safe working stress in the coated silicon solar cell array system under severe thermal shock.

Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

NASA Astrophysics Data System (ADS)

Koch, Alisa E.; Halloran, Margaret M.; Haskell, Catherine J.; Shah, Manisha R.; Polverini, Peter J.

1995-08-01

ENDOTHELIAL adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumour growth and wound repair1. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis2á¤-4. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.

Dynamics of asexual reproduction in planarians

NASA Astrophysics Data System (ADS)

Schoetz, Eva-Maria; Lincoln, Bryan; Quinodoz, Sofia

2011-03-01

Planaria research is experiencing a resurgence due to the development of molecular tools, the Planarian genome project and database resources. Despite the resulting progress in planarian biology research, an extensive study of their physical properties remains to be undertaken. We developed a method to collect a large amount of data on the dynamics of clonal reproduction in the freshwater planarian S.mediterranea. The capability of planarians to regenerate an entire organism from a minuscule body part is based on a homogeneously distributed stem cell population that comprises 25-30% of all cells. Due to this stem cell contingent, planarians can reproduce spontaneously by dividing into a larger head and a smaller tail piece, which then will rebuild the missing body parts, including a central nervous system, within about a week. Time-lapse imaging allows us to characterize the fission process in detail, revealing the stages of the process as well as capturing the nature of the rupture itself. A traction force measurement setup is being developed to allow us to quantify the forces planarians exert on the substrate during reproduction, a macroscopic analog to the Traction Force Microscopy setups used to determine local cellular forces. We are particularly interested in the molecular processes during division and the interplay between tissue mechanics and cell signaling.

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells

PubMed Central

Maes, Margaret E.; Schlamp, Cassandra L.; Nickells, Robert W.

2017-01-01

Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma. PMID:28064040

BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells.

PubMed

Maes, Margaret E; Schlamp, Cassandra L; Nickells, Robert W

2017-03-01

Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death. A major component of this process is the complex interaction of members of the BCL2 gene family. Three distinct family members of proteins orchestrate the most critical junction in the apoptotic program of RGCs, culminating in the activation of pro-apoptotic BAX. Once active, BAX causes irreparable damage to mitochondria, while precipitating downstream events that finish off a dying ganglion cell. This review is divided into two major parts. First, we summarize the extent of knowledge of how BCL2 gene family proteins interact to facilitate the activation and function of BAX. This area of investigation has rapidly changed over the last few years and has yielded a dramatically different mechanistic understanding of how the intrinsic apoptotic program is run in mammalian cells. Second, we provided a comprehensive analysis of nearly two decades of investigation of the role of BAX in the process of RGC death, much of which has provided many important insights into the overall pathophysiology of diseases like glaucoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Your Eyes

MedlinePlus

... that nourishes the eye and keeps it healthy. Light, Lens, Action These next parts are really cool, ... back of the eye. Rods and Cones Process Light The retina uses special cells called rods and ...

Electro-optic characteristics of 4-domain vertical alignment nematic liquid crystal display with interdigital electrode

NASA Astrophysics Data System (ADS)

Hong, S. H.; Jeong, Y. H.; Kim, H. Y.; Cho, H. M.; Lee, W. G.; Lee, S. H.

2000-06-01

We have fabricated a vertically aligned 4-domain nematic liquid crystal display cell with thin film transistor. Unlike the conventional method constructing 4-domain, i.e., protrusion and surrounding electrode which needs additional processes, in this study the pixel design forming 4-domain with interdigital electrodes is suggested. In the device, one pixel is divided into two parts. One part has a horizontal electric field in the vertical direction and the other part has a horizontal one in the horizontal direction. Such fields in the horizontal and vertical direction drive the liquid crystal director to tilt down in four directions. In this article, the electro-optic characteristics of cells with 2 and 4 domain have been studied. The device with 4 domain shows faster response time than normal twisted-nematic and in-plane switching cells, wide viewing angle with optical compensation film, and more stable color characteristics than 2-domain vertical alignment cell with similar structure.

Müller cells separate between wavelengths to improve day vision with minimal effect upon night vision

NASA Astrophysics Data System (ADS)

Labin, Amichai M.; Safuri, Shadi K.; Ribak, Erez N.; Perlman, Ido

2014-07-01

Vision starts with the absorption of light by the retinal photoreceptors—cones and rods. However, due to the ‘inverted’ structure of the retina, the incident light must propagate through reflecting and scattering cellular layers before reaching the photoreceptors. It has been recently suggested that Müller cells function as optical fibres in the retina, transferring light illuminating the retinal surface onto the cone photoreceptors. Here we show that Müller cells are wavelength-dependent wave-guides, concentrating the green-red part of the visible spectrum onto cones and allowing the blue-purple part to leak onto nearby rods. This phenomenon is observed in the isolated retina and explained by a computational model, for the guinea pig and the human parafoveal retina. Therefore, light propagation by Müller cells through the retina can be considered as an integral part of the first step in the visual process, increasing photon absorption by cones while minimally affecting rod-mediated vision.

Endothelial cells promote the proliferation of lymphocytes partly through the Wnt pathway via LEF-1

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

Wang, Shu-Hong; Nan, Ke-Jun, E-mail: nankj@163.com; Wang, Yao-Chun

The function of T cells and B cells is to recognize specific 'non-self' antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. Endothelial cells (ECs) can trigger the activation of T cells through their class I and class II MHC molecules. In this study, we examined the effect of ECs on the proliferation of lymphocytes. We report that the proliferation of T and B cells can be improved by interaction with ECs. LEF-1 is one of the main molecularmore » mediators in this process, and the inhibition of LEF-1 induces apoptosis. These results suggest that LEF-1 modulates positively the proliferation of lymphocytes induced by their interaction with ECs.« less

Technology advancement of the electrochemical CO2 concentrating process

NASA Technical Reports Server (NTRS)

Schubert, F. H.; Woods, R. R.; Hallick, T. M.; Heppner, D. B.

1977-01-01

A five-cell, liquid-cooled advanced electrochemical depolarized carbon dioxide concentrator module was fabricated. The cells utilized the advanced, lightweight, plated anode current collector concept and internal liquid-cooling. The five cell module was designed to meet the carbon dioxide removal requirements of one man and was assembled using plexiglass endplates. This one-man module was tested as part of an integrated oxygen generation and recovery subsystem.

Research, Development and Fabrication of Lithium Solar Cells, Part 2

NASA Technical Reports Server (NTRS)

Iles, P. A.

1972-01-01

The development and fabrication of lithium solar cells are discussed. Several single-step, lithium diffusion schedules using lower temperatures and times are described. A comparison was made using evaporated lithium metal as the lithium source, and greatly improved consistency in lithium concentrations was obtained. It was possible to combine all processing steps to obtain lithium doped cells of high output which also contained adequate lithium to ensure good recoverability.

Micromechanical Devices for Control of Cell-Cell Interaction, and Methods of Use Thereof

NASA Technical Reports Server (NTRS)

Bhatia, Sangeeta N. (Inventor); Hui, Elliot (Inventor)

2017-01-01

The development and function of living tissues depends largely on interactions between cells that can vary in both time and space; however, temporal control of cell-cell interaction is experimentally challenging. By employing a micromachined silicon substrate with moving parts, herein is disclosed the dynamic regulation of cell-cell interactions via direct manipulation of adherent cells with micron-scale precision. The inventive devices and methods allow mechanical control of both tissue composition and spatial organization. The inventive device and methods enable the investigation of dynamic cell-cell interaction in a multitude of applications, such as intercellular communication, spanning embryogenesis, homeostasis, and pathogenic processes.

The epithelial-mesenchymal interactions: insights into physiological and pathological aspects of oral tissues.

PubMed

Santosh, Arvind Babu Rajendra; Jones, Thaon Jon

2014-03-17

In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs) are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer.

Engineering muscle cell alignment through 3D bioprinting.

PubMed

Mozetic, Pamela; Giannitelli, Sara Maria; Gori, Manuele; Trombetta, Marcella; Rainer, Alberto

2017-09-01

Processing of hydrogels represents a main challenge for the prospective application of additive manufacturing (AM) to soft tissue engineering. Furthermore, direct manufacturing of tissue precursors with a cell density similar to native tissues has the potential to overcome the extensive in vitro culture required for conventional cell-seeded scaffolds seeking to fabricate constructs with tailored structural and functional properties. In this work, we present a simple AM methodology that exploits the thermoresponsive behavior of a block copolymer (Pluronic ® ) as a means to obtain good shape retention at physiological conditions and to induce cellular alignment. Pluronic/alginate blends have been investigated as a model system for the processing of C2C12 murine myoblast cell line. Interestingly, C2C12 cell model demonstrated cell alignment along the deposition direction, potentially representing a new avenue to tailor the resulting cell histoarchitecture during AM process. Furthermore, the fabricated constructs exhibited high cell viability, as well as a significantly improved expression of myogenic genes vs. conventional 2D cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2582-2588, 2017. © 2017 Wiley Periodicals, Inc.

Evolutionary process development towards next generation crystalline silicon solar cells : a semiconductor process toolbox application

NASA Astrophysics Data System (ADS)

John, J.; Prajapati, V.; Vermang, B.; Lorenz, A.; Allebe, C.; Rothschild, A.; Tous, L.; Uruena, A.; Baert, K.; Poortmans, J.

2012-08-01

Bulk crystalline Silicon solar cells are covering more than 85% of the world's roof top module installation in 2010. With a growth rate of over 30% in the last 10 years this technology remains the working horse of solar cell industry. The full Aluminum back-side field (Al BSF) technology has been developed in the 90's and provides a production learning curve on module price of constant 20% in average. The main reason for the decrease of module prices with increasing production capacity is due to the effect of up scaling industrial production. For further decreasing of the price per wattpeak silicon consumption has to be reduced and efficiency has to be improved. In this paper we describe a successive efficiency improving process development starting from the existing full Al BSF cell concept. We propose an evolutionary development includes all parts of the solar cell process: optical enhancement (texturing, polishing, anti-reflection coating), junction formation and contacting. Novel processes are benchmarked on industrial like baseline flows using high-efficiency cell concepts like i-PERC (Passivated Emitter and Rear Cell). While the full Al BSF crystalline silicon solar cell technology provides efficiencies of up to 18% (on cz-Si) in production, we are achieving up to 19.4% conversion efficiency for industrial fabricated, large area solar cells with copper based front side metallization and local Al BSF applying the semiconductor toolbox.

Multimodal quantitative phase and fluorescence imaging of cell apoptosis

NASA Astrophysics Data System (ADS)

Fu, Xinye; Zuo, Chao; Yan, Hao

2017-06-01

Fluorescence microscopy, utilizing fluorescence labeling, has the capability to observe intercellular changes which transmitted and reflected light microscopy techniques cannot resolve. However, the parts without fluorescence labeling are not imaged. Hence, the processes simultaneously happen in these parts cannot be revealed. Meanwhile, fluorescence imaging is 2D imaging where information in the depth is missing. Therefore the information in labeling parts is also not complete. On the other hand, quantitative phase imaging is capable to image cells in 3D in real time through phase calculation. However, its resolution is limited by the optical diffraction and cannot observe intercellular changes below 200 nanometers. In this work, fluorescence imaging and quantitative phase imaging are combined to build a multimodal imaging system. Such system has the capability to simultaneously observe the detailed intercellular phenomenon and 3D cell morphology. In this study the proposed multimodal imaging system is used to observe the cell behavior in the cell apoptosis. The aim is to highlight the limitations of fluorescence microscopy and to point out the advantages of multimodal quantitative phase and fluorescence imaging. The proposed multimodal quantitative phase imaging could be further applied in cell related biomedical research, such as tumor.

Regulated Forms of Cell Death in Fungi

PubMed Central

Gonçalves, A. Pedro; Heller, Jens; Daskalov, Asen; Videira, Arnaldo; Glass, N. Louise

2017-01-01

Cell death occurs in all domains of life. While some cells die in an uncontrolled way due to exposure to external cues, other cells die in a regulated manner as part of a genetically encoded developmental program. Like other eukaryotic species, fungi undergo programmed cell death (PCD) in response to various triggers. For example, exposure to external stress conditions can activate PCD pathways in fungi. Calcium redistribution between the extracellular space, the cytoplasm and intracellular storage organelles appears to be pivotal for this kind of cell death. PCD is also part of the fungal life cycle, in which it occurs during sexual and asexual reproduction, aging, and as part of development associated with infection in phytopathogenic fungi. Additionally, a fungal non-self-recognition mechanism termed heterokaryon incompatibility (HI) also involves PCD. Some of the molecular players mediating PCD during HI show remarkable similarities to major constituents involved in innate immunity in metazoans and plants. In this review we discuss recent research on fungal PCD mechanisms in comparison to more characterized mechanisms in metazoans. We highlight the role of PCD in fungi in response to exogenic compounds, fungal development and non-self-recognition processes and discuss identified intracellular signaling pathways and molecules that regulate fungal PCD. PMID:28983298

Cell Migration

PubMed Central

Trepat, Xavier; Chen, Zaozao; Jacobson, Ken

2015-01-01

Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large-scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single-cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis. PMID:23720251

Metabolic Stress and Compromised Identity of Pancreatic Beta Cells

PubMed Central

Swisa, Avital; Glaser, Benjamin; Dor, Yuval

2017-01-01

Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D. PMID:28270834

Metabolic Stress and Compromised Identity of Pancreatic Beta Cells.

PubMed

Swisa, Avital; Glaser, Benjamin; Dor, Yuval

2017-01-01

Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D.

Impact of genomic damage and ageing on stem cell function

PubMed Central

Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

2014-01-01

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

Tissue Architecture and Microenvironment Sustain Hormone Signaling | Center for Cancer Research

Cancer.gov

Cells interact with their environments in part through protein receptors embedded in the cell membrane. Activation of a receptor by external signaling molecules sets off a complex chain of events within the cell that can result in alterations in protein structure and function and/or changes in gene expression. Proper integration of these signals is crucial for normal cell growth and development. A more complete understanding of these normal processes will help elucidate how aberrant signaling results in diseases such as cancer.  

Leucine Promotes Proliferation and Differentiation of Primary Preterm Rat Satellite Cells in Part through mTORC1 Signaling Pathway

PubMed Central

Dai, Jie-Min; Yu, Mu-Xue; Shen, Zhen-Yu; Guo, Chu-Yi; Zhuang, Si-Qi; Qiu, Xiao-Shan

2015-01-01

Signaling through the mammalian target of rapamycin (mTOR) in response to leucine modulates many cellular and developmental processes. However, in the context of satellite cell proliferation and differentiation, the role of leucine and mTORC1 is less known. This study investigates the role of leucine in the process of proliferation and differentiation of primary preterm rat satellite cells, and the relationship with mammalian target of rapamycin complex 1 (mTORC1) activation. Dissociation of primary satellite cells occurred with type I collagenase and trypsin, and purification, via different speed adherence methods. Satellite cells with positive expression of Desmin were treated with leucine and rapamycin. We observed that leucine promoted proliferation and differentiation of primary satellite cells and increased the phosphorylation of mTOR. Rapamycin inhibited proliferation and differentiation, as well as decreased the phosphorylation level of mTOR. Furthermore, leucine increased the expression of MyoD and myogenin while the protein level of MyoD decreased due to rapamycin. However, myogenin expressed no affect by rapamycin. In conclusion, leucine may up-regulate the activation of mTORC1 to promote proliferation and differentiation of primary preterm rat satellite cells. We have shown that leucine promoted the differentiation of myotubes in part through the mTORC1-MyoD signal pathway. PMID:26007333

PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

EPA Science Inventory

New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

KSC-2011-8286

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians assist as a special crane is used to lift one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8283

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as a special crane lifts one of the three fuel cells away from space shuttle Atlantis’ for securing on a special platform. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8284

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians assist as a special crane is used to lift one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8285

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians assist as a special crane is used to lift one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8287

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as a special crane lifts one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8279

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, a technician assists as a special crane lifts one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8278

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as a special crane lifts one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8288

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, a technician assists as a special crane is used to lift one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8282

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as a special crane lifts one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

KSC-2011-8281

NASA Image and Video Library

2011-12-13

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA’s Kennedy Space Center in Florida, technicians help position a special crane in place to lift one of the three fuel cells away from space shuttle Atlantis’ payload bay. The fuel cells will be drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Atlantis’ mid-body and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Atlantis. The orbiter is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Kim Shiflett

1-Nitropyrene (1-NP) induces apoptosis and apparently a non-apoptotic programmed cell death (paraptosis) in Hepa1c1c7 cells

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

Asare, Nana; Landvik, Nina E.; Lagadic-Gossmann, Dominique

2008-07-15

Mechanistic studies of nitro-PAHs (polycyclic aromatic hydrocarbons) of interest might help elucidate which chemical characteristics are most important in eliciting toxic effects. 1-Nitropyrene (1-NP) is the predominant nitrated PAH emitted in diesel exhaust. 1-NP-exposed Hepa1c1c7 cells exhibited marked changes in cellular morphology, decreased proliferation and different forms of cell death. A dramatic increase in cytoplasmic vacuolization was observed already after 6 h of exposure and the cells started to round up at 12 h. The rate of cell proliferation was markedly reduced at 24 h and apoptotic as well as propidium iodide (PI)-positive cells appeared. Electron microscopic examination revealed thatmore » the vacuolization was partly due to mitochondria swelling. The caspase inhibitor Z-VAD-FMK inhibited only the apoptotic cell death and Nec-1 (an inhibitor of necroptosis) exhibited no inhibitory effects on either cell death or vacuolization. In contrast, cycloheximide markedly reduced both the number of apoptotic and PI-positive cells as well as the cytoplasmic vacuolization, suggesting that 1-NP induced paraptotic cell death. All the MAPKs; ERK1/2, p38 and JNK, appear to be involved in the death process since marked activation was observed upon 1-NP exposure, and their inhibitors partly reduced the induced cell death. The ERK1/2 inhibitor PD 98057 completely blocked the induced vacuolization, whereas the other MAPKs inhibitors only had minor effects on this process. These findings suggest that 1-NP may cause apoptosis and paraptosis. In contrast, the corresponding amine (1-aminopyrene) elicited only minor apoptotic and necrotic cell death, and cells with characteristics typical of paraptosis were absent.« less

Association to HeLa cells and surface behavior of exogenous gangliosides studied with a fluorescent derivative of GM1

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

Masserini, M.; Giuliani, A.; Palestini, P.

1990-01-23

Cultured HeLa cells were incubated with pyrene-GM1/{sup 3}H-radiolabeled GM1 ganglioside (1:4 M/M) mixtures for various times. The process of association of pyrene-GM1 with cells was qualitatively and quantitatively the same as that of {sup 3}H-GM1. The pyrene-GM1 and {sup 3}H-GM1 proportions in the various forms of association with cells were similar to that of the starting ganglioside mixture. After 2-h incubation, the association of ganglioside with cells was well established whereas almost no metabolic processing had occurred. During a 24-h incubation, pyrene- and {sup 3}H-GM1 underwent similar metabolic processing and gave rise to catabolic (GM2 and GM3) and anabolic (GDla)more » derivatives. Fluorescence spectroscopy experiments carried out with the excimer formation technique on subcellular fractions containing plasma membranes showed that exogenous ganglioside was, in part, associated with the cells in a micellar form removable by trypsin treatment, and in part inserted in a seemingly molecular dispersion. Addition of Ca{sup 2+} salts caused aggregation of the ganglioside, as indicated by the increase of the excimer:monomer fluorescence ratio. The phenomenon was Ca{sup 2+} concentration dependent (maximum at 10 mM), and subsequent addition of EDTA has no effect. The saccharide portion of exogenously incorporated pyrene-GM1 was available to interact with external ligands, as shown by its ability to bind cholera toxin whose addition reduced the collision rate among the ganglioside lipid moieties.« less

Numerical simulation of multi-layered textile composite reinforcement forming

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

Wang, P.; Hamila, N.; Boisse, P.

2011-05-04

One important perspective in aeronautics is to produce large, thick or/and complex structural composite parts. The forming stage presents an important role during the whole manufacturing process, especially for LCM processes (Liquid Composites Moulding) or CFRTP (Continuous Fibre Reinforcements and Thermoplastic resin). Numerical simulations corresponding to multi-layered composite forming allow the prediction for a successful process to produce the thick parts, and importantly, the positions of the fibres after forming to be known. This paper details a set of simulation examples carried out by using a semi-discrete shell finite element made up of unit woven cells. The internal virtual workmore » is applied on all woven cells of the element taking into account tensions, in-plane shear and bending effects. As one key problem, the contact behaviours of tool/ply and ply/ply are described in the numerical model. The simulation results not only improve our understanding of the multi-layered composite forming process but also point out the importance of the fibre orientation and inter-ply friction during formability.« less

Thermosetting Fluoropolymer Foams

NASA Technical Reports Server (NTRS)

Lee, Sheng Yen

1987-01-01

New process makes fluoropolymer foams with controllable amounts of inert-gas fillings in foam cells. Thermosetting fluoropolymers do not require foaming additives leaving undesirable residues and do not have to be molded and sintered at temperatures of about 240 to 400 degree C. Consequently, better for use with electronic or other parts sensitive to high temperatures or residues. Uses include coatings, electrical insulation, and structural parts.

Riedel's thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum.

PubMed

Dahlgren, Mollie; Khosroshahi, Arezou; Nielsen, G Petur; Deshpande, Vikram; Stone, John H

2010-09-01

Riedel's thyroiditis is a chronic fibrosing disorder of unknown etiology often associated with "multifocal fibrosclerosis." IgG4-related systemic disease is characterized by IgG4+ plasma cell infiltration and fibrosis throughout many organs. We hypothesized that Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. We searched our institution's pathology database using the terms "Riedel's," "struma," "thyroid," and "fibrosis," and identified 3 cases of Riedel's thyroiditis. Riedel's thyroiditis was diagnosed if there was a fibroinflammatory process involving all or a portion of the thyroid gland, with evidence of extension of the process into surrounding tissues. Immunohistochemical stains for IgG4 and IgG were performed. The histopathologic and immunohistochemical features of each involved organ were evaluated. The clinical features of one patient with multiple organ system disease were described. All 3 thyroidectomy samples stained positively for IgG4-bearing plasma cells. One patient had extensive extrathyroidal involvement diagnostic of IgG4-related systemic disease, including cholangitis, pseudotumors of both the lung and lacrimal gland, and a lymph node contiguous to the thyroid that stained intensely for IgG4+ plasma cells. The histologic features of all organs involved were consistent with IgG4-related systemic disease. Patient 3 had 10 IgG4+ plasma cells per high-power field initially, but rebiopsy 2 years later demonstrated no IgG4+ plasma cells. That patient's second biopsy, characterized by fibrosis and minimal residual inflammation, further solidifies the link between IgG4-bearing plasma cells in tissue and the histologic evolution to Riedel's thyroiditis. Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. In many cases, multifocal fibrosclerosis and IgG4-related systemic disease are probably the same entity.

XTH20 and XTH19 regulated by ANAC071 under auxin flow are involved in cell proliferation in incised Arabidopsis inflorescence stems.

PubMed

Pitaksaringkarn, Weerasak; Matsuoka, Keita; Asahina, Masashi; Miura, Kenji; Sage-Ono, Kimiyo; Ono, Michiyuki; Yokoyama, Ryusuke; Nishitani, Kazuhiko; Ishii, Tadashi; Iwai, Hiroaki; Satoh, Shinobu

2014-11-01

One week after partial incision of Arabidopsis inflorescence stems, the repair process in damaged tissue includes pith cell proliferation. Auxin is a key factor driving this process, and ANAC071, a transcription factor gene, is upregulated in the distal region of the incised stem. Here we show that XTH20 and the closely related XTH19, members of xyloglucan endotransglucosylase/hydrolases family catalyzing molecular grafting and/or hydrolysis of cell wall xyloglucans, were also upregulated in the distal part of the incised stem, similar to ANAC071. XTH19 was expressed in the proximal incision region after 3 days or after auxin application to the decapitated stem. Horizontal positioning of the plant with the incised side up resulted in decreased ProDR 5 :GUS, ANAC071, XTH20, and XTH19 expression and reduced pith cell proliferation. In incised stems of Pro35S :ANAC071-SRDX plants, expression of XTH20 and XTH19 was substantially and moderately decreased, respectively. XTH20 and XTH19 expression and pith cell proliferation were suppressed in anac071 plants and were increased in Pro35S :ANAC071 plants. Pith cell proliferation was also inhibited in the xth20xth19 double mutant. Furthermore, ANAC071 bound to the XTH20 and XTH19 promoters to induce their expression. This study revealed XTH20 and XTH19 induction by auxin via ANAC071 in the distal part of an incised stem and their involvement in cell proliferation in the tissue reunion process. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

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

Huang, Yuan; Luo, Fangjun; Li, Hui

During inflammation in the glomerulus, the proliferation of myofiroblast-like mesangial cells is commonly associated with the pathological process. Macrophages play an important role in regulating the growth of resident mesangial cells in the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of macrophages induced by IL-13/IL-4, which is shown to play a repair role in glomerulonephritis. Prompted by studies of development, we performed bone marrow derived macrophage and rat mesangial cell co-culture study. Conditioned medium from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro-apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained with Hoechstmore » 33258, increased apoptosis rates by flow cytometry analysis and enhanced caspase-3 activation by western blot. Fas protein was up-regulated in rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2 macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2 macrophage also contributed to this apoptotic effect. These results indicated that the process of apoptosis triggered by conditioned medium from M2 macrophages, at least is partly conducted through Fas in rat mesangial cells. Our findings provide compelling evidence that M2 macrophages control the growth of mesangial cells in renal inflammatory conditions. - Highlights: • Conditioned-medium from M2 macrophages induces rat mesangial cell (MsC) apoptosis. • M2 macrophage conditioned medium exerts its pro-apoptotic effects via Fas ligand. • Arginase-1 activity in M2 macrophages plays a role in inducing apoptosis in rat MsC.« less

Ingression-type cell migration drives vegetal endoderm internalisation in the Xenopus gastrula

PubMed Central

Wen, Jason WH

2017-01-01

During amphibian gastrulation, presumptive endoderm is internalised as part of vegetal rotation, a large-scale movement that encompasses the whole vegetal half of the embryo. It has been considered a gastrulation process unique to amphibians, but we show that at the cell level, endoderm internalisation exhibits characteristics reminiscent of bottle cell formation and ingression, known mechanisms of germ layer internalisation. During ingression proper, cells leave a single-layered epithelium. In vegetal rotation, the process occurs in a multilayered cell mass; we refer to it as ingression-type cell migration. Endoderm cells move by amoeboid shape changes, but in contrast to other instances of amoeboid migration, trailing edge retraction involves ephrinB1-dependent macropinocytosis and trans-endocytosis. Moreover, although cells are separated by wide gaps, they are connected by filiform protrusions, and their migration depends on C-cadherin and the matrix protein fibronectin. Cells move in the same direction but at different velocities, to rearrange by differential migration. PMID:28826499

Multiplexing a high-throughput liability assay to leverage efficiencies.

PubMed

Herbst, John; Anthony, Monique; Stewart, Jeremy; Connors, David; Chen, Taosheng; Banks, Martyn; Petrillo, Edward W; Agler, Michele

2009-06-01

In order to identify potential cytochrome P-450 3A4 (drug-metabolizing enzyme) inducers at an early stage of the drug discovery process, a cell-based transactivation high-throughput luciferase reporter assay for the human pregnane X receptor (PXR) in HepG2 cells has been implemented and multiplexed with a viability end point for data interpretation, as part of a Lead Profiling portfolio of assays. As a routine part of Lead Profiling operations, assays are periodically evaluated for utility as well as for potential improvements in technology or process. We used a recent evaluation of our PXR-transactivation assay as a model for the application of Lean Thinking-based process analysis to lab-bench assay optimization and automation. This resulted in the development of a 384-well multiplexed homogeneous assay simultaneously detecting PXR transactivation and HepG2 cell cytotoxicity. In order to multiplex fluorescent and luminescent read-outs, modifications to each assay were necessary, which included optimization of multiple assay parameters such as cell density, plate type, and reagent concentrations. Subsequently, a set of compounds including known cytotoxic compounds and PXR inducers were used to validate the multiplexed assay. Results from the multiplexed assay correlate well with those from the singleplexed assay formats measuring PXR transactivation and viability separately. Implementation of the multiplexed assay for routine compound profiling provides improved data quality, sample conservation, cost savings, and resource efficiencies.

Chronicle of a pigmented superficial Basal cell carcinoma.

PubMed

Caucanas, Marie; Piérard-Franchimont, Claudine; Piérard, Gérald E

2012-01-01

Dermoscopic patterns of basal cell carcinoma (BCC) are well defined, but the dynamics of dermoscopic changes in time were apparently never described so far. In this paper, prominent changes were observed over a 8-week period, allowing to establish a close connection between spoke wheel areas and maple leaf-like aspects, through progressive thickening of the former ones. A chronobiological phenomenon ruling synchronous apoptosis in some of the most superficial BCC nests is suggested, leading to a wax and wane process of millimetric crusts, taking part in the spontaneous BCC regression/progression process.

Image processing and machine learning in the morphological analysis of blood cells.

PubMed

Rodellar, J; Alférez, S; Acevedo, A; Molina, A; Merino, A

2018-05-01

This review focuses on how image processing and machine learning can be useful for the morphological characterization and automatic recognition of cell images captured from peripheral blood smears. The basics of the 3 core elements (segmentation, quantitative features, and classification) are outlined, and recent literature is discussed. Although red blood cells are a significant part of this context, this study focuses on malignant lymphoid cells and blast cells. There is no doubt that these technologies may help the cytologist to perform efficient, objective, and fast morphological analysis of blood cells. They may also help in the interpretation of some morphological features and may serve as learning and survey tools. Although research is still needed, it is important to define screening strategies to exploit the potential of image-based automatic recognition systems integrated in the daily routine of laboratories along with other analysis methodologies. © 2018 John Wiley & Sons Ltd.

Calcium carbonate mineralization mediated by in vitro cultured mantle cells from Pinctada fucata.

PubMed

Kong, Wei; Li, Shiguo; Xiang, Liang; Xie, Liping; Zhang, Rongqing

2015-08-07

Formation of the molluscan shell is believed to be an extracellular event mediated by matrix proteins. We report calcium carbonate mineralization mediated by Pinctada fucata mantle cells. Crystals only appeared when mantle cells were present in the crystallization solution. These crystals were piled up in highly ordered units and showed the typical characteristics of biomineralization products. A thin organic framework was observed after dissolving the crystals in EDTA. Some crystals had etched surfaces with a much smoother appearance than other parts. Mantle cells were observed to be attached to some of these smooth surfaces. These results suggest that mantle cells may be directly involved in the nucleation and remodeling process of calcium carbonate mineralization. Our result demonstrate the practicability of studying the mantle cell mechanism of biomineralization and contribute to the overall understanding of the shell formation process. Copyright © 2015 Elsevier Inc. All rights reserved.

Tight Junction Protein 1a regulates pigment cell organisation during zebrafish colour patterning.

PubMed

Fadeev, Andrey; Krauss, Jana; Frohnhöfer, Hans Georg; Irion, Uwe; Nüsslein-Volhard, Christiane

2015-04-27

Zebrafish display a prominent pattern of alternating dark and light stripes generated by the precise positioning of pigment cells in the skin. This arrangement is the result of coordinated cell movements, cell shape changes, and the organisation of pigment cells during metamorphosis. Iridophores play a crucial part in this process by switching between the dense form of the light stripes and the loose form of the dark stripes. Adult schachbrett (sbr) mutants exhibit delayed changes in iridophore shape and organisation caused by truncations in Tight Junction Protein 1a (ZO-1a). In sbr mutants, the dark stripes are interrupted by dense iridophores invading as coherent sheets. Immuno-labelling and chimeric analyses indicate that Tjp1a is expressed in dense iridophores but down-regulated in the loose form. Tjp1a is a novel regulator of cell shape changes during colour pattern formation and the first cytoplasmic protein implicated in this process.

Clinical trial tests drug for tumors associated with Krebs-cycle dysfunction | Center for Cancer Research

Cancer.gov

The Krebs cycle is part of the complex process where cells turn food into energy. One of the elements of the Krebs cycle is succinate dehydrogenase (SDH). Loss of SDH activity in cells has been linked to tumor formation. This new trial is studying guadecitabine for tumors associated with Krebs cycle dysfunction. Learn more...

Understanding of Protein Synthesis in a Living Cell

ERIC Educational Resources Information Center

Mustapha, Y.; Muhammad, S.

2006-01-01

The assembly of proteins takes place in the cytoplasm of a cell. There are three main steps. In initiation, far left, all the necessary parts of the process are brought together by a small molecule called a ribosome. During elongation, amino acids, the building blocks of proteins, are joined to one another in a long chain. The sequence in which…

Active cell mechanics: Measurement and theory.

PubMed

Ahmed, Wylie W; Fodor, Étienne; Betz, Timo

2015-11-01

Living cells are active mechanical systems that are able to generate forces. Their structure and shape are primarily determined by biopolymer filaments and molecular motors that form the cytoskeleton. Active force generation requires constant consumption of energy to maintain the nonequilibrium activity to drive organization and transport processes necessary for their function. To understand this activity it is necessary to develop new approaches to probe the underlying physical processes. Active cell mechanics incorporates active molecular-scale force generation into the traditional framework of mechanics of materials. This review highlights recent experimental and theoretical developments towards understanding active cell mechanics. We focus primarily on intracellular mechanical measurements and theoretical advances utilizing the Langevin framework. These developing approaches allow a quantitative understanding of nonequilibrium mechanical activity in living cells. This article is part of a Special Issue entitled: Mechanobiology. Copyright © 2015. Published by Elsevier B.V.

Antigen recognition in the islets changes with progression of autoimmune islet infiltration

PubMed Central

Lindsay, Robin S.; Corbin, Kaitlin; Mahne, Ashley; Levitt, Bonnie E.; Gebert, Matthew J.; Wigton, Eric J.; Bradley, Brenda J.; Haskins, Kathryn; Jacobelli, Jordan; Tang, Qizhi; Krummel, Matthew F.; Friedman, Rachel S.

2014-01-01

In type 1 diabetes, the pancreatic islets are an important site for therapeutic intervention since immune infiltration of the islets is well established at diagnosis. Therefore, understanding the events that underlie the continued progression of the autoimmune response and islet destruction is critical. Islet infiltration and destruction is an asynchronous process, making it important to analyze the disease process on a single islet basis. To understand how T cell stimulation evolves through the process of islet infiltration we analyzed the dynamics of T cell movement and interactions within individual islets of spontaneously autoimmune non-obese diabetic (NOD) mice. Using both intra-vital and explanted 2-photon islet imaging, we defined a correlation between increased islet infiltration and increased T cell motility. Early T cell arrest was antigen dependent and due, at least in part, to antigen recognition through sustained interactions with CD11c+ antigen presenting cells (APCs). As islet infiltration progressed, T cell motility became antigen-independent, with a loss of T cell arrest and sustained interactions with CD11c+ APCs. These studies suggest that the autoimmune T cell response in the islets may be temporarily dampened during the course of islet infiltration and disease progression. PMID:25505281

The expression and function of cathepsin E in dendritic cells.

PubMed

Chain, Benjamin M; Free, Paul; Medd, Patrick; Swetman, Claire; Tabor, Alethea B; Terrazzini, Nadia

2005-02-15

Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class II MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class II MHC Ag processing pathway within dendritic cells.

Lasers in energy device manufacturing

NASA Astrophysics Data System (ADS)

Ostendorf, A.; Schoonderbeek, A.

2008-02-01

Global warming is a current topic all over the world. CO II emissions must be lowered to stop the already started climate change. Developing regenerative energy sources, like photovoltaics and fuel cells contributes to the solution of this problem. Innovative technologies and strategies need to be competitive with conventional energy sources. During the last years, the photovoltaic solar cell industry has experienced enormous growth. However, for solar cells to be competitive on the longer term, both an increase in efficiency as well as reduction in costs is necessary. An effective method to reduce costs of silicon solar cells is reducing the wafer thickness, because silicon makes up a large part of production costs. Consequently, contact free laser processing has a large advantage, because of the decrease in waste materials due to broken wafers as caused by other manufacturing processes. Additionally, many novel high efficiency solar cell concepts are only economically feasible with laser technology, e.g. for scribing silicon thin-film solar cells. This paper describes laser hole drilling, structuring and texturing of silicon wafer based solar cells and describes thin film solar cell scribing. Furthermore, different types of lasers are discussed with respect to processing quality and time.

KSC-2011-8204

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

KSC-2011-8203

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

Photonic crystal geometry for organic solar cells.

PubMed

Ko, Doo-Hyun; Tumbleston, John R; Zhang, Lei; Williams, Stuart; DeSimone, Joseph M; Lopez, Rene; Samulski, Edward T

2009-07-01

We report organic solar cells with a photonic crystal nanostructure embossed in the photoactive bulk heterojunction layer, a topography that exhibits a 3-fold enhancement of the absorption in specific regions of the solar spectrum in part through multiple excitation resonances. The photonic crystal geometry is fabricated using a materials-agnostic process called PRINT wherein highly ordered arrays of nanoscale features are readily made in a single processing step over wide areas (approximately 4 cm(2)) that is scalable. We show efficiency improvements of approximately 70% that result not only from greater absorption, but also from electrical enhancements. The methodology is generally applicable to organic solar cells and the experimental findings reported in our manuscript corroborate theoretical expectations.

Downregulation of Pink1 influences mitochondrial fusion–fission machinery and sensitizes to neurotoxins in dopaminergic cells

PubMed Central

Rojas-Charry, Liliana; Cookson, Mark R.; Niño, Andrea; Arboleda, Humberto; Arboleda, Gonzalo

2016-01-01

It is now well established that mitochondria are organelles that, far from being static, are subject to a constant process of change. This process, which has been called mitochondrial dynamics, includes processes of both fusion and fission. Loss of Pink1 (PTEN-induced putative kinase 1) function is associated with early onset recessive Parkinson’s disease and it has been proposed that mitochondrial dynamics might be affected by loss of the mitochondrial kinase. Here, we report the effects of silencing Pink1 on mitochondrial fusion and fission events in dopaminergic neuron cell lines. Cells lacking Pink1 were more sensitive to cell death induced by C2-Ceramide, which inhibits proliferation and induces apoptosis. In the same cell lines, mitochondrial morphology was fragmented and this was enhanced by application of forskolin, which stimulates the cAMP pathway that phosphorylates Drp1 and thereby inactivates it. Cells lacking Pink1 had lower Drp1 and Mfn2 expression. Based on these data, we propose that Pink1 may exert a neuroprotective role in part by limiting mitochondrial fission. PMID:24792327

The Dendritic Cell Major Histocompatibility Complex II (MHC II) Peptidome Derives from a Variety of Processing Pathways and Includes Peptides with a Broad Spectrum of HLA-DM Sensitivity*

PubMed Central

Clement, Cristina C.; Becerra, Aniuska; Yin, Liusong; Zolla, Valerio; Huang, Liling; Merlin, Simone; Follenzi, Antonia; Shaffer, Scott A.; Stern, Lawrence J.; Santambrogio, Laura

2016-01-01

The repertoire of peptides displayed in vivo by MHC II molecules derives from a wide spectrum of proteins produced by different cell types. Although intracellular endosomal processing in dendritic cells and B cells has been characterized for a few antigens, the overall range of processing pathways responsible for generating the MHC II peptidome are currently unclear. To determine the contribution of non-endosomal processing pathways, we eluted and sequenced over 3000 HLA-DR1-bound peptides presented in vivo by dendritic cells. The processing enzymes were identified by reference to a database of experimentally determined cleavage sites and experimentally validated for four epitopes derived from complement 3, collagen II, thymosin β4, and gelsolin. We determined that self-antigens processed by tissue-specific proteases, including complement, matrix metalloproteases, caspases, and granzymes, and carried by lymph, contribute significantly to the MHC II self-peptidome presented by conventional dendritic cells in vivo. Additionally, the presented peptides exhibited a wide spectrum of binding affinity and HLA-DM susceptibility. The results indicate that the HLA-DR1-restricted self-peptidome presented under physiological conditions derives from a variety of processing pathways. Non-endosomal processing enzymes add to the number of epitopes cleaved by cathepsins, altogether generating a wider peptide repertoire. Taken together with HLA-DM-dependent and-independent loading pathways, this ensures that a broad self-peptidome is presented by dendritic cells. This work brings attention to the role of “self-recognition” as a dynamic interaction between dendritic cells and the metabolic/catabolic activities ongoing in every parenchymal organ as part of tissue growth, remodeling, and physiological apoptosis. PMID:26740625

Efficient Solar Concentrators: Affordable Energy from Water and Sunlight

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

None

2010-01-01

Broad Funding Opportunity Announcement Project: Teledyne is developing a liquid prism panel that tracks the position of the sun to help efficiently concentrate its light onto a solar cell to produce power. Typically, solar tracking devices have bulky and expensive mechanical moving parts that require a lot of power and are often unreliable. Teledyne’s liquid prism panel has no bulky and heavy supporting parts—instead it relies on electrowetting. Electrowetting is a process where an electric field is applied to the liquid to control the angle at which it meets the sunlight above and to control the angle of the sunlightmore » to the focusing lensthe more direct the angle to the focusing lens, the more efficiently the light can be concentrated to solar panels and converted into electricity. This allows the prism to be tuned like a radio to track the sun across the sky and steer sunlight into the solar cell without any moving mechanical parts. This process uses very little power and requires no expensive supporting hardware or moving parts, enabling efficient and quiet rooftop operation for integration into buildings.« less

Only in dying, life: programmed cell death during plant development.

PubMed

Van Hautegem, Tom; Waters, Andrew J; Goodrich, Justin; Nowack, Moritz K

2015-02-01

Programmed cell death (PCD) is a fundamental process of life. During the evolution of multicellular organisms, the actively controlled demise of cells has been recruited to fulfil a multitude of functions in development, differentiation, tissue homeostasis, and immune systems. In this review we discuss some of the multiple cases of PCD that occur as integral parts of plant development in a remarkable variety of cell types, tissues, and organs. Although research in the last decade has discovered a number of PCD regulators, mediators, and executers, we are still only beginning to understand the mechanistic complexity that tightly controls preparation, initiation, and execution of PCD as a process that is indispensable for successful vegetative and reproductive development of plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Symmetrization in jellyfish: reorganization to regain function, and not lost parts.

PubMed

Abrams, Michael J; Goentoro, Lea

2016-02-01

We recently reported a previously unidentified strategy of self-repair in the moon jellyfish Aurelia aurita. Rather than regenerating lost parts, juvenile Aurelia reorganize remaining parts to regain essential body symmetry. This process that we called symmetrization is rapid and frequent, and is not driven by cell proliferation or cell death. Instead, the swimming machinery generates mechanical forces that drive symmetrization. We found evidence for symmetrization across three other species of jellyfish (Chrysaora pacifica, Mastigias sp., and Cotylorhiza tuberculata). We propose reorganization to regain function without recovery of initial morphology as a potentially broad class of self-repair strategy beyond radially symmetrical animals, and discuss the implications of this finding on the evolution of self-repair strategies in animals. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Usher syndrome: molecular links of pathogenesis, proteins and pathways.

PubMed

Kremer, Hannie; van Wijk, Erwin; Märker, Tina; Wolfrum, Uwe; Roepman, Ronald

2006-10-15

Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear and in photoreceptor cells of the retina. The localization of the Usher proteins and the phenotype in animal models indicate that the Usher protein complex is essential in the morphogenesis of the stereocilia bundle in hair cells and in the calycal processes of photoreceptor cells. In addition, the Usher proteins are important in the synaptic processes of both cell types. The association of other proteins with the complex indicates functional links to a number of basic cell-biological processes. Prominently present is the connection to the dynamics of the actin cytoskeleton, involved in cellular morphology, cell polarity and cell-cell interactions. The Usher protein complex can also be linked to the cadherins/catenins in the adherens junction-associated protein complexes, suggesting a role in cell polarity and tissue organization. A third link can be established to the integrin transmembrane signaling network. The Usher interactome, as outlined in this review, participates in pathways common in inner ear and retina that are disrupted in the Usher syndrome.

Automated thematic mapping and change detection of ERTS-A images

NASA Technical Reports Server (NTRS)

Gramenopoulos, N. (Principal Investigator)

1975-01-01

The author has identified the following significant results. In the first part of the investigation, spatial and spectral features were developed which were employed to automatically recognize terrain features through a clustering algorithm. In this part of the investigation, the size of the cell which is the number of digital picture elements used for computing the spatial and spectral features was varied. It was determined that the accuracy of terrain recognition decreases slowly as the cell size is reduced and coincides with increased cluster diffuseness. It was also proven that a cell size of 17 x 17 pixels when used with the clustering algorithm results in high recognition rates for major terrain classes. ERTS-1 data from five diverse geographic regions of the United States were processed through the clustering algorithm with 17 x 17 pixel cells. Simple land use maps were produced and the average terrain recognition accuracy was 82 percent.

Excimer laser interaction with dentin of the human tooth

NASA Technical Reports Server (NTRS)

Hammond, Ernest C., Jr.; Gilliam, Ruth L.; Baker, George R.

1989-01-01

The use an excimer laser produced many unusual conical structures within the dentin of the inner part of the human tooth. By varying the frequency of the laser one can disperse the energy and cause more bleeding in laser surgery, but not destroy the cells associated with the incision. Therefore, the healing process will virtually be without scarring. Whereas, using the infrared laser the blood loss would be less, but the healing process would tend to be longer because cells are being destroyed due to the cauterization effect of the laser. The question is, are these structures produced as an interaction with the laser or are they an intrinsic part of the structure. The effects of the laser interaction upon dentin was studied, and in using electron microscopy the interaction of the excimer laser upon the tooth dentin and other various biological tissue is more clearly understood.

Chirality of the cytoskeleton in the origins of cellular asymmetry

PubMed Central

2016-01-01

Self-assembly of two important components of the cytoskeleton of eukaryotic cells, actin microfilaments and microtubules (MTs) results in polar filaments of one chirality. As is true for bacterial flagella, in actin microfilaments, screw direction is important for assembly processes and motility. For MTs, polar orientation within the cell is paramount. The alignment of these elements in the cell cytoplasm gives rise to emergent properties, including the potential for cell differentiation and specialization. Complex MTs with a characteristic chirality are found in basal bodies and centrioles; this chirality is preserved in cilia. In motile cilia, it is reflected in the direction of the effective stroke. The positioning of the basal body or cilia on the cell surface depends on polarity proteins. In evolution, survival depends on global polarity information relayed to the cell in part by orientation of the MT and actin filament cytoskeletons and the chirality of the basal body to determine left and right coordinates within a defined anterior–posterior cell and tissue axis. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821520

Xeroderma pigmentosum complementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes

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

Venema, J.; van Hoffen, A.; Karcagi, V.

1991-08-01

The authors have measured the removal of UV-induced pyrimidine dimers from DNA fragments of the adenosine deaminase (ADA) and dihydrofolate reductase (DHFR) genes in primary normal human and xeroderma pigmentosum complementation group C (XP-C) cells. Using strand-specific probes, we show that in normal cells, preferential repair of the 5{prime} part of the ADA gene is due to the rapid and efficient repair of the transcribed strand. Within 8 h after irradiation with UV at 10 J m-2, 70% of the pyrimidine dimers in this strand are removed. The nontranscribed strand is repaired at a much slower rate, with 30% dimersmore » removed after 8 h. Repair of the transcribed strand in XP-C cells occurs at a rate indistinguishable from that in normal cells, but the nontranscribed strand is not repaired significantly in these cells. Similar results were obtained for the DHFR gene. In the 3{prime} part of the ADA gene, however, both normal and XP-C cells perform fast and efficient repair of either strand, which is likely to be caused by the presence of transcription units on both strands. The factor defective in XP-C cells is apparently involved in the processing of DNA damage in inactive parts of the genome, including nontranscribed strands of active genes. These findings have important implications for the understanding of the mechanism of UV-induced excision repair and mutagenesis in mammalian cells.« less

Bioengineering approaches to study multidrug resistance in tumor cells

PubMed Central

Fallica, Brian; Makin, Guy

2015-01-01

The ability of cancer cells to become resistant to chemotherapeutic agents is a major challenge for the treatment of malignant tumors. Several strategies have emerged to attempt to inhibit chemoresistance, but the fact remains that resistance is a problem for every effective anticancer drug. The first part of this review will focus on the mechanisms of chemoresistance. It is important to understand the environmental cues, transport limitations and the cellular signaling pathways associated with chemoresistance before we can hope to effectively combat it. The second part of this review focuses on the work that needs to be done moving forward. Specifically, this section focuses on the necessity of translational research and interdisciplinary directives. It is critical that the expertise of oncologists, biologists, and engineers be brought together to attempt to tackle the problem. This discussion is from an engineering perspective, as the dialogue between engineers and other cancer researchers is the most challenging due to non-overlapping background knowledge. Chemoresistance is a complex and devastating process, meaning that we urgently need sophisticated methods to study the process of how cells become resistant. PMID:21387035

Electro-Optical Inspection For Tolerance Control As An Integral Part Of A Flexible Machining Cell

NASA Astrophysics Data System (ADS)

Renaud, Blaise

1986-11-01

Institut CERAC has been involved in optical metrology and 3-dimensional surface control for the last couple of years. Among the industrial applications considered is the on-line shape evaluation of machined parts within the manufacturing cell. The specific objective is to measure the machining errors and to compare them with the tolerances set by designers. An electro-optical sensing technique has been developed which relies on a projection Moire contouring optical method. A prototype inspection system has been designed, making use of video detection and computer image processing. Moire interferograms are interpreted, and the metrological information automatically retrieved. A structured database can be generated for subsequent data analysis and for real-time closed-loop corrective actions. A real-time kernel embedded into a synchronisation network (Petri-net) for the control of concurrent processes in the Electra-Optical Inspection (E0I) station was realised and implemented in a MODULA-2 program DIN01. The prototype system for on-line automatic tolerance control taking place within a flexible machining cell is described in this paper, together with the fast-prototype synchronisation program.

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

You, Jae-Hwan; Reed, Mark L.; Hiscox, Julian A.

The severe acute respiratory syndrome-coronavirus nucleocapsid (N) protein is involved in virus replication and modulation of cell processes. In this latter respect control may in part be achieved through the sub-cellular localisation of the protein. N protein predominately localises in the cytoplasm (the site of virus replication and assembly) but also in the nucleus/nucleolus. Using a combination of live-cell and confocal microscopy coupled to mutagenesis we identified a cryptic nucleolar localisation signal in the central part of the N protein. In addition, based on structural comparison to the avian coronavirus N protein, a nuclear export signal was identified in themore » C-terminal region of the protein.« less

Effects of Intercellular Junction Protein Expression on Intracellular Ice Formation in Mouse Insulinoma Cells

PubMed Central

Higgins, Adam Z.; Karlsson, Jens O.M.

2013-01-01

The development of cryopreservation procedures for tissues has proven to be difficult in part because cells within tissue are more susceptible to intracellular ice formation (IIF) than are isolated cells. In particular, previous studies suggest that cell-cell interactions increase the likelihood of IIF by enabling propagation of ice between neighboring cells, a process thought to be mediated by gap junction channels. In this study, we investigated the effects of cell-cell interactions on IIF using three genetically modified strains of the mouse insulinoma cell line MIN6, each of which expressed key intercellular junction proteins (connexin-36, E-cadherin, and occludin) at different levels. High-speed video cryomicroscopy was used to visualize the freezing process in pairs of adherent cells, revealing that the initial IIF event in a given cell pair was correlated with a hitherto unrecognized precursor phenomenon: penetration of extracellular ice into paracellular spaces at the cell-cell interface. Such paracellular ice penetration occurred in the majority of cell pairs observed, and typically preceded and colocalized with the IIF initiation events. Paracellular ice penetration was generally not observed at temperatures >−5.65°C, which is consistent with a penetration mechanism via defects in tight-junction barriers at the cell-cell interface. Although the maximum temperature of paracellular penetration was similar for all four cell strains, genetically modified cells exhibited a significantly higher frequency of ice penetration and a higher mean IIF temperature than did wild-type cells. A four-state Markov chain model was used to quantify the rate constants of the paracellular ice penetration process, the penetration-associated IIF initiation process, and the intercellular ice propagation process. In the initial stages of freezing (>−15°C), junction protein expression appeared to only have a modest effect on the kinetics of propagative IIF, and even cell strains lacking the gap junction protein connexin-36 exhibited nonnegligible ice propagation rates. PMID:24209845

Neuron analysis of visual perception

NASA Technical Reports Server (NTRS)

Chow, K. L.

1980-01-01

The receptive fields of single cells in the visual system of cat and squirrel monkey were studied investigating the vestibular input affecting the cells, and the cell's responses during visual discrimination learning process. The receptive field characteristics of the rabbit visual system, its normal development, its abnormal development following visual deprivation, and on the structural and functional re-organization of the visual system following neo-natal and prenatal surgery were also studied. The results of each individual part of each investigation are detailed.

Fate of nuclear material during subsequent steps of the kinetin-induced PCD in apical parts of Vicia faba ssp. minor seedling roots.

PubMed

Kaźmierczak, Andrzej; Soboska, Kamila

2018-07-01

In animals during apoptosis, the best examined type of programmed cell death (PCD), three main phases are distinguished: (i) specification (signaling), (ii) killing and (iii) execution one. It has bean postulated that plant PCD also involves three subsequent phases: (i) transmission of death signals to cells (signaling), (ii) initiation of killing processes and (iii) destruction of cells. One of the most important hallmarks of animal and plant PCD are those regarding nucleus, not thoroughly studied in plants so far. To study kinetin-induced PCD (Kin-PCD) in the context of nuclear material faith, 2-cm apical parts of Vicia faba ssp. minor seedling roots were used. Applied assays involving spectrophotometry, transmission electron microscopy, fluorescence and white light microscopy allowed to examine metabolic and cytomorphologic hallmarks such as changes in DNA content, ssDNA formation and activity of acidic and basic nucleases (DNases and RNases) as well as malformations and fragmentation of nucleoli and nuclei. The obtained results concerning the PCD hallmarks and influence of ZnSO 4 on Kin-PCD allowed us to confirmed presence of specification/signaling, killing and execution/degradation phases of the process and broaden the knowledge about processes affecting nuclei during PCD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Brain-peripheral cell crosstalk in white matter damage and repair.

PubMed

Hayakawa, Kazuhide; Lo, Eng H

2016-05-01

White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP.

PubMed

Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei; Zeng, Qiutang

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE-/- mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells.

Effects of surface nanostructuring and impurity doping on ultrafast carrier dynamics of silicon photovoltaic cells: a pump-probe study

NASA Astrophysics Data System (ADS)

Chen, Tianyu; Nam, Yoon-Ho; Wang, Xinke; Han, Peng; Sun, Wenfeng; Feng, Shengfei; Ye, Jiasheng; Song, Jae-Won; Lee, Jung-Ho; Zhang, Chao; Zhang, Yan

2018-01-01

We present femtosecond optical pump-terahertz probe studies on the ultrafast dynamical processes of photo-generated charge carriers in silicon photovoltaic cells with various nanostructured surfaces and doping densities. The pump-probe measurements provide direct insight on the lifetime of photo-generated carriers, frequency-dependent complex dielectric response along with photoconductivity of silicon photovoltaic cells excited by optical pump pulses. A lifetime of photo-generated carriers of tens of nanosecond is identified from the time-dependent pump-induced attenuation of the terahertz transmission. In addition, we find a large value of the imaginary part of the dielectric function and of the real part of the photoconductivity in silicon photovoltaic cells with micron length nanowires. We attribute these findings to the result of defect-enhanced electron-photon interactions. Moreover, doping densities of phosphorous impurities in silicon photovoltaic cells are also quantified using the Drude-Smith model with our measured frequency-dependent complex photoconductivities.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

PubMed Central

Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

Spermatogenesis, a study of germ cell development, is a long, orderly, and well-defined process occurring in seminiferous tubules of the testis. It is a temporal event whereby undifferentiated spermatogonial germ cells evolve into maturing spermatozoa over a period of several weeks. Spermatogenesis is characterized by three specific functional phases: proliferation, meiosis, and differentiation, and it involves spermatogonia, spermatocytes, and spermatids. Germ cells at steps of development form various cellular associations or stages, with 6, 12, and 14 specific stages being identified in human, mouse, and rat, respectively. The stages evolve over time in a given area of the seminiferous tubule forming a cycle of the seminiferous epithelium that has a well-defined duration for a given species. In this part, we discuss the proliferation and meiotic phase whereby spermatogonia undergo several mitotic divisions to form spermatocytes that undergo two meiotic divisions to form haploid spermatids. In the rat, spermatogonia can be subdivided into several classes: stem cells (A(s)), proliferating cells (A(pr), A(al)), and differentiating cells (A(1)-A(4), In, B). They are dependent on a specific microenvironment (niche) contributed by Sertoli, myoid, and Leydig cells for proper development. Spermatogonia possess several surface markers whereby they can be identified from each other. During meiosis, spermatocytes undergo chromosomal pairing, synapsis, and genetic exchange as well as transforming into haploid cells following meiosis. The meiotic cells form specific structural entities such as the synaptonemal complex and sex body. Many genes involved in spermatogonial renewal and the meiotic process have been identified and shown to be essential for this event. Copyright 2009 Wiley-Liss, Inc.

Crystalline silicon solar cells with high resistivity emitter

NASA Astrophysics Data System (ADS)

Panek, P.; Drabczyk, K.; Zięba, P.

2009-06-01

The paper presents a part of research targeted at the modification of crystalline silicon solar cell production using screen-printing technology. The proposed process is based on diffusion from POCl3 resulting in emitter with a sheet resistance on the level of 70 Ω/□ and then, shaped by high temperature passivation treatment. The study was focused on a shallow emitter of high resistivity and on its influence on output electrical parameters of a solar cell. Secondary ion mass spectrometry (SIMS) has been employed for appropriate distinguishing the total donor doped profile. The solar cell parameters were characterized by current-voltage characteristics and spectral response (SR) methods. Some aspects playing a role in suitable manufacturing process were discussed. The situation in a photovoltaic industry with emphasis on silicon supply and current prices of solar cells, modules and photovoltaic (PV) systems are described. The economic and quantitative estimation of the PV world market is shortly discussed.

Role of innate and adaptive immunity in obesity-associated metabolic disease

PubMed Central

McLaughlin, Tracey; Ackerman, Shelley E.; Shen, Lei

2017-01-01

Chronic inflammation in adipose tissue, possibly related to adipose cell hypertrophy, hypoxia, and/or intestinal leakage of bacteria and their metabolic products, likely plays a critical role in the development of obesity-associated insulin resistance (IR). Cells of both the innate and adaptive immune system residing in adipose tissues, as well as in the intestine, participate in this process. Thus, M1 macrophages, IFN-γ–secreting Th1 cells, CD8+ T cells, and B cells promote IR, in part through secretion of proinflammatory cytokines. Conversely, eosinophils, Th2 T cells, type 2 innate lymphoid cells, and possibly Foxp3+ Tregs protect against IR through local control of inflammation. PMID:28045397

Nicholas J. Grundl | NREL

Science.gov Websites

-3228 Research Interests Application of numerical methods to process problems Fuel and chemical biochemistry and numerical methods), University of Wisconsin at Madison, 2009-2014 Professional Experience Stem Cells Under Defined Conditions," Tissue Engineering Part C Methods (2013)

DNA repair and aging: the impact of the p53 family.

PubMed

Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

2015-12-01

Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR.

DNA repair and aging: the impact of the p53 family

PubMed Central

Nicolai, Sara; Rossi, Antonello; Di Daniele, Nicola; Melino, Gerry; Annicchiarico-Petruzzelli, Margherita; Raschellà, Giuseppe

2015-01-01

Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR. PMID:26668111

Epithelial-mesenchymal transition in colonies of rhesus monkey embryonic stem cells: a model for processes involved in gastrulation.

PubMed

Behr, Rüdiger; Heneweer, Carola; Viebahn, Christoph; Denker, Hans-Werner; Thie, Michael

2005-01-01

Rhesus monkey embryonic stem (rhES) cells were grown on mouse embryonic fibroblast (MEF) feeder layers for up to 10 days to form multilayered colonies. Within this period, stem cell colonies differentiated transiently into complex structures with a disc-like morphology. These complex colonies were characterized by morphology, immunohistochemistry, and marker mRNA expression to identify processes of epithelialization as well as epithelial-mesenchymal transition (EMT) and pattern formation. Typically, differentiated colonies were comprised of an upper and a lower ES cell layer, the former growing on top of the layer of MEF cells whereas the lower ES cell layer spread out underneath the MEF cells. Interestingly, in the central part of the colonies, a roundish pit developed. Here the feeder layer disappeared, and upper layer cells seemed to ingress and migrate through the pit downward to form the lower layer while undergoing a transition from the epithelial to the mesenchymal phenotype, which was indicated by the loss of the marker proteins E-cadherin and ZO-1 in the lower layer. In support of this, we found a concomitant 10-fold upregulation of the gene Snail2, which is a key regulator of the EMT process. Conversion of epiblast to mesoderm was also indicated by the regulated expression of the mesoderm marker Brachyury. An EMT is a characteristic process of vertebrate gastrulation. Thus, these rhES cell colonies may be an interesting model for studies on some basic processes involved in early primate embryogenesis and may open new ways to study the regulation of EMT in vitro.

Recent developments of downstream processing for microbial lipids and conversion to biodiesel.

PubMed

Yellapu, Sravan Kumar; Bharti; Kaur, Rajwinder; Kumar, Lalit R; Tiwari, Bhagyashree; Zhang, Xiaolei; Tyagi, Rajeshwar D

2018-05-01

With increasing global population and depleting resources, there is an apparent demand for radical unprecedented innovation to satisfy the basal needs of lives. Hence, non-conventional renewable energy resources like biodiesel have been worked out in past few decades. Biofuel (e.g. Biodiesel) serves to be the most sustainable answer to solve "food vs. fuel crisis". In biorefinery process, lipid extraction from oleaginous microbial lipids is an integral part as it facilitates the release of fatty acids. Direct lipid extraction from wet cell-biomass is favorable in comparison to dry-cell biomass because it eliminates the application of expensive dehydration. However, this process is not commercialized yet, instead, it requires intensive research and development in order to establish robust approaches for lipid extraction that can be practically applied on an industrial scale. This review aims for the critical presentation on cell disruption, lipid recovery and purification to support extraction from wet cell-biomass for an efficient transesterification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Heterogeneity in the development of the vertebra.

PubMed

Monsoro-Burq, A H; Bontoux, M; Teillet, M A; Le Douarin, N M

1994-10-25

Vertebrae are derived from the sclerotomal moities of the somites. Sclerotomal cells migrate ventrally to surround the notochord, where they form the vertebral body, and dorsolaterally to form the neural arch, which is dorsally closed by the spinous process. Precursor cells of the spinous process as well as superficial ectoderm and roof plate express homeobox genes of the Msh family from embryonic day 2 (E2) to E6. The notochord has been shown to be responsible for the dorsoventral polarization of the somites and for the induction of sclerotomal cells into cartilage. Indeed, supernumerary notochord grafted laterally to the neural tube induces the conversion of the entire somite into cartilage. We report here that a mediodorsal graft of notochord prevents the sclerotomal cells migrating dorsally to the roof plate from differentiating into cartilage. Under these experimental conditions, expression of Msx genes is abolished. We thus demonstrate that cartilaginous, differentiation is differentially controlled in the dorsal part of the vertebra (spinous process) and in the neural arch and vertebral body.

A hybrid magnetic/complementary metal oxide semiconductor three-context memory bit cell for non-volatile circuit design

NASA Astrophysics Data System (ADS)

Jovanović, B.; Brum, R. M.; Torres, L.

2014-04-01

After decades of continued scaling to the beat of Moore's law, it now appears that conventional silicon based devices are approaching their physical limits. In today's deep-submicron nodes, a number of short-channel and quantum effects are emerging that affect the manufacturing process, as well as, the functionality of the microelectronic systems-on-chip. Spintronics devices that exploit both the intrinsic spin of the electron and its associated magnetic moment, in addition to its fundamental electronic charge, are promising solutions to circumvent these scaling threats. Being compatible with the CMOS technology, such devices offer a promising synergy of radiation immunity, infinite endurance, non-volatility, increased density, etc. In this paper, we present a hybrid (magnetic/CMOS) cell that is able to store and process data both electrically and magnetically. The cell is based on perpendicular spin-transfer torque magnetic tunnel junctions (STT-MTJs) and is suitable for use in magnetic random access memories and reprogrammable computing (non-volatile registers, processor cache memories, magnetic field-programmable gate arrays, etc). To demonstrate the potential our hybrid cell, we physically implemented a small hybrid memory block using 45 nm × 45 nm round MTJs for the magnetic part and 28 nm fully depleted silicon on insulator (FD-SOI) technology for the CMOS part. We also report the cells measured performances in terms of area, robustness, read/write speed and energy consumption.

Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells

PubMed Central

Chmielewski, Markus; Hombach, Andreas A.; Abken, Hinrich

2013-01-01

Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient’s T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a “tumor-associated antigen” and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer. PMID:24273543

Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells.

PubMed

Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

2013-01-01

Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a "tumor-associated antigen" and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer.

KSC-2011-8202

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare to re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

KSC-2011-8201

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare to re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

KSC-2011-8199

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare to re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

KSC-2011-8200

NASA Image and Video Library

2011-12-09

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare to re-install the three fuel cells in space shuttle Discovery’s mid-body. The fuel cells were removed and drained of all fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Dimitri Gerondidakis

Modulation of eukaryotic cell apoptosis by members of the bacterial order Actinomycetales.

PubMed

Barry, Daniel P; Beaman, Blaine L

2006-10-01

Apoptosis, or programmed cell death, is normally responsible for the orderly elimination of aged or damaged cells, and is a necessary part of the homeostasis and development of multicellular organisms. Some pathogenic bacteria can disrupt this process by triggering excess apoptosis or by preventing it when appropriate. Either event can lead to disease. There has been extensive research into the modulation of host cell death by microorganisms, and several reviews have been published on the phenomenon. Rather than covering the entire field, this review focuses on the dysregulation of host cell apoptosis by members of the order Actinomycetales, containing the genera Corynebacterium, Mycobacterium, Rhodococcus, and Nocardia.

Long-term evaluation of solid oxide fuel cell candidate materials in a 3-cell generic short stack fixture, Part II: sealing glass stability, microstructure and interfacial reactions.

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

Chou, Y. S.; Stevenson, Jeffry W.; Choi, Jung-Pyung

2014-03-15

A generic solid oxide fuel cell stack test fixture was developed to evaluate candidate materials and processing methods under realistic conditions. Part I of the work addressed the stack fixture, seal system and cell performance of a 3-cell short stack tested at 800oC for 6000h. Commercial NiO-YSZ anode-supported thin YSZ electrolyte cells with LSM cathodes were used for assessment and were tested in constant current mode with dilute (~50% H2) fuel versus air. Part II of the work examined the sealing glass stability, microstructure development, interfacial reactions, and volatility issues. Part III of the work investigated the stability of Ce-(Mn,Co)more » spinel coating, AISI441 metallic interconnect, alumina coating, and cell degradation. After 6000h of testing, the refractory sealing glass YSO77 (Ba-Sr-Y-B-Si) showed desirable chemical compatibility with YSZ electrolyte in that no discernable interfacial reaction was identified, consistent with thermodynamic calculations. In addition, no glass penetration into the thin electrolyte was observed. At the aluminized AISI441 interface, the protective alumina coating appeared to be corroded by the sealing glass. Air side interactions appeared to be more severe than fuel side interactions. Metal species such as Cr, Mn, and Fe were detected in the glass, but were limited to the vicinity of the interface. No alkaline earth chromates were found at the air side. Volatility was also studied in a similar glass and weight loss in a wet reducing environment was determined. Using the steady-state volatility data, the life time (40,000h) weight loss of refractory sealing glass YSO77 was estimated to be less than 0.1 wt%.« less

Recent Advances in the Inverted Planar Structure of Perovskite Solar Cells.

PubMed

Meng, Lei; You, Jingbi; Guo, Tzung-Fang; Yang, Yang

2016-01-19

Inorganic-organic hybrid perovskite solar cells research could be traced back to 2009, and initially showed 3.8% efficiency. After 6 years of efforts, the efficiency has been pushed to 20.1%. The pace of development was much faster than that of any type of solar cell technology. In addition to high efficiency, the device fabrication is a low-cost solution process. Due to these advantages, a large number of scientists have been immersed into this promising area. In the past 6 years, much of the research on perovskite solar cells has been focused on planar and mesoporous device structures employing an n-type TiO2 layer as the bottom electron transport layer. These architectures have achieved champion device efficiencies. However, they still possess unwanted features. Mesoporous structures require a high temperature (>450 °C) sintering process for the TiO2 scaffold, which will increase the cost and also not be compatible with flexible substrates. While the planar structures based on TiO2 (regular structure) usually suffer from a large degree of J-V hysteresis. Recently, another emerging structure, referred to as an "inverted" planar device structure (i.e., p-i-n), uses p-type and n-type materials as bottom and top charge transport layers, respectively. This structure derived from organic solar cells, and the charge transport layers used in organic photovoltaics were successfully transferred into perovskite solar cells. The p-i-n structure of perovskite solar cells has shown efficiencies as high as 18%, lower temperature processing, flexibility, and, furthermore, negligible J-V hysteresis effects. In this Account, we will provide a comprehensive comparison of the mesoporous and planar structures, and also the regular and inverted of planar structures. Later, we will focus the discussion on the development of the inverted planar structure of perovskite solar cells, including film growth, band alignment, stability, and hysteresis. In the film growth part, several methods for obtaining high quality perovskite films are reviewed. In the interface engineering parts, the effect of hole transport layer on subsequent perovskite film growth and their interface band alignment, and also the effect of electron transport layers on charge transport and interface contact will be discussed. As concerns stability, the role of charge transport layers especially the top electron transport layer in the devices stability will be concluded. In the hysteresis part, possible reasons for hysteresis free in inverted planar structure are provided. At the end of this Account, future development and possible solutions to the remaining challenges facing the commercialization of perovskite solar cells are discussed.

Mycoplasma pneumoniae, an Underutilized Model for Bacterial Cell Biology

PubMed Central

2014-01-01

In recent decades, bacterial cell biology has seen great advances, and numerous model systems have been developed to study a wide variety of cellular processes, including cell division, motility, assembly of macromolecular structures, and biogenesis of cell polarity. Considerable attention has been given to these model organisms, which include Escherichia coli, Bacillus subtilis, Caulobacter crescentus, and Myxococcus xanthus. Studies of these processes in the pathogenic bacterium Mycoplasma pneumoniae and its close relatives have also been carried out on a smaller scale, but this work is often overlooked, in part due to this organism's reputation as minimalistic and simple. In this minireview, I discuss recent work on the role of the M. pneumoniae attachment organelle (AO), a structure required for adherence to host cells, in these processes. The AO is constructed from proteins that generally lack homology to those found in other organisms, and this construction occurs in coordination with cell cycle events. The proteins of the M. pneumoniae AO share compositional features with proteins with related roles in model organisms. Once constructed, the AO becomes activated for its role in a form of gliding motility whose underlying mechanism appears to be distinct from that of other gliding bacteria, including Mycoplasma mobile. Together with the FtsZ cytoskeletal protein, motility participates in the cell division process. My intention is to bring this deceptively complex organism into alignment with the better-known model systems. PMID:25157081

Automated platform for designing multiple robot work cells

NASA Astrophysics Data System (ADS)

Osman, N. S.; Rahman, M. A. A.; Rahman, A. A. Abdul; Kamsani, S. H.; Bali Mohamad, B. M.; Mohamad, E.; Zaini, Z. A.; Rahman, M. F. Ab; Mohamad Hatta, M. N. H.

2017-06-01

Designing the multiple robot work cells is very knowledge-intensive, intricate, and time-consuming process. This paper elaborates the development process of a computer-aided design program for generating the multiple robot work cells which offer a user-friendly interface. The primary purpose of this work is to provide a fast and easy platform for less cost and human involvement with minimum trial and errors adjustments. The automated platform is constructed based on the variant-shaped configuration concept with its mathematical model. A robot work cell layout, system components, and construction procedure of the automated platform are discussed in this paper where integration of these items will be able to automatically provide the optimum robot work cell design according to the information set by the user. This system is implemented on top of CATIA V5 software and utilises its Part Design, Assembly Design, and Macro tool. The current outcomes of this work provide a basis for future investigation in developing a flexible configuration system for the multiple robot work cells.

Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer.

PubMed

Nurwidya, Fariz; Zaini, Jamal; Putra, Andika Chandra; Andarini, Sita; Hudoyo, Achmad; Syahruddin, Elisna; Yunus, Faisal

2016-09-01

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.

The actin cytoskeleton in whole mount preparations and sections.

PubMed

Resch, Guenter P; Urban, Edit; Jacob, Sonja

2010-01-01

In non-muscle cells, the actin cytoskeleton plays a key role by providing a scaffold contributing to the definition of cell shape, force for driving cell motility, cytokinesis, endocytosis, and propulsion of pathogens, as well as tracks for intracellular transport. A thorough understanding of these processes requires insight into the spatial and temporal organisation of actin filaments into diverse higher-order structures, such as networks, parallel bundles, and contractile arrays. Transmission and scanning electron microscopy can be used to visualise the actin cytoskeleton, but due to the delicate nature of actin filaments, they are easily affected by standard preparation protocols, yielding variable degrees of ultrastructural preservation. In this chapter, we describe different conventional and cryo-approaches to visualise the actin cytoskeleton using transmission electron microscopy and discuss their specific advantages and drawbacks. In the first part, we present three different whole mount techniques, which allow visualisation of actin in the peripheral, thinly spread parts of cells grown in monolayers. In the second part, we describe specific issues concerning the visualisation of actin in thin sections. Techniques for three-dimensional visualisation of actin, protein localisation, and correlative light and electron microscopy are also included. Copyright © 2010 Elsevier Inc. All rights reserved.

Dynamic analysis of the combinatorial regulation involving transcription factors and microRNAs in cell fate decisions.

PubMed

Yan, Fang; Liu, Haihong; Liu, Zengrong

2014-01-01

P53 and E2F1 are critical transcription factors involved in the choices between different cell fates including cell differentiation, cell cycle arrest or apoptosis. Recent experiments have shown that two families of microRNAs (miRNAs), p53-responsive miR34 (miRNA-34 a, b and c) and E2F1-inducible miR449 (miRNA-449 a, b and c) are potent inducers of these different fates and might have an important role in sensitizing cancer cells to drug treatment and tumor suppression. Identifying the mechanisms responsible for the combinatorial regulatory roles of these two transcription factors and two miRNAs is an important and challenging problem. Here, based in part on the model proposed in Tongli Zhang et al. (2007), we developed a mathematical model of the decision process and explored the combinatorial regulation between these two transcription factors and two miRNAs in response to DNA damage. By analyzing nonlinear dynamic behaviors of the model, we found that p53 exhibits pulsatile behavior. Moreover, a comparison is given to reveal the subtle differences of the cell fate decision process between regulation and deregulation of miR34 on E2F1. It predicts that miR34 plays a critical role in promoting cell cycle arrest. In addition, a computer simulation result also predicts that the miR449 is necessary for apoptosis in response to sustained DNA damage. In agreement with experimental observations, our model can account for the intricate regulatory relationship between these two transcription factors and two miRNAs in the cell fate decision process after DNA damage. These theoretical results indicate that miR34 and miR449 are effective tumor suppressors and play critical roles in cell fate decisions. The work provides a dynamic mechanism that shows how cell fate decisions are coordinated by two transcription factors and two miRNAs. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology and Clinical Implications. Guest Editor: Yudong Cai. Crown Copyright © 2013. All rights reserved.

Existence and stability of periodic solutions of an impulsive differential equation and application to CD8 T-cell differentiation.

PubMed

Girel, Simon; Crauste, Fabien

2018-06-01

Unequal partitioning of the molecular content at cell division has been shown to be a source of heterogeneity in a cell population. We propose to model this phenomenon with the help of a scalar, nonlinear impulsive differential equation (IDE). To study the effect of molecular partitioning at cell division on the effector/memory cell-fate decision in a CD8 T-cell lineage, we study an IDE describing the concentration of the protein Tbet in a CD8 T-cell, where impulses are associated to cell division. We discuss how the degree of asymmetry of molecular partitioning can affect the process of cell differentiation and the phenotypical heterogeneity of a cell population. We show that a moderate degree of asymmetry is necessary and sufficient to observe irreversible differentiation. We consider, in a second part, a general autonomous IDE with fixed times of impulse and a specific form of impulse function. We establish properties of the solutions of that equation, most of them obtained under the hypothesis that impulses occur periodically. In particular, we show how to investigate the existence of periodic solutions and their stability by studying the flow of an autonomous differential equation. Then we apply those properties to prove the results presented in the first part.

Automated classification of bone marrow cells in microscopic images for diagnosis of leukemia: a comparison of two classification schemes with respect to the segmentation quality

NASA Astrophysics Data System (ADS)

Krappe, Sebastian; Benz, Michaela; Wittenberg, Thomas; Haferlach, Torsten; Münzenmayer, Christian

2015-03-01

The morphological analysis of bone marrow smears is fundamental for the diagnosis of leukemia. Currently, the counting and classification of the different types of bone marrow cells is done manually with the use of bright field microscope. This is a time consuming, partly subjective and tedious process. Furthermore, repeated examinations of a slide yield intra- and inter-observer variances. For this reason an automation of morphological bone marrow analysis is pursued. This analysis comprises several steps: image acquisition and smear detection, cell localization and segmentation, feature extraction and cell classification. The automated classification of bone marrow cells is depending on the automated cell segmentation and the choice of adequate features extracted from different parts of the cell. In this work we focus on the evaluation of support vector machines (SVMs) and random forests (RFs) for the differentiation of bone marrow cells in 16 different classes, including immature and abnormal cell classes. Data sets of different segmentation quality are used to test the two approaches. Automated solutions for the morphological analysis for bone marrow smears could use such a classifier to pre-classify bone marrow cells and thereby shortening the examination duration.

Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

PubMed

Guzzo, M F; Carvalho, L R S; Bronstein, M D

2014-04-01

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

A synthetic mammalian electro-genetic transcription circuit.

PubMed

Weber, Wilfried; Luzi, Stefan; Karlsson, Maria; Sanchez-Bustamante, Carlota Diaz; Frey, Urs; Hierlemann, Andreas; Fussenegger, Martin

2009-03-01

Electric signal processing has evolved to manage rapid information transfer in neuronal networks and muscular contraction in multicellular organisms and controls the most sophisticated man-built devices. Using a synthetic biology approach to assemble electronic parts with genetic control units engineered into mammalian cells, we designed an electric power-adjustable transcription control circuit able to integrate the intensity of a direct current over time, to translate the amplitude or frequency of an alternating current into an adjustable genetic readout or to modulate the beating frequency of primary heart cells. Successful miniaturization of the electro-genetic devices may pave the way for the design of novel hybrid electro-genetic implants assembled from electronic and genetic parts.

A synthetic mammalian electro-genetic transcription circuit

PubMed Central

Weber, Wilfried; Luzi, Stefan; Karlsson, Maria; Sanchez-Bustamante, Carlota Diaz; Frey, Urs; Hierlemann, Andreas; Fussenegger, Martin

2009-01-01

Electric signal processing has evolved to manage rapid information transfer in neuronal networks and muscular contraction in multicellular organisms and controls the most sophisticated man-built devices. Using a synthetic biology approach to assemble electronic parts with genetic control units engineered into mammalian cells, we designed an electric power-adjustable transcription control circuit able to integrate the intensity of a direct current over time, to translate the amplitude or frequency of an alternating current into an adjustable genetic readout or to modulate the beating frequency of primary heart cells. Successful miniaturization of the electro-genetic devices may pave the way for the design of novel hybrid electro-genetic implants assembled from electronic and genetic parts. PMID:19190091

Leptin-like immunoreactivity in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii.

PubMed

Poljaroen, Jaruwan; Tinikul, Yotsawan; Tinikul, Ruchanok; Anurucpreeda, Panat; Sobhon, Prasert

2017-06-01

Leptin, a highly conserved adipocyte-derived hormone, plays important roles in a variety of physiological processes, including the control of fat storage and metabolic status which are linked to food intake, energy homeostasis, and reproduction in all vertebrates. In the present study, we hypothesize that leptin is also present in various organs of the fresh water prawns, Macrobrachium rosenbergii. The existence and distribution of a leptin-like peptide in prawn tissues were verified by using Western blotting (WB) and immunohistochemical detection (ID) using primary antibody against human leptin. With WB, a leptin-like peptide, having a molecular weight of 15kDa, was detected in the brain, thoracic ganglia, abdominal ganglia, parts of the gastro-intestinal tract, hepatopancreas, adipocytes and gonads. By ID, leptin immunoreactivity (leptin-ir) was detected in the brain, thoracic ganglia and intersegmental commissural nerve fibers of abdominal ganglia. In the gastrointestinal tract, there was intense leptin-ir in the apical part of the epithelial cells of the cardiac and pyloric parts of the stomach. In the midgut and hindgut, the leptin-ir was detected in epithelial cells and basal cells located near the basal lamina of the epithelium. In addition, there was leptin-ir in the Restzellen cells in the hepatopancreas which produce digestive enzymes. In the ovary, the strong intensity of a leptin-ir was detected in the cytoplasm of middle to late stage oocytes, whereas no positive staining was detected in follicular cells. An intense leptin-ir was detected in spermatocytes and sustentacular cells in the seminiferous tubules in the testes of small and orange claw males. Taken together, the detection of the leptin-ir in several organs implicates the existence of a leptin-like peptide in various organs of the freshwater prawn; and like in vertebrates this peptide may be an important hormonal factor in controlling feeding and reproductive process. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

Zidan, Ragaiy

A process of using an electrochemical cell to generate aluminum hydride (AlH.sub.3) and other high capacity hydrides is provided. The electrolytic cell uses an electro-catalytic-additive within a polar non-salt containing solvent to solubilize an ionic hydride such as NaAlH.sub.4 or LiAlH.sub.4. The resulting electrochemical process results in the formation of AlH.sub.3 adduct. AlH.sub.3 is obtained from the adduct by heating under vacuum. The AlH.sub.3 can be recovered and used as a source of hydrogen for the automotive industry. The resulting spent aluminum can be regenerated into NaAlH.sub.4 or LiAlH.sub.4 as part of a closed loop process of AlH.sub.3 generation.

Control of DNA replication: a new facet of Hox proteins?

PubMed

Miotto, Benoit; Graba, Yacine

2010-09-01

Hox proteins are well-known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox-mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications of this new facet of Hox protein function.

A Look into the Cell: Honey Storage in Honey Bees, Apis mellifera.

PubMed

Eyer, Michael; Neumann, Peter; Dietemann, Vincent

2016-01-01

Honey bees, Apis species, obtain carbohydrates from nectar and honeydew. These resources are ripened into honey in wax cells that are capped for long-term storage. These stores are used to overcome dearth periods when foraging is not possible. Despite the economic and ecological importance of honey, little is known about the processes of its production by workers. Here, we monitored the usage of storage cells and the ripening process of honey in free-flying A. mellifera colonies. We provided the colonies with solutions of different sugar concentrations to reflect the natural influx of nectar with varying quality. Since the amount of carbohydrates in a solution affects its density, we used computer tomography to measure the sugar concentration of cell content over time. The data show the occurrence of two cohorts of cells with different provisioning and ripening dynamics. The relocation of the content of many cells before final storage was part of the ripening process, because sugar concentration of the content removed was lower than that of content deposited. The results confirm the mixing of solutions of different concentrations in cells and show that honey is an inhomogeneous matrix. The last stage of ripening occurred when cell capping had already started, indicating a race against water absorption. The storage and ripening processes as well as resource use were context dependent because their dynamics changed with sugar concentration of the food. Our results support hypotheses regarding honey production proposed in earlier studies and provide new insights into the mechanisms involved.

An automated approach for single-cell tracking in epifluorescence microscopy applied to E. coli growth analysis on microfluidics biochips

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Kirov, Boris; Jaramillo, Alfonso; Lefevre, Christophe

2012-03-01

With the accumulation of knowledge for the intimate molecular mechanisms governing the processes inside the living cells in the later years, the ability to characterize the performance of elementary genetic circuits and parts at the single-cell level is becoming of crucial importance. Biological science is arriving to the point where it can develop hypothesis for the action of each molecule participating in the biochemical reactions and need proper techniques to test those hypothesis. Microfluidics is emerging as the technology that combined with high-magnification microscopy will allow for the long-term single-cell level observation of bacterial physiology. In this study we design, build and characterize the gene dynamics of genetic circuits as one of the basic parts governing programmed cell behavior. We use E. coli as model organism and grow it in microfluidics chips, which we observe with epifluorescence microscopy. One of the most invaluable segments of this technology is the consequent image processing, since it allows for the automated analysis of vast amount of single-cell observation and the fast and easy derivation of conclusions based on that data. Specifically, we are interested in promoter activity as function of time. We expect it to be oscillatory and for that we use GFP (green fluorescent protein) as a reporter in our genetic circuits. In this paper, an automated framework for single-cell tracking in phase-contrast microscopy is developed, combining 2D segmentation of cell time frames and graph-based reconstruction of their spatiotemporal evolution with fast tracking of the associated fluorescence signal. The results obtained on the investigated biological database are presented and discussed.

Large-scale production of diesel-like biofuels - process design as an inherent part of microorganism development.

PubMed

Cuellar, Maria C; Heijnen, Joseph J; van der Wielen, Luuk A M

2013-06-01

Industrial biotechnology is playing an important role in the transition to a bio-based economy. Currently, however, industrial implementation is still modest, despite the advances made in microorganism development. Given that the fuels and commodity chemicals sectors are characterized by tight economic margins, we propose to address overall process design and efficiency at the start of bioprocess development. While current microorganism development is targeted at product formation and product yield, addressing process design at the start of bioprocess development means that microorganism selection can also be extended to other critical targets for process technology and process scale implementation, such as enhancing cell separation or increasing cell robustness at operating conditions that favor the overall process. In this paper we follow this approach for the microbial production of diesel-like biofuels. We review current microbial routes with both oleaginous and engineered microorganisms. For the routes leading to extracellular production, we identify the process conditions for large scale operation. The process conditions identified are finally translated to microorganism development targets. We show that microorganism development should be directed at anaerobic production, increasing robustness at extreme process conditions and tailoring cell surface properties. All the same time, novel process configurations integrating fermentation and product recovery, cell reuse and low-cost technologies for product separation are mandatory. This review provides a state-of-the-art summary of the latest challenges in large-scale production of diesel-like biofuels. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cavity Processing and Preparation of 650 MHz Elliptical Cell Cavities for PIP-II

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

Rowe, Allan; Chandrasekaran, Saravan Kumar; Grassellino, Anna

The PIP-II project at Fermilab requires fifteen 650 MHz SRF cryomodules as part of the 800 MeV LINAC that will provide a high intensity proton beam to the Fermilab neutrino program. A total of fifty-seven high-performance SRF cavities will populate the cryomodules and will operate in both pulsed and continuous wave modes. These cavities will be processed and prepared for performance testing utilizing adapted cavity processing infrastructure already in place at Fermilab and Argonne. The processing recipes implemented for these structures will incorporate state-of-the art processing and cleaning techniques developed for 1.3 GHz SRF cavities for the ILC, XFEL, andmore » LCLS-II projects. This paper describes the details of the processing recipes and associated chemistry, heat treatment, and cleanroom processes at the Fermilab and Argonne cavity processing facilities. This paper also presents single and multi-cell cavity test results with quality factors above 5·10¹⁰ and accelerating gradients above 30 MV/m.« less

Hemoglobins, programmed cell death and somatic embryogenesis.

PubMed

Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

2013-10-01

Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Katkova, Olena

Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bones metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in perivascular cells population. It is one of the mechanisms of the osteogenic process intensity decrease in bones due to lowering support loading on the bone skeleton. In particular this is confirmed by the fact that in the zones of adaptive remodeling we found fibroblasts and fibrosis zones - areas filled with non mineralized collagen fibrils on the bones surfaces. Hence it should be considered that lowering (removal) support loading slows down (or blocks) osteogenic differentiation of the perivascular cells part and stimulates differentiation of the fibroblast cells. Obtained data considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

PubMed

Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

2004-10-01

Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

Collecting Duct Intercalated Cell Function and Regulation

PubMed Central

Roy, Ankita; Al-bataineh, Mohammad M.

2015-01-01

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule. PMID:25632105

KSC-2011-8346

NASA Image and Video Library

2011-12-21

CAPE CANAVERAL, Fla. --Three fuel cells recently removed from space shuttle Atlantis stand on tables in Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida. The fuel cells produced electricity for shuttles in space by combining liquid oxygen and liquid hydrogen. They were removed as part of the ongoing work to prepare the shuttles for public display. The shuttle is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Jim Grossmann

KSC-2011-8347

NASA Image and Video Library

2011-12-21

CAPE CANAVERAL, Fla. -- Three fuel cells recently removed from space shuttle Atlantis stand on tables in Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida. The fuel cells produced electricity for shuttles in space by combining liquid oxygen and liquid hydrogen. They were removed as part of the ongoing work to prepare the shuttles for public display. The shuttle is being prepared for display at the Kennedy Space Center Visitor Complex. Photo credit: NASA/Jim Grossmann

The tumor microenvironment: An irreplaceable element of tumor budding and epithelial-mesenchymal transition-mediated cancer metastasis

PubMed Central

Li, Hui; Xu, Fangying; Li, Si; Zhong, Anjing; Meng, Xianwen; Lai, Maode

2016-01-01

ABSTRACT Tumor budding occurs at the invasive front of cancer; the tumor cells involved have metastatic and stemness features, indicating a poor prognosis. Tumor budding is partly responsible for cancer metastasis, and its initiation is based on the epithelial-mesenchymal transition (EMT) process. The EMT process involves the conversion of epithelial cells into migratory and invasive cells, and is a profound event in tumorigenesis. The EMT, associated with the formation of cancer stem cells (CSCs) and resistance to therapy, results from a combination of gene mutation, epigenetic regulation, and microenvironmental control. Tumor budding can be taken to represent the EMT in vivo. The EMT process is under the influence of the tumor microenvironment as well as tumor cells themselves. Here, we demonstrate that the tumor microenvironment dominates EMT development and impacts cancer metastasis, as well as promotes CSC formation and mediates drug resistance. In this review, we mainly discuss components of the microenvironment, such as the extracellular matrix (ECM), inflammatory cytokines, metabolic products, and hypoxia, that are involved in and impact on the acquisition of tumor-cell motility and dissemination, the EMT, metastatic tumor-cell formation, tumor budding and CSCs, and cancer metastasis, including subsequent chemo-resistance. From our point of view, the tumor microenvironment now constitutes a promising target for cancer therapy. PMID:26743180

Modifying an Insect Cell N-Glycan Processing Pathway Using CRISPR-Cas Technology.

PubMed

Mabashi-Asazuma, Hideaki; Kuo, Chu-Wei; Khoo, Kay-Hooi; Jarvis, Donald L

2015-10-16

Fused lobes (FDL) is an enzyme that simultaneously catalyzes a key trimming reaction and antagonizes elongation reactions in the insect N-glycan processing pathway. Accordingly, FDL function accounts, at least in part, for major differences in the N-glycosylation patterns of glycoproteins produced by insect and mammalian cells. In this study, we used the CRISPR-Cas9 system to edit the fdl gene in Drosophila melanogaster S2 cells. CRISPR-Cas9 editing produced a high frequency of site-specific nucleotide insertions and deletions, reduced the production of insect-type, paucimannosidic products (Man3GlcNAc2), and led to the production of partially elongated, mammalian-type complex N-glycans (GlcNAc2Man3GlcNAc2) in S2 cells. As CRISPR-Cas9 has not been widely used to analyze or modify protein glycosylation pathways or edit insect cell genes, these results underscore its broad utility as a tool for these purposes. Our results also confirm the key role of FDL at the major branch point distinguishing insect and mammalian N-glycan processing pathways. Finally, the new FDL-deficient S2 cell derivative produced in this study will enable future bottom-up glycoengineering efforts designed to isolate insect cell lines that can efficiently produce recombinant glycoproteins with chemically predefined oligosaccharide side-chain structures.

Potential radiological impact of tornadoes on the safety of Nuclear Fuel Services' West Valley Fuel Reprocessing Plant. 2. Reentrainment and discharge of radioactive materials

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

Davis, W Jr

1981-07-01

This report describes results of a parametric study of quantities of radioactive materials that might be discharged by a tornado-generated depressurization on contaminated process cells within the presently inoperative Nuclear Fuel Services' (NFS) fuel reprocessing facility near West Valley, New York. The study involved the following tasks: determining approximate quantities of radioactive materials in the cells and characterizing particle-size distribution; estimating the degree of mass reentrainment from particle-size distribution and from air speed data presented in Part 1; and estimating the quantities of radioactive material (source term) released from the cells to the atmosphere. The study has shown that improperlymore » sealed manipulator ports in the Process Mechanical Cell (PMC) present the most likely pathway for release of substantial quantities of radioactive material in the atmosphere under tornado accident conditions at the facility.« less

Postnatal Exocrine Pancreas Growth by Cellular Hypertrophy Correlates with a Shorter Lifespan in Mammals.

PubMed

Anzi, Shira; Stolovich-Rain, Miri; Klochendler, Agnes; Fridlich, Ori; Helman, Aharon; Paz-Sonnenfeld, Avital; Avni-Magen, Nili; Kaufman, Elizabeth; Ginzberg, Miriam B; Snider, Daniel; Ray, Saikat; Brecht, Michael; Holmes, Melissa M; Meir, Karen; Avivi, Aaron; Shams, Imad; Berkowitz, Asaf; Shapiro, A M James; Glaser, Benjamin; Ben-Sasson, Shmuel; Kafri, Ran; Dor, Yuval

2018-06-18

Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia. Pancreatic acinar cell volume varies 9-fold among 24 mammalian species analyzed, and shows a striking inverse correlation with organismal lifespan. We hypothesize that cellular hypertrophy is a strategy for rapid postnatal tissue growth, entailing life-long detrimental effects. Copyright © 2018 Elsevier Inc. All rights reserved.

A systems analysis of the erythropoietic responses to weightlessness. Volume 2: Description of the model of erythropoiesis regulation. Part A: Model for regulation of erythropoiesis. Part B: Detailed description of the model for regulation of erythropoiesis

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

A mathematical model of the erythropoiesis on total red blood cell mass is presented. The loss of red cell mass has been a consistent finding during space flight. Computer simulation of this phenomenon required a model that could account for oxygen transport, red cell production, and red cell destruction. The elements incorporated into the feedback regulation loop of the model are based on the accepted concept that erythrocyte production is governed by the balance between oxygen supply and demand in the body. The mechanisms and pathways of the control circuit include oxygenation of hemoglobin and oxygenation of tissues by blood transport and diffusional processes. Other features of the model include a variable oxygen-hemoglobin affinity, and time delays which represent time for erythropoietin (erythrocyte-stimulating hormone) distribution in plasma, and time for maturation of the erythrocytes in bone marrow.

Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

NASA Astrophysics Data System (ADS)

Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

2016-07-01

Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular cells reveal signs of destruction. Thus it was found that number of the alkaline phosphatase containing cells (i.e. osteogenic cells) declines in perivascular cells population. It is one of the mechanisms of the osteogenic process decrease of intensity in bones because of lessening support loading on the bone skeleton. In the adaptive remodeling zones of bone tissue (near the vascular canals) in experiments fibroblasts and fibrosis zones were found - areas filled with non-mineralized collagen fibrils on the bones surfaces. Hence it should be considered that decrease (removal) of support loading slows down osteogenic differentiation of the part of perivascular cells and stimulates differentiation of the fibroblast cells. Obtained data is considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

KSC-2011-8062

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as space shuttle Discovery’s fuel cells are drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

KSC-2011-8059

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, a technician prepares one of space shuttle Discovery’s three fuel cells to be drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

KSC-2011-8058

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare space shuttle Discovery’s three fuel cells to be drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

KSC-2011-8060

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as space shuttle Discovery’s fuel cells are drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

KSC-2011-8057

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians prepare space shuttle Discovery’s three fuel cells to be drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

KSC-2011-8061

NASA Image and Video Library

2011-11-28

CAPE CANAVERAL, Fla. -- Inside Orbiter Processing Facility-1 at NASA’s Kennedy Space Center in Florida, technicians monitor the progress as space shuttle Discovery’s fuel cells are drained of all fluids. After all of the coolant is removed, the fuel cells will be returned to their previous location within Discovery’s mid-body. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Discovery’s mid-body and have been purged with inert gases and vented down. The work is part of the Space Shuttle Program’s transition and retirement processing of shuttle Discovery. Discovery is being prepared for display at the Smithsonian’s National Air and Space Museum, Steven F. Udvar-Hazy Center in Chantilly, Va. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Frankie Martin

BAG3 is upregulated by c-Jun and stabilizes JunD.

PubMed

Li, Chao; Li, Si; Kong, De-Hui; Meng, Xin; Zong, Zhi-Hong; Liu, Bao-Qin; Guan, Yifu; Du, Zhen-Xian; Wang, Hua-Qin

2013-12-01

BAG3 plays a regulatory role in a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, epithelial-mesenchymal transition (EMT), autophagy activation, and virus infection. The AP-1 transcription factors are implicated in a variety of important biological processes including cell differentiation, proliferation, apoptosis and oncogenesis. Recently, it has been reported that AP-1 protein c-Jun inhibits autophagy and enhances apoptotic cell death mediated by starvation. However, the molecular mechanisms remain unclear. For the first time, the current study demonstrated that serum starvation downregulated BAG3 at the transcriptional level via c-Jun. In addition, the current study reported that BAG3 stabilized JunD mRNA, which was, at least in part, responsible for the promotion of serum starvation mediated-growth inhibition by BAG3. © 2013.

Exposure to Melan-A/MART-126-35 tumor epitope specific CD8+T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS)

PubMed Central

Ebstein, Frédéric; Keller, Martin; Paschen, Annette; Walden, Peter; Seeger, Michael; Bürger, Elke; Krüger, Elke; Schadendorf, Dirk; Kloetzel, Peter-M.; Seifert, Ulrike

2016-01-01

Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to altered expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation of p97/VCP expression, which is an IFN-γ-independent component of the UPS and part of the ER-dependent protein degradation pathway (ERAD), was found to be essentially involved in the observed immune escape. In support, our data demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant melanoma cells completely restored immune recognition by Melan-A/MART-126-35 CTL. In conclusion, our experiments show that impaired expression of IFN-γ-independent components of the UPS can exert rapid immune evasion of tumor cells and suggest that tumor antigens processed by distinct UPS degradation pathways should be simultaneously targeted in T cell therapies to restrict the likelihood of immune evasion due to impaired antigen processing. PMID:27143649

Alcohol reversibly disrupts TNF-α/TACE interactions in the cell membrane

PubMed Central

Song, Kejing; Zhao, Xue-Jun; Marrero, Luis; Oliver, Peter; Nelson, Steve; Kolls, Jay K

2005-01-01

Background Alcohol abuse has long been known to adversely affect innate and adaptive immune responses and pre-dispose to infections. One cellular mechanism responsible for this effect is alcohol-induced suppression of TNF-α (TNF) by mononuclear phagocytes. We have previously shown that alcohol in part inhibits TNF-α processing by TNF converting enzyme (TACE) in human monocytes. We hypothesized that the chain length of the alcohol is critical for post-transcriptional suppression of TNF secretion. Methods Due to the complex transcriptional and post-transcriptional regulation of TNF in macrophages, to specifically study TNF processing at the cell membrane we performed transient transfections of A549 cells with the TNF cDNA driven by the heterologous CMV promoter. TNF/TACE interactions at the cell surface were assessed using fluorescent resonance energy transfer (FRET) microscopy. Results The single carbon alcohol, methanol suppressed neither TNF secretion nor FRET efficiency between TNF and TACE. However, 2, 3, and 4 carbon alcohols were potent suppressors of TNF processing and FRET efficiency. The effect of ethanol, a 2-carbon alcohol was reversible. Conclusion These data show that inhibition of TNF-α processing by acute ethanol is a direct affect of ethanol on the cell membrane and is reversible upon cessation or metabolism. PMID:16246259

Biomarker analysis of liver cells exposed to surfactant-wrapped and oxidized multi-walled carbon nanotubes (MWCNTs)

EPA Science Inventory

Carbon nanotubes (CNTs) have great potential in industrial, consumer, and mechanical applications, based partly on their unique structural, optical and electronic properties. CNTs are commonly oxidized or treated with surfactants to facilitate aqueous solution processing, and the...

Development and plasticity of meningeal lymphatic vessels.

PubMed

Antila, Salli; Karaman, Sinem; Nurmi, Harri; Airavaara, Mikko; Voutilainen, Merja H; Mathivet, Thomas; Chilov, Dmitri; Li, Zhilin; Koppinen, Tapani; Park, Jun-Hee; Fang, Shentong; Aspelund, Aleksanteri; Saarma, Mart; Eichmann, Anne; Thomas, Jean-Léon; Alitalo, Kari

2017-12-04

The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. © 2017 Antila et al.

Development and plasticity of meningeal lymphatic vessels

PubMed Central

Nurmi, Harri; Voutilainen, Merja H.; Chilov, Dmitri; Park, Jun-Hee; Fang, Shentong; Saarma, Mart; Eichmann, Anne

2017-01-01

The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. PMID:29141865

Tracking transcriptional activities with high-content epifluorescent imaging

NASA Astrophysics Data System (ADS)

Hua, Jianping; Sima, Chao; Cypert, Milana; Gooden, Gerald C.; Shack, Sonsoles; Alla, Lalitamba; Smith, Edward A.; Trent, Jeffrey M.; Dougherty, Edward R.; Bittner, Michael L.

2012-04-01

High-content cell imaging based on fluorescent protein reporters has recently been used to track the transcriptional activities of multiple genes under different external stimuli for extended periods. This technology enhances our ability to discover treatment-induced regulatory mechanisms, temporally order their onsets and recognize their relationships. To fully realize these possibilities and explore their potential in biological and pharmaceutical applications, we introduce a new data processing procedure to extract information about the dynamics of cell processes based on this technology. The proposed procedure contains two parts: (1) image processing, where the fluorescent images are processed to identify individual cells and allow their transcriptional activity levels to be quantified; and (2) data representation, where the extracted time course data are summarized and represented in a way that facilitates efficient evaluation. Experiments show that the proposed procedure achieves fast and robust image segmentation with sufficient accuracy. The extracted cellular dynamics are highly reproducible and sensitive enough to detect subtle activity differences and identify mechanisms responding to selected perturbations. This method should be able to help biologists identify the alterations of cellular mechanisms that allow drug candidates to change cell behavior and thereby improve the efficiency of drug discovery and treatment design.

Head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha): a combination of transmission electron microscopical and immunocytochemical techniques.

PubMed

Liesenjohann, Thilo; Neuhaus, Birger; Schmidt-Rhaesa, Andreas

2006-08-01

The anterior and posterior head sensory organs of Dactylopodola baltica (Macrodasyida, Gastrotricha) were investigated by transmission electron microscopy (TEM). In addition, whole individuals were labeled with phalloidin to mark F-actin and with anti-alpha-tubulin antibodies to mark microtubuli and studied with confocal laser scanning microscopy. Immunocytochemistry reveals that the large number of ciliary processes in the anterior head sensory organ contain F-actin; no signal could be detected for alpha-tubulin. Labeling with anti-alpha-tubulin antibodies revealed that the anterior and posterior head sensory organs are innervated by a common stem of nerves from the lateral nerve cords just anterior of the dorsal brain commissure. TEM studies showed that the anterior head sensory organ is composed of one sheath cell and one sensory cell with a single branching cilium that possesses a basal inflated part and regularly arranged ciliary processes. Each ciliary process contains one central microtubule. The posterior head sensory organ consists of at least one pigmented sheath cell and several probably monociliary sensory cells. Each cilium branches into irregularly arranged ciliary processes. These characters are assumed to belong to the ground pattern of the Gastrotricha. Copyright 2006 Wiley-Liss, Inc.

Pathogenesis of Recalcitrant Chronic Rhinosinusitis: The Emerging Role of Innate Immune Cells.

PubMed

Kong, Il Gyu; Kim, Dae Woo

2018-04-01

Chronic rhinosinusitis (CRS) is a major part of the recalcitrant inflammatory diseases of the upper airway that needs enormous socioeconomic burden. T helper (Th) 2 type immune responses recruiting eosinophils were the most well-known immune players in CRS pathogenesis especially in western countries. By the piling up of a vast amount of researches to elucidate the pathogenic mechanism of CRS recently, heterogeneous inflammatory processes were found to be related to the phenotypes of CRS. Recently more cells other than T cells were in the focus of CRS pathogenesis, such as the epithelial cell, macrophage, innate lymphoid cells, and neutrophils. Here, we reviewed the recent research focusing on the innate immune cells related to CRS pathogenesis.

STUDIES ON ENDOTHELIAL REACTIONS

PubMed Central

Foot, Nathan Chandler

1920-01-01

1. The epithelioid cell is of definitely endothelial origin. 2. The only reliable means of identifying and tracing this cell is, at the present time, a colloidal suspension of carbon, injected intravenously. Benzidine dyes will not accomplish this if used alone. 3. There is little evidence that the local tissue elements take an active part in the process of tubercle formation, until after the lesion is formed; the reaction is, in a sense, exudative, since the lesion is produced from cells which migrate to the site of inflammation. 4. The lymphocyte appears late and is not to be considered as a potential epithelioid cell; its presence in the tubercles is as yet unexplained. PMID:19868458

Solving a mathematical model integrating unequal-area facilities layout and part scheduling in a cellular manufacturing system by a genetic algorithm.

PubMed

Ebrahimi, Ahmad; Kia, Reza; Komijan, Alireza Rashidi

2016-01-01

In this article, a novel integrated mixed-integer nonlinear programming model is presented for designing a cellular manufacturing system (CMS) considering machine layout and part scheduling problems simultaneously as interrelated decisions. The integrated CMS model is formulated to incorporate several design features including part due date, material handling time, operation sequence, processing time, an intra-cell layout of unequal-area facilities, and part scheduling. The objective function is to minimize makespan, tardiness penalties, and material handling costs of inter-cell and intra-cell movements. Two numerical examples are solved by the Lingo software to illustrate the results obtained by the incorporated features. In order to assess the effects and importance of integration of machine layout and part scheduling in designing a CMS, two approaches, sequentially and concurrent are investigated and the improvement resulted from a concurrent approach is revealed. Also, due to the NP-hardness of the integrated model, an efficient genetic algorithm is designed. As a consequence, computational results of this study indicate that the best solutions found by GA are better than the solutions found by B&B in much less time for both sequential and concurrent approaches. Moreover, the comparisons between the objective function values (OFVs) obtained by sequential and concurrent approaches demonstrate that the OFV improvement is averagely around 17 % by GA and 14 % by B&B.

Myeloid derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications

PubMed Central

Diaz-Montero, C. Marcela; Finke, Jim; Montero, Alberto J.

2014-01-01

Immune evasion is a hallmark of cancer. While, there are multiple different mechanisms that cancer cells employ, myeloid deriver suppressor cells (MDSCs) are one of the key drivers of tumor mediated immune evasion. MDSCs begin as myeloid cells recruited to the tumor microenvironment where they are transformed into potent immunosuppressive cells. Our understanding of the clinical relevance of MDSCs in cancer patients, however has significantly lagged behind the preclinical literature in part due to the absence of a cognate molecule present in mice, as well as the considerable heterogeneity of MDSCs. However, if one evaluates the clinical literature through the filter of clinically robust endpoints, such as overall survival, three important phenotypes have emerged: promyelocytic, monocytic, and granulocytic. Based on these studies, MDSCs have clear prognostic importance in multiple solid tumors, and emerging data supports the utility of circulating MDSCs as a predictive marker for cancer immunotherapy, and even as an early leading marker for predicting clinical response to systemic chemotherapy in patients with advanced solid tumors. More recent preclinical data in immunosuppressed murine models suggest that MDSCs play an important role in tumor progression and the metastatic process that is independent of their immunosuppressive properties. Consequently, targeting MDSCs either in combination with cancer immunotherapy or independently as part of an approach to inhibit the metastatic process, appears to be a very clinically promising strategy. We review different approaches to target MDSCs that could potentially be tested in future clinical trials in cancer patients. PMID:24787291

Sense of place and place identity: review of neuroscientific evidence.

PubMed

Lengen, Charis; Kistemann, Thomas

2012-09-01

The aim of this review is to bring the phenomenological sense of place approach together with current results from neuroscience. We searched in neuroscientific literature for ten dimensions which were beforehand identified to be important in a phenomenological sense of place/place identity model: behaviour, body, emotion, attention, perception, memory, orientation, spirituality, meaning/value and culture/sociality. Neuroscience has identified many neurobiological correlates of phenomenological observations concerning sense of place. The human brain comprises specific and specialised structures and processes to perceive, memorise, link, assess and use spatial information. Specific parts (hippocampus, entorhinal, parahippocampal and parietal cortex), subregions (parahippocampal place area, lingual landmark area), and cells (place cells, grid cells, border cells, head direction cells) have been identified, their specific function could be understood and their interaction traced. Neuroscience has provided evidence that place constitutes a distinct dimension in neuronal processing. This reinforces the phenomenological argumentation of human geography and environmental psychology. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vivo biochemistry: quantifying ion and metabolite levels in individual cells or cultures of yeast.

PubMed

Bermejo, Clara; Ewald, Jennifer C; Lanquar, Viviane; Jones, Alexander M; Frommer, Wolf B

2011-08-15

Over the past decade, we have learned that cellular processes, including signalling and metabolism, are highly compartmentalized, and that relevant changes in metabolic state can occur at sub-second timescales. Moreover, we have learned that individual cells in populations, or as part of a tissue, exist in different states. If we want to understand metabolic processes and signalling better, it will be necessary to measure biochemical and biophysical responses of individual cells with high temporal and spatial resolution. Fluorescence imaging has revolutionized all aspects of biology since it has the potential to provide information on the cellular and subcellular distribution of ions and metabolites with sub-second time resolution. In the present review we summarize recent progress in quantifying ions and metabolites in populations of yeast cells as well as in individual yeast cells with the help of quantitative fluorescent indicators, namely FRET metabolite sensors. We discuss the opportunities and potential pitfalls and the controls that help preclude misinterpretation. © The Authors Journal compilation © 2011 Biochemical Society

A wetting and drying scheme for ROMS

USGS Publications Warehouse

Warner, John C.; Defne, Zafer; Haas, Kevin; Arango, Hernan G.

2013-01-01

The processes of wetting and drying have many important physical and biological impacts on shallow water systems. Inundation and dewatering effects on coastal mud flats and beaches occur on various time scales ranging from storm surge, periodic rise and fall of the tide, to infragravity wave motions. To correctly simulate these physical processes with a numerical model requires the capability of the computational cells to become inundated and dewatered. In this paper, we describe a method for wetting and drying based on an approach consistent with a cell-face blocking algorithm. The method allows water to always flow into any cell, but prevents outflow from a cell when the total depth in that cell is less than a user defined critical value. We describe the method, the implementation into the three-dimensional Regional Oceanographic Modeling System (ROMS), and exhibit the new capability under three scenarios: an analytical expression for shallow water flows, a dam break test case, and a realistic application to part of a wetland area along the Georgia Coast, USA.

Bipolar plates for PEM fuel cells

NASA Astrophysics Data System (ADS)

Middelman, E.; Kout, W.; Vogelaar, B.; Lenssen, J.; de Waal, E.

The bipolar plates are in weight and volume the major part of the PEM fuel cell stack, and are also a significant contributor to the stack costs. The bipolar plate is therefore a key component if power density has to increase and costs must come down. Three cell plate technologies are expected to reach targeted cost price levels, all having specific advantages and drawbacks. NedStack has developed a conductive composite materials and a production process for fuel cell plates (bipolar and mono-polar). The material has a high electric and thermal conductivity, and can be processed into bipolar plates by a proprietary molding process. Process cycle time has been reduced to less than 10 s, making the material and process suitable for economical mass production. Other development work to increase material efficiency resulted in thin bipolar plates with integrated cooling channels, and integrated seals, and in two-component bipolar plates. Total thickness of the bipolar plates is now less than 3 mm, and will be reduced to 2 mm in the near future. With these thin integrated plates it is possible to increase power density up to 2 kW/l and 2 kW/kg, while at the same time reducing cost by integrating other functions and less material use.

Initial observation of potential factors involved in the specification process of oral-aboral axis in the sand dollar Scaphechinus mirabilis.

PubMed

Satoh, Kanehide; Kominami, Tetsuya

2008-10-01

To elucidate factors involved in the oral-aboral axis specification, several observations and experiments were undertaken using the sand dollar Scaphechinus mirabilis. Unlike in Strongylcentrotus purpuratus, localization of mitochondria was not detected in unfertilized eggs. After fertilization, however, the bulk of mitochondria became localized to the opposite side of sperm entry. The first cleavage divided this mitochondrial cluster into daughter blastomeres. On the other hand, a second cleavage produced daughter blastomeres containing quite different amounts of mitochondria. To know whether such mitochondrial localization affects the oral-aboral axis specification, 4-cell-stage embryos were separated along the second cleavage plane. Although both half embryos developed into morphologically normal plutei, some differences, such as the number of pigment cells, were noticed between the siblings. In contrast, cell tracing revealed that the first cleavage separated the oral from the aboral part in most cases, indicating that the unequal distribution of mitochondria is not critical for the oral-aboral axis specification. Further, stained and non-stained half embryo fragments were combined. Such combined embryos developed into normal plutei with a single oral-aboral axis. The plane dividing labeled and non-labeled parts were incident, oblique or perpendicular to the median plane of the combined embryo, and the appearance frequencies of those labeling patterns were similar to those obtained by cell tracing in intact embryos. Interestingly, the half fragments derived from embryos inseminated earlier showed a tendency to form the oral part. These suggest that several factors as well as the localized cytoplasmic components would be involved in the specification process of oral-aboral axis.

Fluorescence Live Cell Imaging

PubMed Central

Ettinger, Andreas

2014-01-01

Fluorescence microscopy of live cells has become an integral part of modern cell biology. Fluorescent protein tags, live cell dyes, and other methods to fluorescently label proteins of interest provide a range of tools to investigate virtually any cellular process under the microscope. The two main experimental challenges in collecting meaningful live cell microscopy data are to minimize photodamage while retaining a useful signal-to-noise ratio, and to provide a suitable environment for cells or tissues to replicate physiological cell dynamics. This chapter aims to give a general overview on microscope design choices critical for fluorescence live cell imaging that apply to most fluorescence microscopy modalities, and on environmental control with a focus on mammalian tissue culture cells. In addition, we provide guidance on how to design and evaluate fluorescent protein constructs by spinning disk confocal microscopy. PMID:24974023

Cell fusion in the brain: two cells forward, one cell back.

PubMed

Kemp, Kevin; Wilkins, Alastair; Scolding, Neil

2014-11-01

Adult stem cell populations, notably those which reside in the bone marrow, have been shown to contribute to several neuronal cell types in the rodent and human brain. The observation that circulating bone marrow cells can migrate into the central nervous system and fuse with, in particular, cerebellar Purkinje cells has suggested, at least in part, a potential mechanism behind this process. Experimentally, the incidence of cell fusion in the brain is enhanced with age, radiation exposure, inflammation, chemotherapeutic drugs and even selective damage to the neurons themselves. The presence of cell fusion, shown by detection of increased bi-nucleated neurons, has also been described in a variety of human central nervous system diseases, including both multiple sclerosis and Alzheimer's disease. Accumulating evidence is therefore raising new questions into the biological significance of cell fusion, with the possibility that it represents an important means of cell-mediated neuroprotection or rescue of highly complex neurons that cannot be replaced in adult life. Here, we discuss the evidence behind this phenomenon in the rodent and human brain, with a focus on the subsequent research investigating the physiological mechanisms of cell fusion underlying this process. We also highlight how these studies offer new insights into endogenous neuronal repair, opening new exciting avenues for potential therapeutic interventions against neurodegeneration and brain injury.

Process development and exergy cost sensitivity analysis of a hybrid molten carbonate fuel cell power plant and carbon dioxide capturing process

NASA Astrophysics Data System (ADS)

Mehrpooya, Mehdi; Ansarinasab, Hojat; Moftakhari Sharifzadeh, Mohammad Mehdi; Rosen, Marc A.

2017-10-01

An integrated power plant with a net electrical power output of 3.71 × 105 kW is developed and investigated. The electrical efficiency of the process is found to be 60.1%. The process includes three main sub-systems: molten carbonate fuel cell system, heat recovery section and cryogenic carbon dioxide capturing process. Conventional and advanced exergoeconomic methods are used for analyzing the process. Advanced exergoeconomic analysis is a comprehensive evaluation tool which combines an exergetic approach with economic analysis procedures. With this method, investment and exergy destruction costs of the process components are divided into endogenous/exogenous and avoidable/unavoidable parts. Results of the conventional exergoeconomic analyses demonstrate that the combustion chamber has the largest exergy destruction rate (182 MW) and cost rate (13,100 /h). Also, the total process cost rate can be decreased by reducing the cost rate of the fuel cell and improving the efficiency of the combustion chamber and heat recovery steam generator. Based on the total avoidable endogenous cost rate, the priority for modification is the heat recovery steam generator, a compressor and a turbine of the power plant, in rank order. A sensitivity analysis is done to investigate the exergoeconomic factor parameters through changing the effective parameter variations.

Plating To Reinforce Welded Joints

NASA Technical Reports Server (NTRS)

Otousa, J. E.

1982-01-01

Electrodeposition used to strengthen welded joints gouged, nicked, or suffered other mechanical damage. Plating cell, typically of acrylic plastic such as poly (Methylmetacrylate), is assembled around part to be plated. Areas not to be plated are masked with plater's tape. Weld area is plated in standard nickel-plating process.

Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells

PubMed Central

Brachmann, Saskia M.; Hofmann, Irmgard; Schnell, Christian; Fritsch, Christine; Wee, Susan; Lane, Heidi; Wang, Shaowen; Garcia-Echeverria, Carlos; Maira, Sauveur-Michel

2009-01-01

NVP-BEZ235 is a dual PI3K/mTOR inhibitor currently in phase I clinical trials. We profiled this compound against a panel of breast tumor cell lines to identify the patient populations that would benefit from such treatment. In this setting, NVP-BEZ235 selectively induced cell death in cell lines presenting either HER2 amplification and/or PIK3CA mutation, but not in cell lines with PTEN loss of function or KRAS mutations, for which resistance could be attributed, in part to ERK pathway activity. An in depth analysis of death markers revealed that the cell death observed upon NVP-BEZ235 treatment could be recapitulated with other PI3K inhibitors and that this event is linked to active PARP cleavage indicative of an apoptotic process. Moreover, the effect seemed to be partly independent of the caspase-9 executioner and mitochondrial activated caspases, suggesting an alternate route for apoptosis induction by PI3K inhibitors. Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235. PMID:20007781

DREAMs make plant cells to cycle or to become quiescent.

PubMed

Magyar, Zoltán; Bögre, László; Ito, Masaki

2016-12-01

Cell cycle phase specific oscillation of gene transcription has long been recognized as an underlying principle for ordered processes during cell proliferation. The G1/S-specific and G2/M-specific cohorts of genes in plants are regulated by the E2F and the MYB3R transcription factors. Mutant analysis suggests that activator E2F functions might not be fully required for cell cycle entry. In contrast, the two activator-type MYB3Rs are part of positive feedback loops to drive the burst of mitotic gene expression, which is necessary at least to accomplish cytokinesis. Repressor MYB3Rs act outside the mitotic time window during cell cycle progression, and are important for the shutdown of mitotic genes to impose quiescence in mature organs. The two distinct classes of E2Fs and MYB3Rs together with the RETINOBLATOMA RELATED are part of multiprotein complexes that may be evolutionary related to what is known as DREAM complex in animals. In plants, there are multiple such complexes with distinct compositions and functions that may be involved in the coordinated cell cycle and developmental regulation of E2F targets and mitotic genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo XCT bone characterization of lattice structured implants fabricated by additive manufacturing.

PubMed

Obaton, A-F; Fain, J; Djemaï, M; Meinel, D; Léonard, F; Mahé, E; Lécuelle, B; Fouchet, J-J; Bruno, G

2017-08-01

Several cylindrical specimens and dental implants, presenting diagonal lattice structures with different cell sizes (600, 900 and 1200 μm) were additively manufactured by selective laser melting process. Then they were implanted for two months in a sheep. After removal, they were studied by Archimedes' method as well as X-ray computed tomography in order to assess the penetration of bone into the lattice. We observed that the additive manufactured parts were geometrically conformed to the theoretical specifications. However, several particles were left adhering to the surface of the lattice, thereby partly or entirely obstructing the cells. Nevertheless, bone penetration was clearly visible. We conclude that the 900 μm lattice cell size is more favourable to bone penetration than the 1200 μm lattice cell size, as the bone penetration is 84% for 900 μm against 54% for 1200 μm cell structures. The lower bone penetration value for the 1200 μm lattice cell could possibly be attributed to the short residence time in the sheep. Our results lead to the conclusion that lattice implants additively manufactured by selective laser melting enable better bone integration.

Gene-expression profiles of epithelial cells treated with EMD in vitro: analysis using complementary DNA arrays.

PubMed

Kapferer, I; Schmidt, S; Gstir, R; Durstberger, G; Huber, L A; Vietor, I

2011-02-01

During surgical periodontal treatment, EMD is topically applied in order to facilitate regeneration of the periodontal ligament, acellular cementum and alveolar bone. Suppresion of epithelial down-growth is essential for successful periodontal regeneration; however, the underlying mechanisms of how EMD influences epithelial wound healing are poorly understood. In the present study, the effects of EMD on gene-expression profiling in an epithelial cell line (HSC-2) model were investigated. Gene-expression modifications, determined using a comparative genome-wide expression-profiling strategy, were independently validated by quantitative real-time RT-PCR. Additionally, cell cycle, cell growth and in vitro wound-healing assays were conducted. A set of 43 EMD-regulated genes was defined, which may be responsible for the reduced epithelial down-growth upon EMD application. Gene ontology analysis revealed genes that could be attributed to pathways of locomotion, developmental processes and associated processes such as regulation of cell size and cell growth. Additionally, eight regulated genes have previously been reported to take part in the process of epithelial-to-mesenchymal transition. Several independent experimental assays revealed significant inhibition of cell migration, growth and cell cycle by EMD. The set of EMD-regulated genes identified in this study offers the opportunity to clarify mechanisms underlying the effects of EMD on epithelial cells. Reduced epithelial repopulation of the dental root upon periodontal surgery may be the consequence of reduced migration and cell growth, as well as epithelial-to-mesenchymal transition. © 2010 John Wiley & Sons A/S.

Neil Hayes, M.D., M.P.H., Explains TCGA Findings on GBM Subtypes - TCGA

Cancer.gov

New findings by researchers at UNC Lineberger Comprehensive Cancer Center suggest that the most common form of malignant brain cancer in adults, glioblastoma multiforme (GBM), is probably not a single disease but a set of diseases, each with a distinct underlying molecular disease process. The study was published by Cell Press in the January issue of the journal Cancer Cell and the researchers are part of the The Cancer Genome Atlas.

[Food safety of GMOs].

PubMed

Joudrier, P

2009-01-01

In this presentation, we review the complexity of the different biological events which occur during life cell cycles. Indeed transgenesis is not an unknown event for cells. In the second part of this article, the complex and complete evaluation process destined to assure the food safety of GMOs, before they are released on the market, is describd. Some ansers to questions frequently asked about the GMOs are given. It is concludedthat GMOs are probably more safe than their conventional non-GM counterpart.

Design of Flow Systems for Improved Networking and Reduced Noise in Biomolecular Signal Processing in Biocomputing and Biosensing Applications

PubMed Central

Verma, Arjun; Fratto, Brian E.; Privman, Vladimir; Katz, Evgeny

2016-01-01

We consider flow systems that have been utilized for small-scale biomolecular computing and digital signal processing in binary-operating biosensors. Signal measurement is optimized by designing a flow-reversal cuvette and analyzing the experimental data to theoretically extract the pulse shape, as well as reveal the level of noise it possesses. Noise reduction is then carried out numerically. We conclude that this can be accomplished physically via the addition of properly designed well-mixing flow-reversal cell(s) as an integral part of the flow system. This approach should enable improved networking capabilities and potentially not only digital but analog signal-processing in such systems. Possible applications in complex biocomputing networks and various sense-and-act systems are discussed. PMID:27399702

Determination of the robot location in a workcell of a flexible production line

NASA Astrophysics Data System (ADS)

Banas, W.; Sekala, A.; Gwiazda, A.; Foit, K.; Hryniewicz, P.; Kost, G.

2015-11-01

Location of components of a manufacturing cell is apparently an easy task but even during the constructing of a manufacturing cell, in which is planned a production of one, simple component it is necessary, among others, to check access to all required points. The robot in a manufacturing cell must handle both machine tools located in a manufacturing cell and parts store (input and output one). It handles also transport equipment and auxiliary stands. Sometimes, during the design phase, the changes of robot location are necessary due to the limitation of access to its required working positions. Often succeeding changes of a manufacturing cell configuration are realized. They occur at the stages of visualization and simulation of robot program functioning. In special cases, it is even necessary to replace the planned robot with a robot of greater range or of a different configuration type. This article presents and describes the parameters and components which should be taken into consideration during designing robotised manufacturing cells. The main idea bases on application of advanced engineering programs to adding the designing process. Using this approach it could be possible to present the designing process of an exemplar flexible manufacturing cell intended to manufacture two similar components. The proposed model of such designed manufacturing cell could be easily extended to the manufacturing cell model in which it is possible to produce components belonging the one technological group of chosen similarity level. In particular, during the design process, one should take into consideration components which limit the ability of robot foundation. It is also important to show the method of determining the best location of robot foundation. The presented design method could also support the designing process of other robotised manufacturing cells.

Theory and applications for optimization of every part of a photovoltaic system

NASA Technical Reports Server (NTRS)

Redfield, D.

1978-01-01

A general method is presented for quantitatively optimizing the design of every part and fabrication step of an entire photovoltaic system, based on the criterion of minimum cost/Watt for the system output power. It is shown that no element or process step can be optimized properly by considering only its own cost and performance. Moreover, a fractional performance loss at any fabrication step within the cell or array produces the same fractional increase in the cost/Watt of the entire array, but not of the full system. One general equation is found to be capable of optimizing all parts of a system, although the cell and array steps are basically different from the power-handling elements. Applications of this analysis are given to show (1) when Si wafers should be cut to increase their packing fraction; and (2) what the optimum dimensions for solar cell metallizations are. The optimum shadow fraction of the fine grid is shown to be independent of metal cost and resistivity as well as cell size. The optimum thicknesses of both the fine grid and the bus bar are substantially greater than the values in general use, and the total array cost has a major effect on these values. By analogy, this analysis is adaptable to other solar energy systems.

Immunocytochemical distribution of glial fibrillary acidic protein in the central nervous system of the Japanese quail (Coturnix coturnix japonica).

PubMed

Cameron-Curry, P; Aste, N; Viglietti-Panzica, C; Panzica, G C

1991-01-01

In the present study we detailed the distribution of GFAP-immunopositive structures within the central nervous system of the Japanese quail. Different fixation and embedding procedures were applied. The best results were obtained on frozen cryostatic sections from freshly dissected brains subsequently fixed by a short immersion in cold acetone. Immunopositive structures were observed both with immunofluorescence, and with immunoperoxidase methods. Immunoreactive cell bodies and processes were observed within the whole central nervous system, and different cell types can be identified on the basis of their topographical location and morphology. A first class of astrocytes is composed of intensely stained unipolar cells lining the inner surface of the pia mater and the large blood vessels. A second type is represented by multipolar astrocytes of variable size, provided with an irregular cell body. The last type is represented by similar elements, showing an immunonegative cell body, that can be identified only by the presence of converging processes. These three types of cells, and several isolated processes, show a differential distribution within the quail central nervous system, both in the grey and in the white matter. Present results suggest that GFAP may represent a good marker for at least part of the astroglial population in quail.

Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara

PubMed Central

Jordan, Ingo; Lohr, Verena; Genzel, Yvonne; Reichl, Udo; Sandig, Volker

2013-01-01

The production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. To replace this logistically demanding substrate, we created continuous anatine suspension cell lines (CR and CR.pIX), developed chemically-defined media, and established production processes for different vaccine viruses. One of the processes investigated in greater detail was developed for modified vaccinia virus Ankara (MVA). MVA is highly attenuated for human recipients and an efficient vector for reactogenic expression of foreign genes. Because direct cell-to-cell spread is one important mechanism for vaccinia virus replication, cultivation of MVA in bioreactors is facilitated if cell aggregates are induced after infection. This dependency may be the mechanism behind our observation that a novel viral genotype (MVA-CR) accumulates with serial passage in suspension cultures. Sequencing of a major part of the genomic DNA of the new strain revealed point mutations in three genes. We hypothesize that these changes confer an advantage because they may allow a greater fraction of MVA-CR viruses to escape the host cells for infection of distant targets. Production and purification of MVA-based vaccines may be simplified by this combination of designed avian cell line, chemically defined media and the novel virus strain. PMID:27694766

Elements in the Development of a Production Process for Modified Vaccinia Virus Ankara.

PubMed

Jordan, Ingo; Lohr, Verena; Genzel, Yvonne; Reichl, Udo; Sandig, Volker

2013-11-01

The production of several viral vaccines depends on chicken embryo fibroblasts or embryonated chicken eggs. To replace this logistically demanding substrate, we created continuous anatine suspension cell lines (CR and CR.pIX), developed chemically-defined media, and established production processes for different vaccine viruses. One of the processes investigated in greater detail was developed for modified vaccinia virus Ankara (MVA). MVA is highly attenuated for human recipients and an efficient vector for reactogenic expression of foreign genes. Because direct cell-to-cell spread is one important mechanism for vaccinia virus replication, cultivation of MVA in bioreactors is facilitated if cell aggregates are induced after infection. This dependency may be the mechanism behind our observation that a novel viral genotype (MVA-CR) accumulates with serial passage in suspension cultures. Sequencing of a major part of the genomic DNA of the new strain revealed point mutations in three genes. We hypothesize that these changes confer an advantage because they may allow a greater fraction of MVA-CR viruses to escape the host cells for infection of distant targets. Production and purification of MVA-based vaccines may be simplified by this combination of designed avian cell line, chemically defined media and the novel virus strain.

Oxysterol-EBI2 signaling in immune regulation and viral infection.

PubMed

Daugvilaite, Viktorija; Arfelt, Kristine Niss; Benned-Jensen, Tau; Sailer, Andreas W; Rosenkilde, Mette M

2014-07-01

The seven transmembrane G protein-coupled receptor Epstein-Barr virus (EBV) induced gene 2 (EBI2; also known as GPR183) was identified in 1993 on the basis of its substantial upregulation in EBV-infected cells. It is primarily expressed in lymphoid cells; most abundantly in B cells. EBI2 is central for the positioning of B cells within the lymphoid organs, a process that is regulated in part by a chemotactic gradient formed by the endogenous lipid agonists, and in part by a fine-tuned regulation of EBI2 cell surface expression. The most potent endogenous EBI2 agonist is 7α, 25-dihydroxyxcholesterol (7α,25-OHC), yet many structurally related oxysterols can bind to an EBI2 pocket that is defined by the upper parts of the transmembrane helices and extracellular receptor regions. EBI2 signals via Gαi, as well as via G protein-independent pathways like β-arrestin recruitment. The concerted action of these pathways leads to cell migration. By genetically interfering with its up- and downregulation, EBI2 was also recently shown to induce cell proliferation, an action that could be inhibited by small molecule antagonists. Here, we focus on the oxysterol-EBI2 axis in immune control, including its role in the EBV life cycle. We also summarize the structural and functional properties of EBI2 interaction with oxysterol agonists and small molecule antagonists and discuss EBI2 as therapeutic target for diseases of the immune system. © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monitoring Photosynthesis in Individual Cells of Synechocystis sp. PCC 6803 on a Picosecond Timescale

PubMed Central

Krumova, S.B.; Laptenok, S.P.; Borst, J.W.; Ughy, B.; Gombos, Z.; Ajlani, G.; van Amerongen, H.

2010-01-01

Picosecond fluorescence kinetics of wild-type (WT) and mutant cells of Synechocystis sp. PCC 6803, were studied at the ensemble level with a streak-camera and at the cell level using fluorescence-lifetime-imaging microscopy (FLIM). The FLIM measurements are in good agreement with the ensemble measurements, but they (can) unveil variations between and within cells. The BE mutant cells, devoid of photosystem II (PSII) and of the light-harvesting phycobilisomes, allowed the study of photosystem I (PSI) in vivo for the first time, and the observed 6-ps equilibration process and 25-ps trapping process are the same as found previously for isolated PSI. No major differences are detected between different cells. The PAL mutant cells, devoid of phycobilisomes, show four lifetimes: ∼20 ps (PSI and PSII), ∼80 ps, ∼440 ps, and 2.8 ns (all due to PSII), but not all cells are identical and variations in the kinetics are traced back to differences in the PSI/PSII ratio. Finally, FLIM measurements on WT cells reveal that in some cells or parts of cells, phycobilisomes are disconnected from PSI/PSII. It is argued that the FLIM setup used can become instrumental in unraveling photosynthetic regulation mechanisms in the future. PMID:20858447

Comparison and optimization of machine learning methods for automated classification of circulating tumor cells.

PubMed

Lannin, Timothy B; Thege, Fredrik I; Kirby, Brian J

2016-10-01

Advances in rare cell capture technology have made possible the interrogation of circulating tumor cells (CTCs) captured from whole patient blood. However, locating captured cells in the device by manual counting bottlenecks data processing by being tedious (hours per sample) and compromises the results by being inconsistent and prone to user bias. Some recent work has been done to automate the cell location and classification process to address these problems, employing image processing and machine learning (ML) algorithms to locate and classify cells in fluorescent microscope images. However, the type of machine learning method used is a part of the design space that has not been thoroughly explored. Thus, we have trained four ML algorithms on three different datasets. The trained ML algorithms locate and classify thousands of possible cells in a few minutes rather than a few hours, representing an order of magnitude increase in processing speed. Furthermore, some algorithms have a significantly (P < 0.05) higher area under the receiver operating characteristic curve than do other algorithms. Additionally, significant (P < 0.05) losses to performance occur when training on cell lines and testing on CTCs (and vice versa), indicating the need to train on a system that is representative of future unlabeled data. Optimal algorithm selection depends on the peculiarities of the individual dataset, indicating the need of a careful comparison and optimization of algorithms for individual image classification tasks. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

Expression of MIF and CD74 in leukemic cell lines: correlation to DR expression destiny.

PubMed

Georgouli, Mirella; Papadimitriou, Lina; Glymenaki, Maria; Patsaki, Valia; Athanassakis, Irene

2016-06-01

Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein, which apart from its role as a chaperone dedicated to MHCII molecules, is known to be a high-affinity receptor for macrophage migration inhibitory factor (MIF). The present study aimed to define the roles of CD74 and MIF in the immune surveillance escape process. Towards this direction, the cell lines HL-60, Raji, K562 and primary pre-B leukemic cells were examined for expression and secretion of MIF. Flow cytometry analysis detected high levels of MIF and intracellular/membrane CD74 expression in all leukemic cells tested, while MIF secretion was shown to be inversely proportional to intracellular HLA-DR (DR) expression. In the MHCII-negative cells, IFN-γ increased MIF expression and induced its secretion in HL-60 and K562 cells, respectively. In K562 cells, CD74 (Iip33Iip35) was shown to co-precipitate with HLA-DOβ (DOβ), inhibiting thus MIF or DR binding. Induced expression of DOα in K562 (DOα-DOβ+) cells in different transfection combinations decreased MIF expression and secretion, while increasing surface DR expression. Thus, MIF could indeed be part of the antigen presentation process.

Potential radiological impact of tornadoes on the safety of Nuclear Fuel Services' West Valley Fuel Reprocessing Plant. Volume I. Tornado effects on head-end cell airflow

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

Holloway, L.J.; Andrae, R.W.

1981-09-01

This report describes results of a parametric study of the impacts of a tornado-generated depressurization on airflow in the contaminated process cells within the presently inoperative Nuclear Fuel Services fuel reprocessing facility near West Valley, NY. The study involved the following tasks: (1) mathematical modeling of installed ventilation and abnormal exhaust pathways from the cells and prediction of tornado-induced airflows in these pathways; (2) mathematical modeling of individual cell flow characteristics and prediction of in-cell velocities induced by flows from step 1; and (3) evaluation of the results of steps 1 and 2 to determine whether any of the pathwaysmore » investigated have the potential for releasing quantities of radioactively contaminated air from the main process cells. The study has concluded that in the event of a tornado strike, certain pathways from the cells have the potential to release radioactive materials of the atmosphere. Determination of the quantities of radioactive material released from the cells through pathways identified in step 3 is presented in Part II of this report.« less

Defense Waste Processing Facility Nitric- Glycolic Flowsheet Chemical Process Cell Chemistry: Part 2

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

Zamecnik, J.; Edwards, T.

The conversions of nitrite to nitrate, the destruction of glycolate, and the conversion of glycolate to formate and oxalate were modeled for the Nitric-Glycolic flowsheet using data from Chemical Process Cell (CPC) simulant runs conducted by Savannah River National Laboratory (SRNL) from 2011 to 2016. The goal of this work was to develop empirical correlation models to predict these values from measureable variables from the chemical process so that these quantities could be predicted a-priori from the sludge or simulant composition and measurable processing variables. The need for these predictions arises from the need to predict the REDuction/OXidation (REDOX) statemore » of the glass from the Defense Waste Processing Facility (DWPF) melter. This report summarizes the work on these correlations based on the aforementioned data. Previous work on these correlations was documented in a technical report covering data from 2011-2015. This current report supersedes this previous report. Further refinement of the models as additional data are collected is recommended.« less

Mass Spectrometry of Polymer Electrolyte Membrane Fuel Cells.

PubMed

Johánek, Viktor; Ostroverkh, Anna; Fiala, Roman; Rednyk, Andrii; Matolín, Vladimír

2016-01-01

The chemical analysis of processes inside fuel cells under operating conditions in either direct or inverted (electrolysis) mode and their correlation with potentiostatic measurements is a crucial part of understanding fuel cell electrochemistry. We present a relatively simple yet powerful experimental setup for online monitoring of the fuel cell exhaust (of either cathode or anode side) downstream by mass spectrometry. The influence of a variety of parameters (composition of the catalyst, fuel type or its concentration, cell temperature, level of humidification, mass flow rate, power load, cell potential, etc.) on the fuel cell operation can be easily investigated separately or in a combined fashion. We demonstrate the application of this technique on a few examples of low-temperature (70°C herein) polymer electrolyte membrane fuel cells (both alcohol- and hydrogen-fed) subjected to a wide range of conditions.

Mass Spectrometry of Polymer Electrolyte Membrane Fuel Cells

PubMed Central

Ostroverkh, Anna; Fiala, Roman; Rednyk, Andrii; Matolín, Vladimír

2016-01-01

The chemical analysis of processes inside fuel cells under operating conditions in either direct or inverted (electrolysis) mode and their correlation with potentiostatic measurements is a crucial part of understanding fuel cell electrochemistry. We present a relatively simple yet powerful experimental setup for online monitoring of the fuel cell exhaust (of either cathode or anode side) downstream by mass spectrometry. The influence of a variety of parameters (composition of the catalyst, fuel type or its concentration, cell temperature, level of humidification, mass flow rate, power load, cell potential, etc.) on the fuel cell operation can be easily investigated separately or in a combined fashion. We demonstrate the application of this technique on a few examples of low-temperature (70°C herein) polymer electrolyte membrane fuel cells (both alcohol- and hydrogen-fed) subjected to a wide range of conditions. PMID:28042492

Improved FCG-1 cell technology

NASA Astrophysics Data System (ADS)

Breault, R. D.; Congdon, J. V.; Coykendall, R. D.; Luoma, W. L.

1980-10-01

Fuel cell performance in the ribbed substrate cell configuration consistent with that projected for a commercial power plant is demonstrated. Tests were conducted on subscale cells and on two 20 cell stacks of 4.8 MW demonstrator size cell components. These tests evaluated cell stack materials, processes, components, and assembly configurations. The first task was to conduct a component development effort to introduce improvements in 3.7 square foot, ribbed substrate acid cell repeating parts which represented advances in performance, function, life, and lower cost for application in higher pressure and temperature power plants. Specific areas of change were the electrode substrate, catalyst, matrix, seals, separator plates, and coolers. Full sized ribbed substrate stack components incorporating more stable materials were evaluated at increased pressure (93 psia) and temperature (405 F) conditions. Two 20 cell stacks with a 3.7 square feet, ribbed substrate cell configuration were tested.

Mitosis.

ERIC Educational Resources Information Center

Henderson, Paula

Cytology is the subject that is dealt with in this autoinstructional program. The process to be understood by secondary school students who are taking biology is mitosis. The material is presented to be adequate for achievers at the middle level. Knowledge of the structure of the DNA molecule and of the parts of the cell are considered as…

Recent advances in synthetic biology of cyanobacteria.

PubMed

Sengupta, Annesha; Pakrasi, Himadri B; Wangikar, Pramod P

2018-05-09

Cyanobacteria are attractive hosts that can be engineered for the photosynthetic production of fuels, fine chemicals, and proteins from CO 2 . Moreover, the responsiveness of these photoautotrophs towards different environmental signals, such as light, CO 2 , diurnal cycle, and metals make them potential hosts for the development of biosensors. However, engineering these hosts proves to be a challenging and lengthy process. Synthetic biology can make the process of biological engineering more predictable through the use of standardized biological parts that are well characterized and tools to assemble them. While significant progress has been made with model heterotrophic organisms, many of the parts and tools are not portable in cyanobacteria. Therefore, efforts are underway to develop and characterize parts derived from cyanobacteria. In this review, we discuss the reported parts and tools with the objective to develop cyanobacteria as cell factories or biosensors. We also discuss the issues related to characterization, tunability, portability, and the need to develop enabling technologies to engineer this "green" chassis.

Regulatory assembly of the vacuolar proton pump VoV1-ATPase in yeast cells by FLIM-FRET

NASA Astrophysics Data System (ADS)

Ernst, Stefan; Batisse, Claire; Zarrabi, Nawid; Böttcher, Bettina; Börsch, Michael

2010-02-01

We investigate the reversible disassembly of VOV1-ATPase in life yeast cells by time resolved confocal FRET imaging. VOV1-ATPase in the vacuolar membrane pumps protons from the cytosol into the vacuole. VOV1-ATPase is a rotary biological nanomotor driven by ATP hydrolysis. The emerging proton gradient is used for secondary transport processes as well as for pH and Ca2+ homoeostasis in the cell. The activity of the VOV1-ATPase is regulated through assembly / disassembly processes. During starvation the two parts of VOV1-ATPase start to disassemble. This process is reversed after addition of glucose. The exact mechanisms are unknown. To follow the disassembly / reassembly in vivo we tagged two subunits C and E with different fluorescent proteins. Cellular distributions of C and E were monitored using a duty cycle-optimized alternating laser excitation scheme (DCO-ALEX) for time resolved confocal FRET-FLIM measurements.

I-PFO: the new technology for simple and flexible implementation of high productive on-the-fly remote processes

NASA Astrophysics Data System (ADS)

Müllegger, Andreas; Ryba, Tracey

2017-02-01

Standardized production systems which can be implemented, programmed, maintained and sourced in a simple and efficient way are key for a successful global production of automobiles or related parts at component suppliers. This is also valid for systems, which are built by laser based processes. One of the key applications is remote laser welding (RLW) of "Body in White" (BIW) parts (such as hang-on parts, B-Pillars, side frames, etc.), but also builtin components (such as car seats, batteries, etc.). The majority of RLW applications are based on the implementation of a 3-D scanner optic (e.g. the PFO 3D from TRUMPF) which positions the laser beam on the various component surfaces to be welded. Over the past 10 years it has been proven that the most efficient way to build up the RLW process is to have a system where an industrial robot and a scanner optic are combined in one production cell. They usually cooperate within an "On-The-Fly" (OTF) process as this ensures minimum cycle times. Until now there are several technologies on the market which can coordinate both the robot and scanner in the OTF mode. But none of them meet all requirements of global standardized production solutions. With the introduction of the I-PFO (Intelligent Programmable Focusing Optics) technology the situation has changed. It is now possible to program or adopt complex remote processes in a fast and easy way by the "Teach-in" function via the robot teach pendant. Additionally a 3D offline designer software is an option for this system. It automatically creates the ideal remote process based on the part, fixture, production cell and required process parameters. The I-PFO technology doesn't need additional hardware due to the fact that it runs on the controller within the PFO 3D. Furthermore it works together with different types of industrial robots (e.g. ABB, Fanuc and KUKA) which allow highest flexibility for the production planning phase. Finally a single TRUMPF laser source can supply up to six I-PFOs. This guarantees maximum beam-on time at the production line. Within this report the concept of the I-PFO technology (with mentioned functions) is described and is compared to the other existing ways for Remote Laser processing.

Single cell integration of animate form, motion and location in the superior temporal cortex of the macaque monkey.

PubMed

Jellema, Tjeerd; Maassen, Gerard; Perrett, David I

2004-07-01

This study investigated the cellular mechanisms in the anterior part of the superior temporal sulcus (STSa) that underlie the integration of different features of the same visually perceived animate object. Three visual features were systematically manipulated: form, motion and location. In 58% of a population of cells selectively responsive to the sight of a walking agent, the location of the agent significantly influenced the cell's response. The influence of position was often evident in intricate two- and three-way interactions with the factors form and/or motion. For only one of the 31 cells tested, the response could be explained by just a single factor. For all other cells at least two factors, and for half of the cells (52%) all three factors, played a significant role in controlling responses. Our findings support a reformulation of the Ungerleider and Mishkin model, which envisages a subdivision of the visual processing into a ventral 'what' and a dorsal 'where' stream. We demonstrated that at least part of the temporal cortex ('what' stream) makes ample use of visual spatial information. Our findings open up the prospect of a much more elaborate integration of visual properties of animate objects at the single cell level. Such integration may support the comprehension of animals and their actions.

MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages.

PubMed

Curtale, Graziella

2018-02-08

Innate immune cells form an integrative component of the tumor microenvironment (TME), which can control or prevent tumor initiation and progression, due to the simultaneous processing of both anti- and pro-growth signals. This decision-making process is a consequence of gene expression changes, which are in part dependent on post-transcriptional regulatory mechanisms. In this context, microRNAs have been shown to regulate both recruitment and activation of specific tumor-associated immune cells in the TME. This review aims to describe the most important microRNAs that target cancer-related innate immune pathways. The role of exosomal microRNAs in tumor progression and microRNA-based therapeutic strategies are also discussed.

The Light-Induced Field-Effect Solar Cell Concept - Perovskite Nanoparticle Coating Introduces Polarization Enhancing Silicon Cell Efficiency.

PubMed

Wang, Yusheng; Xia, Zhouhui; Liu, Lijia; Xu, Weidong; Yuan, Zhongcheng; Zhang, Yupeng; Sirringhaus, Henning; Lifshitz, Yeshayahu; Lee, Shui-Tong; Bao, Qiaoliang; Sun, Baoquan

2017-05-01

Solar cell generates electrical energy from light one via pulling excited carrier away under built-in asymmetry. Doped semiconductor with antireflection layer is general strategy to achieve this including crystalline silicon (c-Si) solar cell. However, loss of extra energy beyond band gap and light reflection in particular wavelength range is known to hinder the efficiency of c-Si cell. Here, it is found that part of short wavelength sunlight can be converted into polarization electrical field, which strengthens asymmetry in organic-c-Si heterojunction solar cell through molecule alignment process. The light harvested by organometal trihalide perovskite nanoparticles (NPs) induces molecular alignment on a conducting polymer, which generates positive electrical surface field. Furthermore, a "field-effect solar cell" is successfully developed and implemented by combining perovskite NPs with organic/c-Si heterojunction associating with light-induced molecule alignment, which achieves an efficiency of 14.3%. In comparison, the device with the analogous structure without perovskite NPs only exhibits an efficiency of 12.7%. This finding provides a novel concept to design solar cell by sacrificing part of sunlight to provide "extra" asymmetrical field continuously as to drive photogenerated carrier toward respective contacts under direct sunlight. Moreover, it also points out a method to combine promising perovskite material with c-Si solar cell. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Material challenges for solar cells in the twenty-first century: directions in emerging technologies.

PubMed

Almosni, Samy; Delamarre, Amaury; Jehl, Zacharie; Suchet, Daniel; Cojocaru, Ludmila; Giteau, Maxime; Behaghel, Benoit; Julian, Anatole; Ibrahim, Camille; Tatry, Léa; Wang, Haibin; Kubo, Takaya; Uchida, Satoshi; Segawa, Hiroshi; Miyashita, Naoya; Tamaki, Ryo; Shoji, Yasushi; Yoshida, Katsuhisa; Ahsan, Nazmul; Watanabe, Kentaro; Inoue, Tomoyuki; Sugiyama, Masakazu; Nakano, Yoshiaki; Hamamura, Tomofumi; Toupance, Thierry; Olivier, Céline; Chambon, Sylvain; Vignau, Laurence; Geffroy, Camille; Cloutet, Eric; Hadziioannou, Georges; Cavassilas, Nicolas; Rale, Pierre; Cattoni, Andrea; Collin, Stéphane; Gibelli, François; Paire, Myriam; Lombez, Laurent; Aureau, Damien; Bouttemy, Muriel; Etcheberry, Arnaud; Okada, Yoshitaka; Guillemoles, Jean-François

2018-01-01

Photovoltaic generation has stepped up within the last decade from outsider status to one of the important contributors of the ongoing energy transition, with about 1.7% of world electricity provided by solar cells. Progress in materials and production processes has played an important part in this development. Yet, there are many challenges before photovoltaics could provide clean, abundant, and cheap energy. Here, we review this research direction, with a focus on the results obtained within a Japan-French cooperation program, NextPV, working on promising solar cell technologies. The cooperation was focused on efficient photovoltaic devices, such as multijunction, ultrathin, intermediate band, and hot-carrier solar cells, and on printable solar cell materials such as colloidal quantum dots.

Full Sputtering Deposition of Thin Film Solar Cells: A Way of Achieving High Efficiency Sustainable Tandem Cells?

NASA Astrophysics Data System (ADS)

Vilcot, J.-P.; Ayachi, B.; Aviles, T.; Miska, P.

2017-11-01

In the first part of this paper, we will show that a sputtering-based fabrication process exhibiting a low environmental footprint has been developed for the fabrication of copper indium gallium selenide (CIGS) absorbing material. Its originality lies in using room temperature sputtering in a pulsed—direct current mode of a single quaternary target followed by a post-anneal. At any stage of the process, selenium or sulfur atmosphere is used. Inert gas is used, respectively argon and a forming gas, for the deposition and annealing step, respectively. CIGS cells have been fabricated using such an absorbing layer. They exhibit an efficiency close to 12%. A tandem cell approach, using a thin film technology in conjunction with the well-established Si technology, is a promising technique, achieving cells with 30%, and higher, efficiency. Such cells are awaited, jointly with a stronger implementation of low environmental footprint technologies, as a vision for 2030. In the first section, sputtering technique has shown its ability to be developed in such a way achieving an environmentally friendly process that can be moreover compatible to be co-integrated with, for example, Si technology. In a second section, we will present a prospective discussion on the materials that can be applied to produce a sustainable approach for such a tandem cell configuration.

A sacrificial process for fabrication of biodegradable polymer membranes with submicron thickness.

PubMed

Beardslee, Luke A; Stolwijk, Judith; Khaladj, Dimitrius A; Trebak, Mohamed; Halman, Justin; Torrejon, Karen Y; Niamsiri, Nuttawee; Bergkvist, Magnus

2016-08-01

A new sacrificial molding process using a single mask has been developed to fabricate ultrathin 2-dimensional membranes from several biocompatible polymeric materials. The fabrication process is similar to a sacrificial microelectromechanical systems (MEMS) process flow, where a mold is created from a material that can be coated with a biodegradable polymer and subsequently etched away, leaving behind a very thin polymer membrane. In this work, two different sacrificial mold materials, silicon dioxide (SiO2 ) and Liftoff Resist (LOR) were used. Three different biodegradable materials; polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and polyglycidyl methacrylate (PGMA), were chosen as model polymers. We demonstrate that this process is capable of fabricating 200-500 nm thin, through-hole polymer membranes with various geometries, pore-sizes and spatial features approaching 2.5 µm using a mold fabricated via a single contact photolithography exposure. In addition, the membranes can be mounted to support rings made from either SU8 or PCL for easy handling after release. Cell culture compatibility of the fabricated membranes was evaluated with human dermal microvascular endothelial cells (HDMECs) seeded onto the ultrathin porous membranes, where the cells grew and formed confluent layers with well-established cell-cell contacts. Furthermore, human trabecular meshwork cells (HTMCs) cultured on these scaffolds showed similar proliferation as on flat PCL substrates, further validating its compatibility. All together, these results demonstrated the feasibility of our sacrificial fabrication process to produce biocompatible, ultra-thin membranes with defined microstructures (i.e., pores) with the potential to be used as substrates for tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1192-1201, 2016. © 2015 Wiley Periodicals, Inc.

Caspase inhibitors affect the kinetics and dimensions of tracheary elements in xylogenic Zinnia (Zinnia elegans) cell cultures.

PubMed

Twumasi, Peter; Iakimova, Elena T; Qian, Tian; van Ieperen, Wim; Schel, Jan H N; Emons, Anne Mie C; van Kooten, Olaf; Woltering, Ernst J

2010-08-06

The xylem vascular system is composed of fused dead, hollow cells called tracheary elements (TEs) that originate through trans-differentiation of root and shoot cambium cells. TEs undergo autolysis as they differentiate and mature. The final stage of the formation of TEs in plants is the death of the involved cells, a process showing some similarities to programmed cell death (PCD) in animal systems. Plant proteases with functional similarity to proteases involved in mammalian apoptotic cell death (caspases) are suggested as an integral part of the core mechanism of most PCD responses in plants, but participation of plant caspase-like proteases in TE PCD has not yet been documented. Confocal microscopic images revealed the consecutive stages of TE formation in Zinnia cells during trans-differentiation. Application of the caspase inhibitors Z-Asp-CH2-DCB, Ac-YVAD-CMK and Ac-DEVD-CHO affected the kinetics of formation and the dimensions of the TEs resulting in a significant delay of TE formation, production of larger TEs and in elimination of the 'two-wave' pattern of TE production. DNA breakdown and appearance of TUNEL-positive nuclei was observed in xylogenic cultures and this was suppressed in the presence of caspase inhibitors. To the best of our knowledge this is the first report showing that caspase inhibitors can modulate the process of trans-differentiation in Zinnia xylogenic cell cultures. As caspase inhibitors are closely associated with cell death inhibition in a variety of plant systems, this suggests that the altered TE formation results from suppression of PCD. The findings presented here are a first step towards the use of appropriate PCD signalling modulators or related molecular genetic strategies to improve the hydraulic properties of xylem vessels in favour of the quality and shelf life of plants or plant parts.

Production of erythrocytes from directly isolated or Delta1 Notch ligand expanded CD34+ hematopoietic progenitor cells: process characterization, monitoring and implications for manufacture.

PubMed

Glen, Katie E; Workman, Victoria L; Ahmed, Forhad; Ratcliffe, Elizabeth; Stacey, Adrian J; Thomas, Robert J

2013-09-01

Economic ex vivo manufacture of erythrocytes at 10(12) cell doses requires an efficiently controlled bio-process capable of extensive proliferation and high terminal density. High-resolution characterization of the process would identify production strategies for increased efficiency, monitoring and control. CD34(+) cord blood cells or equivalent cells that had been pre-expanded for 7 days with Delta1 Notch ligand were placed in erythroid expansion and differentiation conditions in a micro-scale ambr suspension bioreactor. Multiple culture parameters were varied, and phenotype markers and metabolites measured to identify conserved trends and robust monitoring markers. The cells exhibited a bi-modal erythroid differentiation pattern with an erythroid marker peak after 2 weeks and 3 weeks of culture; differentiation was comparatively weighted toward the second peak in Delta1 pre-expanded cells. Both differentiation events were strengthened by omission of stem cell factor and dexamethasone. The cumulative cell proliferation and death, or directly measured CD45 expression, enabled monitoring of proliferative rate of the cells. The metabolic activities of the cultures (glucose, glutamine and ammonia consumption or production) were highly variable but exhibited systematic change synchronized with the change in differentiation state. Erythroid differentiation chronology is partly determined by the heterogeneous CD34(+) progenitor compartment with implications for input control; Delta1 ligand-mediated progenitor culture can alter differentiation profile with control benefits for engineering production strategy. Differentiation correlated changes in cytokine response, markers and metabolic state will enable scientifically designed monitoring and timing of manufacturing process steps. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Fast epi-detected broadband multiplex CARS and SHG imaging of mouse skull cells

PubMed Central

Capitaine, Erwan; Moussa, Nawel Ould; Louot, Christophe; Bardet, Sylvia M.; Kano, Hideaki; Duponchel, Ludovic; Lévêque, Philippe; Couderc, Vincent; Leproux, Philippe

2017-01-01

We present a bimodal imaging system able to obtain epi-detected mutiplex coherent anti-Stokes Raman scattering (M-CARS) and second harmonic generation (SHG) signals coming from biological samples. We studied a fragment of mouse parietal bone and could detect broadband anti-Stokes and SHG responses originating from bone cells and collagen respectively. In addition we compared two post-processing methods to retrieve the imaginary part of the third-order nonlinear susceptibility related to the spontaneous Raman scattering. PMID:29359100

Animal Models of Atherosclerosis

PubMed Central

Getz, Godfrey S.; Reardon, Catherine A.

2012-01-01

Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

A universal piezo-driven ultrasonic cell microinjection system.

PubMed

Huang, Haibo; Mills, James K; Lu, Cong; Sun, Dong

2011-08-01

Over the past decade, the rapid development of biotechnologies such as gene injection, in-vitro fertilization, intracytoplasmic sperm injection (ICSI) and drug development have led to great demand for highly automated, high precision equipment for microinjection. Recently a new cell injection technology using piezo-driven pipettes with a very small mercury column was proposed and successfully applied in ICSI to a variety of mammal species. Although this technique significantly improves the survival rates of the ICSI process, shortcomings due to the toxicity of mercury and damage to the cell membrane due to large lateral tip oscillations of the injector pipette may limit its application. In this paper, a new cell injection system for automatic batch injection of suspended cells is developed. A new design of the piezo-driven cell injector is proposed for automated suspended cell injection. This new piezo-driven cell injector design relocates the piezo oscillation actuator to the injector pipette which eliminates the vibration effect on other parts of the micromanipulator. A small piezo stack is sufficient to perform the cell injection process. Harmful lateral tip oscillations of the injector pipette are reduced substantially without the use of a mercury column. Furthermore, ultrasonic vibration micro-dissection (UVM) theory is utilized to analyze the piezo-driven cell injection process, and the source of the lateral oscillations of the injector pipette is investigated. From preliminary experiments of cell injection of a large number of zebrafish embryos (n = 200), the injector pipette can easily pierce through the cell membrane at a low injection speed and almost no deformation of the cell wall, and with a high success rate(96%) and survival rate(80.7%) This new injection approach shows good potential for precision injection with less damage to the injected cells.

Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

PubMed

Bevins, Charles L; Salzman, Nita H

2011-05-01

Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

Retracing in correlative light electron microscopy: where is my object of interest?

PubMed

Hodgson, Lorna; Nam, David; Mantell, Judith; Achim, Alin; Verkade, Paul

2014-01-01

Correlative light electron microscopy (CLEM) combines the strengths of light and electron microscopy in a single experiment. There are many ways to perform a CLEM experiment and a variety of microscopy modalities can be combined either on separate instruments or as completely integrated solutions. In general, however, a CLEM experiment can be divided into three parts: probes, processing, and analysis. Most of the existing technologies are focussed around the development and use of probes or describe processing methodologies that explain or circumvent some of the compromises that need to be made when performing both light and electron microscopy on the same sample. So far, relatively little attention has been paid to the analysis part of CLEM experiments. Although it is an essential part of each CLEM experiment, it is usually a cumbersome manual process. Here, we briefly discuss each of the three above-mentioned steps, with a focus on the analysis part. We will also introduce an automated registration algorithm that can be applied to the analysis stage to enable the accurate registration of LM and EM images. This facilitates tracing back the right cell/object seen in the light microscope in the EM. © 2014 Elsevier Inc. All rights reserved.

A deletion mutation in the 5' part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins.

PubMed Central

Crawford, S; Goff, S P

1985-01-01

Deletion mutations in the 5' part of the pol gene of Moloney murine leukemia virus were generated by restriction enzyme site-directed mutagenesis of cloned proviral DNA. DNA sequence analysis indicated that one such deletion was localized entirely within the 5' part of the pol gene, did not affect the region encoding reverse transcriptase, and preserved the translational reading frame downstream of the mutation. The major viral precursor polyproteins (Pr65gag, Pr200gag-pol, and gPr80env) were synthesized at wild-type levels in cell lines carrying the mutant genome. These cell lines assembled and released wild-type levels of virion particles into the medium. Cleavage of both Pr65gag and Pr200gag-pol precursors to the mature proteins was completely blocked in the mutant virions. Surprisingly, these virions contained high levels of active reverse transcriptase; examination of the endogenous reverse transcription products synthesized by the mutant virions revealed normal amounts of minus-strand strong-stop DNA, indicating that the RNA genome was packaged and that reverse transcription in detergent-permeabilized virions was not significantly impaired. Processing of gPr80env to gP70env and P15E was not affected by the mutation, but cleavage of P15E to P12E was not observed. The mutant particles were poorly infectious; analysis indicated that infection was blocked at an early stage. The data are consistent with the idea that the 5' part of the pol gene encodes a protease directly responsible for processing Pr65gag, and possibly Pr200gag-pol, to the structural virion proteins. It appears that cleavage of the gag gene product is not required for budding and release of virions and that complete processing of the pol gene product to the mature form of reverse transcriptase is not required for its functional activation. Images PMID:3882995

A Conserved Core of Programmed Cell Death Indicator Genes Discriminates Developmentally and Environmentally Induced Programmed Cell Death in Plants.

PubMed

Olvera-Carrillo, Yadira; Van Bel, Michiel; Van Hautegem, Tom; Fendrych, Matyáš; Huysmans, Marlies; Simaskova, Maria; van Durme, Matthias; Buscaill, Pierre; Rivas, Susana; Coll, Nuria S.; Coppens, Frederik; Maere, Steven; Nowack, Moritz K.

2015-12-01

A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta. © 2015 American Society of Plant Biologists. All Rights Reserved.

Self-Organization Processes at the Intracellular Level

NASA Astrophysics Data System (ADS)

Ponce Dawson, Silvina

2003-03-01

In spite of their relatively small sizes, cells are incredibly complex objects in which various sorts of self-organizing processes occur. Cell division is an example of a process that nearly all cells undergo in which a concerted sequence of events takes place. What are the signals that tell the cell to move along this sequence? Clearly, this is a self-organized process. Microtubules (long polymers that are part of the cytoskeleton) and calcium signals play a major role during cell division. In this course we will focus on some features of microtubule dynamics and calcium signals that are amenable to modeling. In both of these biological systems, behaviors at a single molecule level are key determinants of the self-organized dynamics that is observed at larger scales. Thus, the modeling of these systems presents interesting challenges which require novel strategies. Their study may not only provide answers for biologically motivated questions, but is also a natural setting in which the transition between particle-like and mean-field models can be explored. In this course we will first give a brief biological introduction on the structure of eukaryotic cells, microtubule dynamics and intracellular calcium signals. We will then describe some of the models that have been presented in the literature and discuss the spatio-temporal dynamics that they predict, comparing them with observed behaviors in vitro or in vivo. We will end with a discussion on the virtues and limitations of the various modeling strategies described.

Evaluation of Data Retention Characteristics for Ferroelectric Random Access Memories (FRAMs)

NASA Technical Reports Server (NTRS)

Sharma, Ashok K.; Teverovsky, Alexander

2001-01-01

Data retention and fatigue characteristics of 64 Kb lead zirconate titanate (PZT)-based Ferroelectric Random Access Memories (FRAMs) microcircuits manufactured by Ramtron were examined over temperature range from -85 C to +310 C for ceramic packaged parts and from -85 C to +175 C for plastic parts, during retention periods up to several thousand hours. Intrinsic failures, which were caused by a thermal degradation of the ferroelectric cells, occurred in ceramic parts after tens or hundreds hours of aging at temperatures above 200 C. The activation energy of the retention test failures was 1.05 eV and the extrapolated mean-time-to-failure (MTTF) at room temperature was estimated to be more than 280 years. Multiple write-read cycling (up to 3x10(exp 7)) during the fatigue testing of plastic and ceramic parts did not result in any parametric or functional failures. However, operational currents linearly decreased with the logarithm of number of cycles thus indicating fatigue process in PZT films. Plastic parts, that had more recent date code as compared to ceramic parts, appeared to be using die with improved process technology and showed significantly smaller changes in operational currents and data access times.

Optical diagnostics and computational modeling of reacting and non-reacting single and multiphase flows

NASA Astrophysics Data System (ADS)

Basu, Saptarshi

Three critical problem domains namely water transport in PEM fuel cell, interaction of vortices with diffusion flames and laminar diffusion layers and thermo-physical processes in droplets heated by a plasma or monochromatic radiation have been analyzed in this dissertation. The first part of the dissertation exhibits a unique, in situ, line-of-sight measurements of water vapor partial pressure and temperature in single and multiple gas channels on the cathode side of an operating PEM fuel cell. Tunable diode laser absorption spectroscopy was employed for these measurements for which water transitions sensitive to temperature and partial pressure were utilized. The technique was demonstrated in a PEM fuel cell operating under both steady state and time-varying load conditions. The second part of the dissertation is dedicated to the study of vortex interaction with laminar diffusion flame and non-reacting diffusion layers. For the non-reacting case, a detailed computational study of scalar mixing in a laminar vortex is presented for vortices generated between two gas streams. A detailed parametric study was conducted to determine the effects of vortex strength, convection time, and non-uniform temperature on scalar mixing characteristics. For the reacting case, an experimental study of the interaction of a planar diffusion flame with a line vortex is presented. The flame-vortex interactions are diagnosed by laser induced incandescence for soot yield and by particle image velocimetry for vortex flow characterization. The soot topography was studied as a function of the vortex strength, residence time, flame curvature and the reactant streams from which vortices are initiated. The third part of the dissertation is modeling of thermo-physical processes in liquid ceramic precursor droplets injected into plasma as used in the thermal spray industry to generate thermal barrier coatings on high value materials. Models include aerodynamic droplet break-up process, mixing of droplets in the high temperature plasma, heat and mass transfer within individual droplets as well as droplet precipitation and internal pressurization. The last part of the work is also concerned with the modeling of thermo-physical processes in liquid ceramic precursor droplets heated by monochromatic radiation. Purpose of this work was to evaluate the feasibility of studying precipitation kinetics and morphological changes in a droplet by mimicking similar heating rates as the plasma.

Versican and the regulation of cell phenotype in disease.

PubMed

Wight, Thomas N; Kinsella, Michael G; Evanko, Stephen P; Potter-Perigo, Susan; Merrilees, Mervyn J

2014-08-01

Versican is an extracellular matrix (ECM) proteoglycan that is present in the pericellular environment of most tissues and increases in many different diseases. Versican interacts with cells to influence the ability of cells to proliferate, migrate, adhere and assemble an ECM. The structure of the versican molecule is briefly reviewed and studies highlighting those factors that promote versican synthesis and degradation and their impact on cell phenotype in disease are discussed. Particular attention is given to vascular disease, but other diseases where versican is important are covered as well, most notably different forms of cancers. Attention is given to mechanisms(s) by which versican influences cell behaviors through either direct or indirect processes. Versican produced by either stromal cells or myeloid cells can have a major impact influencing immunity and inflammation. Finally, studies controlling versican accumulation that either delay or inhibit the progression of disease will be highlighted. Versican is one component of the ECM that can influence the ability of cells to proliferate, migrate, adhere, and remodel the ECM. Targeting versican as a way to control cell phenotype offers a novel approach in the treatment of disease. ECM molecules such as versican contribute to the structural integrity of tissues and interact with cells through direct and indirect means to regulate, in part, cellular events that form the basis of disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Reproductive history and breast cancer prevention.

PubMed

Russo, Jose

2016-07-01

The hormonal milieu of an early full-term pregnancy induces lobular development, completing the cycle of differentiation of the breast. This process induces a specific genomic signature in the mammary gland that is represented by the stem cell containing a heterochomatin condensed nucleus (HTN). Even though differentiation significantly reduces cell proliferation in the mammary gland, the mammary epithelium remains capable of responding with proliferation to given stimuli, such as a new pregnancy. The stem cell HTN is able to metabolize the carcinogen and repair the induced DNA damage more efficiently than the stem cell containing an euchromatinic structure (EUN), as it has been demonstrated in the rodent experimental system. The basic biological concept is that pregnancy shifts the stem cell EUN to the stem cell HTN that is refractory to carcinogenesis. Data generated by the use of cDNA micro array techniques have allowed to demonstrate that while lobular development regressed after pregnancy and lactation, programmed cell death genes, DNA repair genes, chromatin remodeling, transcription factors and immune-surveillance gene transcripts all of these genes are upregulated and are part of the genomic signature of pregnancy that is associated with the preventive effect of this physiological process.

[Apoptosis: cellular and clinical aspects].

PubMed

Løvschall, H; Mosekilde, L

1997-04-01

Removal of damaged cells is essential for the maintenance of life in multicellular organisms. The process of self destruction, apoptosis, eliminates surplus or damaged cells as part of the pathophysiological defence system. Apoptosis is essential in structural and functional organogenesis during embryological development. The physiological regulation of tissue kinetics is a product of both cell proliferation and cell death. Internal and external regulatory stimuli regulate the balance between apoptosis and mitosis by genetic interaction. Apoptosis is characterized by condensation of chromatine as a result of DNA degradation, formation of blebs in the plasma and nuclear membranes, condensation of cytoplasma, formation of vesicular apoptotic bodies, and phagocytosis by neighbouring cells without inflammatory response. A number of observations indicate that programmed cell death plays an important role in the regulation of cytofunctional homeostasis and defense against accumulation of damaged cells, eg with DNA alterations. Dysregulation of the apoptotic gene program, eg by mutations, may not only lead to loss or degeneration of tissue, but also to hyperproliferative and tumorigenic disorders. New evidence indicates that apoptosis regulation is important both in aging processes and diseases such as: neuropathies, immunopathies, viral infections, cancer, etc. Pharmacological intervention designed to modulate apoptosis seems to raise new possibilities in the treatment of disease.

Acute mobilization and migration of bone marrow-derived stem cells following anterior cruciate ligament rupture.

PubMed

Maerz, T; Fleischer, M; Newton, M D; Davidson, A; Salisbury, M; Altman, P; Kurdziel, M D; Anderson, K; Bedi, A; Baker, K C

2017-08-01

Little is known regarding acute local and systemic processes following anterior cruciate ligament (ACL) rupture. No study has elucidated whether bone marrow-derived mesenchymal stem cells (MSCs) are mobilized into circulation and recruited to the injured joint. In Part 1, Lewis rats were randomized to noninvasive ACL rupture (Rupture) or non-injured (Control) (n = 6/group). After 72 h, whole blood MSC concentration was assessed using flow cytometry. Synovial fluid and serum were assayed for stromal cell-derived factor (SDF)-1α and cartilage degeneration biomarkers, respectively. In Part 2, 12 additional rats were randomized and intravenously-injected with fluorescently-labeled allogenic MSCs. Cell tracking was performed using longitudinal, in vivo and ex vivo near-infrared (NIR) imaging and histology. Synovium SDF-1α and interleukin (IL)-17A immunostaining was performed. Serum was assayed for SDF-1α and 29 other cytokines. In Part 1, there was a significant increase in MSC concentration and synovial fluid SDF-1α in Rupture. No differences in cartilage biomarkers were observed. In Part 2, Rupture had significantly higher NIR signal at 24, 48, and 72 h, indicating active recruitment of MSCs to the injured joint. Ex vivo cell tracking demonstrated MSC localization in the synovium and myotendinous junction (MTJ) of the quadriceps. Injured synovia exhibited increased synovitis grade and higher degree of IL-17A and SDF-1α immunostaining. ACL rupture induced peripheral blood mobilization of MSCs and migration of intravenously-injected allogenic MSCs to the injured joint, where they localized in the synovium and quadriceps MTJ. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Extended Self-Renewal and Accelerated Reprogramming in the Absence of Kdm5b

PubMed Central

Hu, Gangqing; Yu, Zu-Xi; Liu, Chengyu

2013-01-01

Embryonic stem (ES) cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in induced pluripotent stem (iPS) cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with the epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process. PMID:24100015

MicroRNA profiling of antler stem cells in potentiated and dormant states and their potential roles in antler regeneration.

PubMed

Ba, Hengxing; Wang, Datao; Li, Chunyi

2016-04-01

MicroRNAs (miRNAs) can effectively regulate gene expression at the post-transcriptional level and play a critical role in tissue growth, development and regeneration. Our previous studies showed that antler regeneration is a stem cell-based process and antler stem cells reside in the periosteum of a pedicle, the permanent bony protuberance, from which antler regeneration takes place. Antlers are the only mammalian organ that can fully regenerate and hence provide a unique opportunity to identify miRNAs that are involved in organ regeneration. In the present study, we used next generation sequencing technology sequenced miRNAs of the stem cells derived from either the potentiated or the dormant pedicle periosteum. A population of both conserved and 20 deer-specific miRNAs was identified. These conserved miRNAs were derived from 453 homologous hairpin precursors across 88 animal species, and were further grouped into 167 miRNA families. Among them, the miR-296 is embryonic stem cell-specific. The potentiation process resulted in the significant regulation (>±2 Fold, q value <0.05) of conserved miRNAs; 8 miRNA transcripts were down- and 6 up-regulated. Several GO biology processes and the Wnt, MAPK and TGF-beta signaling pathways were found to be up-regulated as part of antlerogenic stem cell potentiation process. This research has identified miRNAs that are associated either with the dormant or the potentiated antler stem cells and identified some target miRNAs for further research into their role played in mammalian organ regeneration.

The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

PubMed Central

Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

2018-01-01

The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

[Oxidative stress and infectious pathology].

PubMed

Romero Alvira, D; Guerrero Navarro, L; Gotor Lázaro, M A; Roche Collado, E

1995-03-01

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.

Microwave-Assisted Extraction for Microalgae: From Biofuels to Biorefinery

PubMed Central

Pandhal, Jagroop

2018-01-01

The commercial reality of bioactive compounds and oil production from microalgal species is constrained by the high cost of production. Downstream processing, which includes harvesting and extraction, can account for 70–80% of the total cost of production. Consequently, from an economic perspective extraction technologies need to be improved. Microalgal cells are difficult to disrupt due to polymers within their cell wall such as algaenan and sporopollenin. Consequently, solvents and disruption devices are required to obtain products of interest from within the cells. Conventional techniques used for cell disruption and extraction are expensive and are often hindered by low efficiencies. Microwave-assisted extraction offers a possibility for extraction of biochemical components including lipids, pigments, carbohydrates, vitamins and proteins, individually and as part of a biorefinery. Microwave technology has advanced since its use in the 1970s. It can cut down working times and result in higher yields and purity of products. In this review, the ability and challenges in using microwave technology are discussed for the extraction of bioactive products individually and as part of a biorefinery approach. PMID:29462888

Fluid models and simulations of biological cell phenomena

NASA Technical Reports Server (NTRS)

Greenspan, H. P.

1982-01-01

The dynamics of coated droplets are examined within the context of biofluids. Of specific interest is the manner in which the shape of a droplet, the motion within it as well as that of aggregates of droplets can be controlled by the modulation of surface properties and the extent to which such fluid phenomena are an intrinsic part of cellular processes. From the standpoint of biology, an objective is to elucidate some of the general dynamical features that affect the disposition of an entire cell, cell colonies and tissues. Conventionally averaged field variables of continuum mechanics are used to describe the overall global effects which result from the myriad of small scale molecular interactions. An attempt is made to establish cause and effect relationships from correct dynamical laws of motion rather than by what may have been unnecessary invocation of metabolic or life processes. Several topics are discussed where there are strong analogies droplets and cells including: encapsulated droplets/cell membranes; droplet shape/cell shape; adhesion and spread of a droplet/cell motility and adhesion; and oams and multiphase flows/cell aggregates and tissues. Evidence is presented to show that certain concepts of continuum theory such as suface tension, surface free energy, contact angle, bending moments, etc. are relevant and applicable to the study of cell biology.

Processing of two latent membrane protein 1 MHC class I epitopes requires tripeptidyl peptidase II involvement.

PubMed

Diekmann, Jan; Adamopoulou, Eleni; Beck, Olaf; Rauser, Georg; Lurati, Sarah; Tenzer, Stefan; Einsele, Hermann; Rammensee, Hans-Georg; Schild, Hansjörg; Topp, Max S

2009-08-01

The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential target for T cell immunotherapy in EBV-related malignancies. However, only a few CD8(+) T cell epitopes are known, and the benefit of LMP1-specific T cell immunotherapy has not yet been proven. In this work, we studied the processing of the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL. We found that target cells endogenously expressing the native LMP1 are not recognized by CTLs specific for these epitopes because the N-terminal part of LMP1 limits the efficiency of epitope generation. We further observed that the proteasome is not required for the generation of both epitopes and that the YLLEMLRWL epitope seems to be destroyed by the proteasome, because blocking of proteasomal activities enhanced specific CTL activation. Activation of LMP1-specific CTLs could be significantly reduced after inhibition of the tripeptidyl peptidase II, suggesting a role for this peptidase in the processing of both epitopes. Taken together, our results demonstrate that the MHC class I-restricted LMP1 epitopes studied in this work are two of very few epitopes known to date to be processed proteasome independently by tripeptidyl peptidase II.

Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome

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

Kitagawa, Yukiko; Department of Oral and Maxillofacial Surgery II, Osaka University, Osaka 565-0871; Kameoka, Masanori

2008-03-30

The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2{alpha}) was revealed to significantly up-regulate the replication of human immunodeficiency virus type 1 (HIV-1). This effect was confirmed by cell infection with vesicular stomatitis virus G protein-pseudotyped HIV-1 as well as CXCR4-tropic and CCR5-tropic HIV-1. Viral adsorption, viral entry and reverse transcription processes were not affected by cell transfection with siRNA against AP2{alpha}. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2{alpha}. Confocal fluorescence microscopy revealed that a subpopulation of AP2{alpha} wasmore » not only localized in the cytoplasm but was also partly co-localized with lamin B, importin {beta} and Nup153, implying that AP2{alpha} negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2{alpha} may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle.« less

The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

PubMed

Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

2014-06-01

To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process. © 2013 Japanese Society of Neuropathology.

Aging yeast gain a competitive advantage on non-optimal carbon sources.

PubMed

Frenk, Stephen; Pizza, Grazia; Walker, Rachael V; Houseley, Jonathan

2017-06-01

Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Analysis on flexible manufacturing system layout using arena simulation software

NASA Astrophysics Data System (ADS)

Fadzly, M. K.; Saad, Mohd Sazli; Shayfull, Z.

2017-09-01

Flexible manufacturing system (FMS) was defined as highly automated group technology machine cell, consisting of a group of processing stations interconnected by an automated material handling and storage system, and controlled by an integrated computer system. FMS can produce parts or products are in the mid-volume, mid-variety production range. The layout system in FMS is an important criterion to design the FMS system to produce a part or product. This facility layout of an FMS involves the positioning of cells within given boundaries, so as to minimize the total projected travel time between cells. Defining the layout includes specifying the spatial coordinates of each cell, its orientation in either a horizontal or vertical position, and the location of its load or unloads point. There are many types of FMS layout such as In-line, loop ladder and robot centered cell layout. The research is concentrating on the design and optimization FMS layout. The final conclusion can be summarized that the objective to design and optimisation of FMS layout for this study is successful because the FMS In-line layout is the best layout based on effective time and cost using ARENA simulation software.

Functional role of inorganic trace elements in angiogenesis part III: (Ti, Li, Ce, As, Hg, Va, Nb and Pb).

PubMed

Saghiri, Mohammad Ali; Orangi, Jafar; Asatourian, Armen; Sorenson, Christine M; Sheibani, Nader

2016-02-01

Many essential elements exist in nature with significant influence on human health. Angiogenesis is vital in developmental, repair, and regenerative processes, and its aberrant regulation contributes to pathogenesis of many diseases including cancer. Thus, it is of great importance to explore the role of these elements in such a vital process. This is third in a series of reviews that serve as an overview of the role of inorganic elements in regulation of angiogenesis and vascular function. Here we will review the roles of titanium, lithium, cerium, arsenic, mercury, vanadium, niobium, and lead in these processes. The roles of other inorganic elements in angiogenesis were discussed in part I (N, Fe, Se, P, Au, and Ca) and part II (Cr, Si, Zn, Cu, and S) of these series. The methods of exposure, structure, mechanisms, and potential activities of these elements are briefly discussed. An electronic search was performed on the role of these elements in angiogenesis from January 2005 to April 2014. These elements can promote and/or inhibit angiogenesis through different mechanisms. The anti-angiogenic effect of titanium dioxide nanoparticles comes from the inhibition of angiogenic processes, and not from its toxicity. Lithium affects vasculogenesis but not angiogenesis. Nanoceria treatment inhibited tumor growth by inhibiting angiogenesis. Vanadium treatment inhibited cell proliferation and induced cytotoxic effects through interactions with DNA. The negative impact of mercury on endothelial cell migration and tube formation activities was dose and time dependent. Lead induced IL-8 production, which is known to promote tumor angiogenesis. Thus, understanding the impact of these elements on angiogenesis will help in development of new modalities to modulate angiogenesis under various conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Innovation: an emerging focus from cells to societies.

PubMed

Hochberg, Michael E; Marquet, Pablo A; Boyd, Robert; Wagner, Andreas

2017-12-05

Innovations are generally unexpected, often spectacular changes in phenotypes and ecological functions. The contributions to this theme issue are the latest conceptual, theoretical and experimental developments, addressing how ecology, environment, ontogeny and evolution are central to understanding the complexity of the processes underlying innovations. Here, we set the stage by introducing and defining key terms relating to innovation and discuss their relevance to biological, cultural and technological change. Discovering how the generation and transmission of novel biological information, environmental interactions and selective evolutionary processes contribute to innovation as an ecosystem will shed light on how the dominant features across life come to be, generalize to social, cultural and technological evolution, and have applications in the health sciences and sustainability.This article is part of the theme issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

Innovation: an emerging focus from cells to societies

PubMed Central

Boyd, Robert

2017-01-01

Innovations are generally unexpected, often spectacular changes in phenotypes and ecological functions. The contributions to this theme issue are the latest conceptual, theoretical and experimental developments, addressing how ecology, environment, ontogeny and evolution are central to understanding the complexity of the processes underlying innovations. Here, we set the stage by introducing and defining key terms relating to innovation and discuss their relevance to biological, cultural and technological change. Discovering how the generation and transmission of novel biological information, environmental interactions and selective evolutionary processes contribute to innovation as an ecosystem will shed light on how the dominant features across life come to be, generalize to social, cultural and technological evolution, and have applications in the health sciences and sustainability. This article is part of the theme issue ‘Process and pattern in innovations from cells to societies’. PMID:29061887

First Demonstration on Direct Laser Fabrication of Lunar Regolith Parts

NASA Technical Reports Server (NTRS)

Balla, Vamsi Krishna; Roberson, Luke B.; OConnor, Gregory W. O.; Trigwell, Stephen; Bose, Susmita; Bandyopadhyay, Amit

2010-01-01

Establishment of a lunar or Martian outpost necessitates the development of methods to utilize in situ mineral resources for various construction and resource extraction applications. Fabrication technologies are critical for habitat structure development, as well as repair and replacement of tools and parts at the outpost. Herein we report the direct fabrication of lunar regolith simulant parts, in freeform environment, using lasers. We show that raw lunar regolith can be processed at laser energy levels as a low as 2.12 J mm-2 resulting in nanocrystalline and/or amorphous microstructures. Potential applications of laser based fabrication technologies to make useful regolith parts for various applications including load bearing composite structures, radiation shielding, and solar cell substrates is described.

Infrared and Raman Microscopy in Cell Biology

PubMed Central

Matthäus, Christian; Bird, Benjamin; Miljković, Miloš; Chernenko, Tatyana; Romeo, Melissa; Diem, Max

2009-01-01

This chapter presents novel microscopic methods to monitor cell biological processes of live or fixed cells without the use of any dye, stains, or other contrast agent. These methods are based on spectral techniques that detect inherent spectroscopic properties of biochemical constituents of cells, or parts thereof. Two different modalities have been developed for this task. One of them is infrared micro-spectroscopy, in which an average snapshot of a cell’s biochemical composition is collected at a spatial resolution of typically 25 mm. This technique, which is extremely sensitive and can collect such a snapshot in fractions of a second, is particularly suited for studying gross biochemical changes. The other technique, Raman microscopy (also known as Raman micro-spectroscopy), is ideally suited to study variations of cellular composition on the scale of subcellular organelles, since its spatial resolution is as good as that of fluorescence microscopy. Both techniques exhibit the fingerprint sensitivity of vibrational spectroscopy toward biochemical composition, and can be used to follow a variety of cellular processes. PMID:19118679

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

PubMed

Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

A neural model of motion processing and visual navigation by cortical area MST.

PubMed

Grossberg, S; Mingolla, E; Pack, C

1999-12-01

Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.

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

Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.

We report that exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstratemore » that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, we determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.« less

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.

Squamous epithelium formation in the respiratory intestine of the bronze Corydoras Corydoras aeneus (Callichthyidae Teleostei).

PubMed

Satora, Leszek; Kozioł, Katarzyna; Zebrowski, Jacek

2017-06-01

Accessory respiratory organs in fish exhibit great diversity but share the presence of numerous capillaries covered by a simple squamous epithelium. The adoption of the intestine for respiratory function needs certain special modifications. In this study, we explored immunohistochemical and metabolic fingerprint features that could underlay this adaptation in bronze corydoras Corydoras aeneus. Immunohistochemical localization of the cytoplasmic domain of epidermal growth factor receptor (EGFR) in the respiratory part of intestine demonstrated a strong positive immunoreaction in epithelial cells and connective tissue. Fourier Transfer Infrared (FTIR) spectroscopy coupled with chemometrics discriminated between anterior and posterior region of intestine in terms of secondary structure of proteins and the abundance of p-cresol and other phenolics. The latter were reduced in the posterior part of intestine, indicating the cessation of digestive function in this region. It has been suggested that aquatic hypoxia via endocrine cells (hypoxia-sensitive) activate EGFR, which induce proliferation of squamous epithelial cells, thereby enabling gas diffusion in the posterior part of intestine. It seems that hypoxia and normoxia are opposed conditions adjusting the production of squamous epithelial cells in this intestine. The physiological role of EGFR in the respiratory intestine of bronze corydoras is of interest not only from an evolutionary aspect but also in terms of a potential model for observations process proliferation squamous epithelial cells. Future investigations on the molecular responses to different water oxygen levels in air-breathing bronze corydoras fish are required to clarify the mechanism responsible for squamous cell proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Silk fibroin scaffolds with inverse opal structure for bone tissue engineering.

PubMed

Sommer, Marianne R; Vetsch, Jolanda R; Leemann, Jessica; Müller, Ralph; Studart, André R; Hofmann, Sandra

2017-10-01

How scaffold porosity, pore diameter and geometry influence cellular behavior is-although heavily researched - merely understood, especially in 3D. This is mainly caused by a lack of suitable, reproducible scaffold fabrication methods, with processes such as gas foaming, lyophilization or particulate leaching still being the standard. Here we propose a method to generate highly porous silk fibroin scaffolds with monodisperse spherical pores, namely inverse opals, and study their effect on cell behavior. These silk fibroin inverse opal scaffolds were compared to salt-leached silk fibroin scaffolds in terms of human mesenchymal stem cell response upon osteogenic differentiation signals. While cell number remained similar on both scaffold types, extracellular matrix mineralization nearly doubled on the newly developed scaffolds, suggesting a positive effect on cell differentiation. By using the very same material with comparable average pore diameters, this increase in mineral content can be attributed to either the differences in pore diameter distribution or the pore geometry. Although the exact mechanisms leading to enhanced mineralization in inverse opals are not yet fully understood, our results indicate that control over pore geometry alone can have a major impact on the bioactivity of a scaffold toward stem cell differentiation into bone tissue. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2074-2084, 2017. © 2016 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

Synchronized mammalian cell culture: part I--a physical strategy for synchronized cultivation under physiological conditions.

PubMed

Barradas, Oscar Platas; Jandt, Uwe; Becker, Max; Bahnemann, Janina; Pörtner, Ralf; Zeng, An-Ping

2015-01-01

Conventional analysis and optimization procedures of mammalian cell culture processes mostly treat the culture as a homogeneous population. Hence, the focus is on cell physiology and metabolism, cell line development, and process control strategy. Impact on cultivations caused by potential variations in cellular properties between different subpopulations, however, has not yet been evaluated systematically. One main cause for the formation of such subpopulations is the progress of all cells through the cell cycle. The interaction of potential cell cycle specific variations in the cell behavior with large-scale process conditions can be optimally determined by means of (partially) synchronized cultivations, with subsequent population resolved model analysis. Therefore, it is desirable to synchronize a culture with minimal perturbation, which is possible with different yield and quality using physical selection methods, but not with frequently used chemical or whole-culture methods. Conventional nonsynchronizing methods with subsequent cell-specific, for example, flow cytometric analysis, can only resolve cell-limited effects of the cell cycle. In this work, we demonstrate countercurrent-flow centrifugal elutriation as a useful physical method to enrich mammalian cell populations within different phases of a cell cycle, which can be further cultivated for synchronized growth in bioreactors under physiological conditions. The presented combined approach contrasts with other physical selection methods especially with respect to the achievable yield, which makes it suitable for bioreactor scale cultivations. As shown with two industrial cell lines (CHO-K1 and human AGE1.HN), synchronous inocula can be obtained with overall synchrony degrees of up to 82% in the G1 phase, 53% in the S phase and 60% in the G2/M phase, with enrichment factors (Ysync) of 1.71, 1.79, and 4.24 respectively. Cells are able to grow with synchrony in bioreactors over several cell cycles. This strategy, combined with population-resolved model analysis and parameter extraction as described in the accompanying paper, offers new possibilities for studies of cell lines and processes at levels of cell cycle and population under physiological conditions. © 2014 American Institute of Chemical Engineers.

Integral bypass diodes in an amorphous silicon alloy photovoltaic module

NASA Technical Reports Server (NTRS)

Hanak, J. J.; Flaisher, H.

1991-01-01

Thin-film, tandem-junction, amorphous silicon (a-Si) photovoltaic modules were constructed in which a part of the a-Si alloy cell material is used to form bypass protection diodes. This integral design circumvents the need for incorporating external, conventional diodes, thus simplifying the manufacturing process and reducing module weight.

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes

PubMed Central

Dosekova, Erika; Filip, Jaroslav; Bertok, Tomas; Both, Peter; Kasak, Peter; Tkac, Jan

2017-01-01

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well. PMID:27859448

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes.

PubMed

Dosekova, Erika; Filip, Jaroslav; Bertok, Tomas; Both, Peter; Kasak, Peter; Tkac, Jan

2017-05-01

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well. © 2016 Wiley Periodicals, Inc.

[A comparative analysis of notochord formation in amphibian embryos].

PubMed

Novoselov, V V

1992-01-01

We studied the origin, structure, and development of the notochord in Pleurodeles waltlii (Urodela) and Xenopus laevis (Anura) embryos. The notochord rudiment is formed in both species at the early gastrula stage as a cluster of polarized chorda-mesoderm cells located along the sagittal plane of the embryo. In Pl. waltlii the notochord rudiment is separated from the gastrocoele roof as a result of contraction of apical cell surfaces. The contraction wave spreads forward and backward along craniocaudal axis, i.e., segregation of the notochord rudiment progresses in two directions simultaneously. Similar process takes place in X. laevis embryos; however, propagation of the contraction wave in the anterior part of the body somewhat differs from that in the posterior part. While the "anterior" contraction wave resembles that in Pl. waltlii embryos, progression of the wave in the posterior part of the body is distinguished by a closer association of the notochord rudiment with ectoderm and the presence of its delamination boundaries with the somite mesoderm.

Differentiation of chondrocytes and scleroblasts during dorsal fin skeletogenesis in flounder larvae.

PubMed

Suzuki, Tohru; Haga, Yutaka; Takeuchi, Toshio; Uji, Susumu; Hashimoto, Hisashi; Kurokawa, Tadahide

2003-01-01

In teleosts, the embryonic fin fold consists of a peridermis, an underlying epidermis and a small number of mesenchymal cells. Beginning from such a simple structure, the fin skeletons, including the proximal and distal radials and lepidotrichia (finrays), develop in the dorsal fin fold at the larval stage. Their process of skeletogenesis and embryonic origin are unclear. Using flounder larvae, we report the differentiation process for chondrocytes and scleroblasts prior to fin skeletogenesis and the effects of retinoic acid (RA) on it. In early larvae, the mesenchymal cells grow between the epidermis and spinal cord to form a line of periodical condensations, which are proximal radial primordia, to produce chondrocytes. The prescleroblasts, which ossify the proximal radial cartilages, differentiate in the mesenchymal cells remaining between the cartilages. Then, mesenchymal condensations occur between the distal ends of the proximal radials, forming distal radial primordia, to produce chondrocytes. Simultaneously, condensations occur between the distal radial primordia and peridermis, which are lepidotrichia primordia, to produce prescleroblasts. Exogenous RA specifically inhibits the mesenchymal condensation prior to the proximal radial formation together with the down-regulation of sonic hedgehog (shh) and patched (pta) expression, resulting in the loss of proximal radials. Thus, it was indicated that differentiation of the precursor cells of radials and lepidotrichia begins in the proximal part of the fin fold and that the initial mesenchymal condensation prior to the proximal radial formation is highly susceptible to the effects of RA. Lepidotrichia formation does not occur where proximal radials are absent, indicating that lepidotrichia differentiation requires interaction with the radial cartilages. To examine the suggestion that neural crest cells contribute to the medial fin skeletons, we localized the HNK-1 positive cells in flounder embryos and slug and msxb-positive cells in pufferfish, Fugu rubripes, embryos. That the positive cells commonly arrive at the proximal part of the fin fold does not contradict the suggestion, but their final destiny as radial chondrocytes or lepidotrichia scleroblasts, should be further investigated.

Test Result of 650 MHz, Beta 0.61 Single Cell Niobium Cavity

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

Seth, Sudeshna; Bhattacharyya, Pranab; Dutta Gupta, Anjan

VECC has been involved in the design, analysis and development of 650 MHz, beta 0.61 (LB650), elliptical Superconducting RF linac cavity, as part of research and development activities on SRF cavities and associated technologies under Indian Institutions Fermilab Collaboration (IIFC). A single-cell niobium cavity has been indigenously designed and developed at VECC, with the help of Electron Beam Welding (EBW) facility at IUAC, New Delhi. Various measurements, processing and testing at 2K in Vertical Test Stand (VTS) of the single-cell cavity was carried out at ANL and Fermilab, USA, with active participation of VECC engineers. It achieved a maximum acceleratingmore » gradient(Eacc) of 34.5 MV/m with Quality Factor of 2·10⁹ and 30 MV/m with Quality Factor of 1.5·10¹⁰. This is probably the highest accelerating gradient achieved so far in the world for LB650 cavities. This paper describes the design, fabrication and measurement of the single cell niobium cavity. Cavity processing and test results of Vertical Test of the single-cell niobium cavity are also presented.« less

Review of the Potential of the Ni/Cu Plating Technique for Crystalline Silicon Solar Cells

PubMed Central

Rehman, Atteq ur; Lee, Soo Hong

2014-01-01

Developing a better method for the metallization of silicon solar cells is integral part of realizing superior efficiency. Currently, contact realization using screen printing is the leading technology in the silicon based photovoltaic industry, as it is simple and fast. However, the problem with metallization of this kind is that it has a lower aspect ratio and higher contact resistance, which limits solar cell efficiency. The mounting cost of silver pastes and decreasing silicon wafer thicknesses encourages silicon solar cell manufacturers to develop fresh metallization techniques involving a lower quantity of silver usage and not relying pressing process of screen printing. In recent times nickel/copper (Ni/Cu) based metal plating has emerged as a metallization method that may solve these issues. This paper offers a detailed review and understanding of a Ni/Cu based plating technique for silicon solar cells. The formation of a Ni seed layer by adopting various deposition techniques and a Cu conducting layer using a light induced plating (LIP) process are appraised. Unlike screen-printed metallization, a step involving patterning is crucial for opening the masking layer. Consequently, experimental procedures involving patterning methods are also explicated. Lastly, the issues of adhesion, back ground plating, process complexity and reliability for industrial applications are also addressed. PMID:28788516

Review of the Potential of the Ni/Cu Plating Technique for Crystalline Silicon Solar Cells.

PubMed

Rehman, Atteq Ur; Lee, Soo Hong

2014-02-18

Developing a better method for the metallization of silicon solar cells is integral part of realizing superior efficiency. Currently, contact realization using screen printing is the leading technology in the silicon based photovoltaic industry, as it is simple and fast. However, the problem with metallization of this kind is that it has a lower aspect ratio and higher contact resistance, which limits solar cell efficiency. The mounting cost of silver pastes and decreasing silicon wafer thicknesses encourages silicon solar cell manufacturers to develop fresh metallization techniques involving a lower quantity of silver usage and not relying pressing process of screen printing. In recent times nickel/copper (Ni/Cu) based metal plating has emerged as a metallization method that may solve these issues. This paper offers a detailed review and understanding of a Ni/Cu based plating technique for silicon solar cells. The formation of a Ni seed layer by adopting various deposition techniques and a Cu conducting layer using a light induced plating (LIP) process are appraised. Unlike screen-printed metallization, a step involving patterning is crucial for opening the masking layer. Consequently, experimental procedures involving patterning methods are also explicated. Lastly, the issues of adhesion, back ground plating, process complexity and reliability for industrial applications are also addressed.

Very High Density of Chinese Hamster Ovary Cells in Perfusion by Alternating Tangential Flow or Tangential Flow Filtration in WAVE Bioreactor™—Part II: Applications for Antibody Production and Cryopreservation

PubMed Central

Clincke, Marie-Françoise; Mölleryd, Carin; Samani, Puneeth K; Lindskog, Eva; Fäldt, Eric; Walsh, Kieron; Chotteau, Véronique

2013-01-01

A high cell density perfusion process of monoclonal antibody (MAb) producing Chinese hamster ovary (CHO) cells was developed in disposable WAVE Bioreactor™ using external hollow fiber (HF) filter as cell separation device. Tangential flow filtration (TFF) and alternating tangential flow (ATF) systems were compared and process applications of high cell density perfusion were studied here: MAb production and cryopreservation. Operations by perfusion using microfiltration (MF) or ultrafiltration (UF) with ATF or TFF and by fed-batch were compared. Cell densities higher than 108 cells/mL were obtained using UF TFF or UF ATF. The cells produced comparable amounts of MAb in perfusion by ATF or TFF, MF or UF. MAbs were partially retained by the MF using ATF or TFF but more severely using TFF. Consequently, MAbs were lost when cell broth was discarded from the bioreactor in the daily bleeds. The MAb cell-specific productivity was comparable at cell densities up to 1.3 × 108 cells/mL in perfusion and was comparable or lower in fed-batch. After 12 days, six times more MAbs were harvested using perfusion by ATF or TFF with MF or UF, compared to fed-batch and 28× more in a 1-month perfusion at 108 cells/mL density. Pumping at a recirculation rate up to 2.75 L/min did not damage the cells with the present TFF settings with HF short circuited. Cell cryopreservation at 0.5 × 108 and 108 cells/mL was performed using cells from a perfusion run at 108 cells/mL density. Cell resuscitation was very successful, showing that this system was a reliable process for cell bank manufacturing. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:768–777, 2013 PMID:23436783

Flat-plate solar array project. Volume 5: Process development

NASA Technical Reports Server (NTRS)

Gallagher, B.; Alexander, P.; Burger, D.

1986-01-01

The goal of the Process Development Area, as part of the Flat-Plate Solar Array (FSA) Project, was to develop and demonstrate solar cell fabrication and module assembly process technologies required to meet the cost, lifetime, production capacity, and performance goals of the FSA Project. R&D efforts expended by Government, Industry, and Universities in developing processes capable of meeting the projects goals during volume production conditions are summarized. The cost goals allocated for processing were demonstrated by small volume quantities that were extrapolated by cost analysis to large volume production. To provide proper focus and coverage of the process development effort, four separate technology sections are discussed: surface preparation, junction formation, metallization, and module assembly.

KSC-2012-3109

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – A technician controls a special crane as it lifts a newly removed fuel cell from space shuttle Endeavour's payload bay. The operation took place inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3103

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida, technicians use a special crane to lift a fuel cell out of space shuttle Endeavour's payload bay. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3105

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Technicians monitor the progress as one of space shuttle Endeavour's three fuel cells is removed from the vehicle's payload bay. The operation took place inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

The Cellular Autophagy Pathway Modulates Human T-Cell Leukemia Virus Type 1 Replication

PubMed Central

Tang, Sai-Wen; Chen, Chia-Yen; Klase, Zachary; Zane, Linda

2013-01-01

Autophagy, a general homeostatic process for degradation of cytosolic proteins or organelles, has been reported to modulate the replication of many viruses. The role of autophagy in human T-cell leukemia virus type 1 (HTLV-1) replication has, however, been uncharacterized. Here, we report that HTLV-1 infection increases the accumulation of autophagosomes and that this accumulation increases HTLV-1 production. We found that the HTLV-1 Tax protein increases cellular autophagosome accumulation by acting to block the fusion of autophagosomes to lysosomes, preventing the degradation of the former by the latter. Interestingly, the inhibition of cellular autophagosome-lysosome fusion using bafilomycin A increased the stability of the Tax protein, suggesting that cellular degradation of Tax occurs in part through autophagy. Our current findings indicate that by interrupting the cell's autophagic process, Tax exerts a positive feedback on its own stability. PMID:23175371

KSC-2012-3110

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Technicians inside Kennedy Space Center's Orbiter Processing Facility-2 lower one of space shuttle Endeavour's recently removed fuel cells onto a waiting platform. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3108

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida, a crane hoists one of space shuttle Endeavour's three fuel cells out of the vehicle's payload bay. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3107

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Technicians inside Kennedy Space Center's Orbiter Processing Facility-2 lower one of space shuttle Endeavour's recently removed fuel cells onto a waiting platform. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3106

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida, a technician guides a newly removed fuel cell up and out of space shuttle Endeavour's payload bay. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

KSC-2012-3104

NASA Image and Video Library

2012-05-29

CAPE CANAVERAL, Fla. – Inside Orbiter Processing Facility-2 at NASA's Kennedy Space Center in Florida, technicians use a special crane to lift a fuel cell out of space shuttle Endeavour's payload bay. All three of Endeavour's fuel cells were removed and will be drained of fluids. The hydrogen and oxygen dewars which feed reactants to the fuel cells remain in Endeavour's midbody and will be purged with inert gases and vented down. The work is part of the Space Shuttle Program's transition and retirement processing of shuttle Endeavour, which is being prepared for public display at the California Science Center in Los Angeles. Its ferry flight to California is targeted for mid-September. Endeavour was the last space shuttle added to NASA's orbiter fleet. Over the course of its 19-year career, Endeavour spent 299 days in space during 25 missions. For more information, visit http://www.nasa.gov/shuttle. Photo credit: NASA/Glenn Benson

Regulation of axonal development by the nuclear protein hindsight (pebbled) in the Drosophila visual system.

PubMed

Oliva, Carlos; Sierralta, Jimena

2010-08-15

The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. Copyright 2010 Elsevier Inc. All rights reserved.

The Hypoxic Testicle: Physiology and Pathophysiology

PubMed Central

Reyes, Juan G.; Farias, Jorge G.; Henríquez-Olavarrieta, Sebastián; Madrid, Eva; Parraga, Mario; Zepeda, Andrea B.; Moreno, Ricardo D.

2012-01-01

Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia. PMID:23056665

Efficient Isolation Protocol for B and T Lymphocytes from Human Palatine Tonsils

PubMed Central

Assadian, Farzaneh; Sandström, Karl; Laurell, Göran; Svensson, Catharina; Akusjärvi, Göran; Punga, Tanel

2015-01-01

Tonsils form a part of the immune system providing the first line of defense against inhaled pathogens. Usually the term “tonsils” refers to the palatine tonsils situated at the lateral walls of the oral part of the pharynx. Surgically removed palatine tonsils provide a convenient accessible source of B and T lymphocytes to study the interplay between foreign pathogens and the host immune system. This video protocol describes the dissection and processing of surgically removed human palatine tonsils, followed by the isolation of the individual B and T cell populations from the same tissue sample. We present a method, which efficiently separates tonsillar B and T lymphocytes using an antibody-dependent affinity protocol. Further, we use the method to demonstrate that human adenovirus infects specifically the tonsillar T cell fraction. The established protocol is generally applicable to efficiently and rapidly isolate tonsillar B and T cell populations to study the role of different types of pathogens in tonsillar immune responses. PMID:26650582

Autologous osteoblast transplantation, an innovative method of bone defect treatment: role of a tissue and cell bank in the process.

PubMed

Olender, E; Brubaker, S; Uhrynowska-Tyszkiewicz, I; Wojtowicz, A; Kaminski, A

2014-10-01

The idea of cell treatment of various diseases and medical conditions has become very popular. Some procedures are well established, as is autologous chondrocyte implantation, whereas others are still in the process of early development, laboratory experiments, and some clinical trials. This report is devoted to an example of an emerging cell treatment: bone augmentation with the use of autologous cells and its legal and technical background. Various requirements set by law must be met by tissue banks performing cell seeding of grafts. In Europe, the requirements are described in directives 2004/23/EC, 2006/17/EC, 2006/86/EC, and in the regulation 2007/1394/EC. Revitalization of biostatic allografts gives new, promising tools for creation of functional parts of organs; brings the methodology used in tissue banks closer to tissue engineering; places the enterprise in the mainstream of advanced biotechnology; allows the full potential of tissue allografts; and opens a new, large area for clinical and laboratory research. Cell and tissue processing also have a financial impact on the treatment: it produces additional expenditures. Clinical effectiveness will be the most decisive factor of whether this innovative treatment will be applied in a particular type of medical condition. From a tissue establishment perspective, the most important issue is to develop a procedure that ensures safety for the patient in graft quality terms.

Back-junction back-contact n-type silicon solar cell with diffused boron emitter locally blocked by implanted phosphorus

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

Müller, Ralph, E-mail: ralph.mueller@ise.fraunhofer.de; Schrof, Julian; Reichel, Christian

2014-09-08

The highest energy conversion efficiencies in the field of silicon-based photovoltaics have been achieved with back-junction back-contact (BJBC) silicon solar cells by several companies and research groups. One of the most complex parts of this cell structure is the fabrication of the locally doped p- and n-type regions, both on the back side of the solar cell. In this work, we introduce a process sequence based on a synergistic use of ion implantation and furnace diffusion. This sequence enables the formation of all doped regions for a BJBC silicon solar cell in only three processing steps. We observed that implantedmore » phosphorus can block the diffusion of boron atoms into the silicon substrate by nearly three orders of magnitude. Thus, locally implanted phosphorus can be used as an in-situ mask for a subsequent boron diffusion which simultaneously anneals the implanted phosphorus and forms the boron emitter. BJBC silicon solar cells produced with such an easy-to-fabricate process achieved conversion efficiencies of up to 21.7%. An open-circuit voltage of 674 mV and a fill factor of 80.6% prove that there is no significant recombination at the sharp transition between the highly doped emitter and the highly doped back surface field at the device level.« less

Biopolymer foams - Relationship between material characteristics and foaming behavior of cellulose based foams

NASA Astrophysics Data System (ADS)

Rapp, F.; Schneider, A.; Elsner, P.

2014-05-01

Biopolymers are becoming increasingly important to both industry and consumers. With regard to waste management, CO2 balance and the conservation of petrochemical resources, increasing efforts are being made to replace standard plastics with bio-based polymers. Nowadays biopolymers can be built for example of cellulose, lactic acid, starch, lignin or bio mass. The paper will present material properties of selected cellulose based polymers (cellulose propionate [CP], cellulose acetate butyrate [CAB]) and corresponding processing conditions for particle foams as well as characterization of produced parts. Special focus is given to the raw material properties by analyzing thermal behavior (differential scanning calorimetry), melt strength (Rheotens test) and molecular weight distribution (gel-permeation chromatography). These results will be correlated with the foaming behavior in a continuous extrusion process with physical blowing agents and underwater pelletizer. Process set-up regarding particle foam technology, including extrusion foaming and pre-foaming, will be shown. The characteristics of the resulting foam beads will be analyzed regarding part density, cell morphology and geometry. The molded parts will be tested on thermal conductivity as well as compression behavior (E-modulus, compression strength).

Inclusions, Porosity, and Fatigue of AlSi10Mg Parts Produced by Selective Laser Melting

NASA Astrophysics Data System (ADS)

Tang, Ming

Additive manufacturing (AM) has experienced remarkable growth in the past decade with applications in both rapid prototyping and rapid manufacturing for functional end-usable parts. As one of the most promising AM processes, selective laser melting (SLM) can be used to fabricate metal products line by line and layer upon layer within a powder bed system. Such process allows the building of parts with customized shapes, which brings higher design flexibility than traditional casting and wrought manufacturing. In this work, AlSi10Mg powder is chosen as the raw material for producing parts by SLM, since aluminum alloys are widely used in automotive and aerospace industries thanks to an excellent combination of low density and competitive mechanical properties. However, there remain multiple drawbacks which limit further applications of aluminum parts produced by SLM: lack of prediction of solidification microstructure, few studies on fatigue properties, and cost and time caused by the limited production rate. All these issues were studied in this work and summarized as follows: Rapid movement of the melt pool (at a speed around 1 m/s) in SLM of metal powder directly implies rapid solidification. In this research, the length scale of the as-built microstructure of parts built with the alloy AlSi10Mg was measured and compared with the well-known relationship between cell size and cooling rate. Cooling rates during solidification were estimated using the Rosenthal equation. It was found that the solidification structure is the expected cellular combination of silicon with alpha-aluminum. The dependence of the measured cell spacing on the calculated cooling rate follows the well-established relationship for aluminum alloys. The implication is that cell spacing can be manipulated by changing the heat input. Microscopy of polished sections through particles of the metal powder used to build the parts showed that the particles have a dendritic-eutectic structure; the dendrite arm spacings in metal powder particles of different diameters were measured and also agree with literature correlations, showing the expected increase in secondary dendrite arm spacing with increasing particle diameter. It is well-known that the fatigue behavior of cast aluminum alloy parts is largely determined by the internal defects, particularly pores and inclusions, such as oxides. This study shows that such imperfections are also present in AlSi10Mg parts produced by SLM, and serve as sites for failure initiation. The effect of hatch spacing and building orientation on tensile and fatigue properties was tested. Similar defects were found both on polished cross-sections and on fracture surfaces. The results imply that the oxide-driven pores dominate the fatigue resistance of the samples in this work. The larger oxide particles which are associated with the crack initiation likely form by oxidation of metal vapor during part manufacture. Residual porosity in parts produced by SLM mainly results from lack-of-fusion, entrapped gas, pores left in powder, evaporation of elements, and collapse of key-holes. Lack-of-fusion porosity is caused by the the insufficient overlap of melt pools in powder bed fusion and is particularly detrimental to fatigue performance due to the stress concentration at the sharp edges of the pores. The third part of this work deals with predicting lack-of-fusion porosity quantitatively by a geometrically-based model and designing processing parameters for build rate improvement without introducing porosity. The inputs into the simulation are hatch spacing, layer thickness, melt-pool cross-sectional area, and hatch rotation angle. Comparison with several data sets from the literature shows that the simulations correctly predict process conditions at which lack-of-fusion porosity becomes apparent, as well as the rate at which porosity increases with changes in process conditions such as beam speed, layer thickness, and hatch spacing. Relative to the default processing parameters provided by the manufacturer, the build rate can be improved by adjusting hatch spacing and layer thickness, and increasing the platform temperature. The simulations also show that the volume fraction of lack-of-fusion porosity is independent of hatch rotation angle. A unique combination of zero rotation and half hatch spacing as the beam offset between adjacent layers is proposed for build rate optimization.

Material challenges for solar cells in the twenty-first century: directions in emerging technologies

PubMed Central

Delamarre, Amaury; Jehl, Zacharie; Suchet, Daniel; Cojocaru, Ludmila; Giteau, Maxime; Behaghel, Benoit; Julian, Anatole; Ibrahim, Camille; Tatry, Léa; Wang, Haibin; Kubo, Takaya; Uchida, Satoshi; Segawa, Hiroshi; Miyashita, Naoya; Tamaki, Ryo; Shoji, Yasushi; Yoshida, Katsuhisa; Ahsan, Nazmul; Watanabe, Kentaro; Inoue, Tomoyuki; Sugiyama, Masakazu; Nakano, Yoshiaki; Hamamura, Tomofumi; Toupance, Thierry; Olivier, Céline; Chambon, Sylvain; Vignau, Laurence; Geffroy, Camille; Cloutet, Eric; Hadziioannou, Georges; Cavassilas, Nicolas; Rale, Pierre; Cattoni, Andrea; Collin, Stéphane; Gibelli, François; Paire, Myriam; Lombez, Laurent; Aureau, Damien; Bouttemy, Muriel; Etcheberry, Arnaud; Okada, Yoshitaka

2018-01-01

Abstract Photovoltaic generation has stepped up within the last decade from outsider status to one of the important contributors of the ongoing energy transition, with about 1.7% of world electricity provided by solar cells. Progress in materials and production processes has played an important part in this development. Yet, there are many challenges before photovoltaics could provide clean, abundant, and cheap energy. Here, we review this research direction, with a focus on the results obtained within a Japan–French cooperation program, NextPV, working on promising solar cell technologies. The cooperation was focused on efficient photovoltaic devices, such as multijunction, ultrathin, intermediate band, and hot-carrier solar cells, and on printable solar cell materials such as colloidal quantum dots. PMID:29707072

The role of plant processing for the cancer preventive potential of Ethiopian kale (Brassica carinata).

PubMed

Odongo, Grace Akinyi; Schlotz, Nina; Herz, Corinna; Hanschen, Franziska S; Baldermann, Susanne; Neugart, Susanne; Trierweiler, Bernhard; Frommherz, Lara; Franz, Charles M A P; Ngwene, Benard; Luvonga, Abraham Wahid; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

2017-01-01

Background : Ethiopian kale ( Brassica carinata ) is a horticulturally important crop used as leafy vegetable in large parts of East and Southern Africa. The leaves are reported to contain high concentrations of health-promoting secondary plant metabolites. However, scientific knowledge on their health benefits is scarce. Objective : This study aimed to determine the cancer preventive potential of B. carinata using a human liver in vitro model focusing on processing effects on the pattern of secondary plant metabolites and bioactivity. Design : B. carinata was cultivated under controlled conditions and differentially processed (raw, fermented, or cooked) after harvesting. Human liver cancer cells (HepG2) were treated with ethanolic extracts of raw or processed B. carinata leaves and analyzed for their anti-genotoxic, anti-oxidant, and cytostatic potential. Chemical analyses were carried out on glucosinolates including breakdown products, phenolic compounds, carotenoids, and chlorophyll content. Results : Pre-treatment with B. carinata extracts concentration dependently reduced aflatoxin-induced DNA damage in the Comet assay, reduced the production of reactive oxygen species as determined by electron paramagnetic resonance spectroscopy, and induced Nrf2-mediated gene expression. Increasing extract concentrations also promoted cytostasis. Processing had a significant effect on the content of secondary plant metabolites. However, different processing methodologies did not dramatically decrease bioactivity, but enhanced the protective effect in some of the endpoints studied. Conclusion : Our findings highlight the cancer preventive potential of B. carinata as indicated by the protection of human liver cells against aflatoxin in vitro . In general, consumption of B. carinata should be encouraged as part of chemopreventive measures to combat prevalence of aflatoxin-induced diseases.

Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length.

PubMed

Liu, Shixuan; Ginzberg, Miriam Bracha; Patel, Nish; Hild, Marc; Leung, Bosco; Li, Zhengda; Chen, Yen-Chi; Chang, Nancy; Wang, Yuan; Tan, Ceryl; Diena, Shulamit; Trimble, William; Wasserman, Larry; Jenkins, Jeremy L; Kirschner, Marc W; Kafri, Ran

2018-03-29

Animal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity. © 2017, Liu et al.

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

PubMed

Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability.

PubMed

Myrand-Lapierre, Marie-Eve; Deng, Xiaoyan; Ang, Richard R; Matthews, Kerryn; Santoso, Aline T; Ma, Hongshen

2015-01-07

The extraordinary deformability of red blood cells gives them the ability to repeatedly transit through the microvasculature of the human body. The loss of this capability is part of the pathology of a wide range of diseases including malaria, hemoglobinopathies, and micronutrient deficiencies. We report on a technique for multiplexed measurements of the pressure required to deform individual red blood cell through micrometer-scale constrictions. This measurement is performed by first infusing single red blood cells into a parallel array of ~1.7 μm funnel-shaped constrictions. Next, a saw-tooth pressure waveform is applied across the constrictions to squeeze each cell through its constriction. The threshold deformation pressure is then determined by relating the pressure-time data with the video of the deformation process. Our key innovation is a self-compensating fluidic network that ensures identical pressures are applied to each cell regardless of its position, as well as the presence of cells in neighboring constrictions. These characteristics ensure the consistency of the measurement process and robustness against blockages of the constrictions by rigid cells and debris. We evaluate this technique using in vitro cultures of RBCs infected with P. falciparum, the parasite that causes malaria, to demonstrate the ability to profile the deformability signature of a heterogeneous sample.

The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health.

PubMed

Ibarguren, Maitane; López, David J; Escribá, Pablo V

2014-06-01

This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimer's and Parkinson's disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Kynurenine pathway metabolites and enzymes involved in redox reactions.

PubMed

González Esquivel, D; Ramírez-Ortega, D; Pineda, B; Castro, N; Ríos, C; Pérez de la Cruz, V

2017-01-01

Oxido-reduction reactions are a fundamental part of the life due to support many vital biological processes as cellular respiration and glucose oxidation. In the redox reactions, one substance transfers one or more electrons to another substance. An important electron carrier is the coenzyme NAD + , which is involved in many metabolic pathways. De novo biosynthesis of NAD + is through the kynurenine pathway, the major route of tryptophan catabolism, which is sensitive to redox environment and produces metabolites with redox capacity, able to alter biological functions that are controlled by redox-responsive signaling pathways. Kynurenine pathway metabolites have been implicated in the physiology process and in the physiopathology of many diseases; processes that also share others factors as dysregulation of calcium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation and cell death, which impact the redox environment. This review examines in detail the available evidence in which kynurenine pathway metabolites participate in redox reactions and their effect on cellular redox homeostasis, since the knowledge of the main factors and mechanisms that lead to cell death in many neurodegenative disorders and other pathologies, such as mitochondrial dysfunction, oxidative stress and kynurenines imbalance, will allow to develop therapies using them as targets. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Replication of adeno-associated virus in cells irradiated with UV light at 254 nm

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

Yakobson, B.; Hrynko, T.A.; Peak, M.J.

1989-03-01

Irradiation of simian virus 40 (ori mutant)-transformed Chinese hamster embryo cells (OD4 line) with UV light induced a cellular capacity which supported a full cycle of helper-independent adeno-associated virus replication. Monochromatic UV light at 254 nm was about 1,000-fold more effective than UV light at 313 nm, indicating that cellular nucleic acid is the primary chromophore in the UV-induced process leading to permissiveness for adeno-associated virus replication. The UV irradiation and the infection could be separated for up to 12 h without substantial loss of permissiveness. During this time interval, the induction process was partly sensitive to cycloheximide, suggesting amore » requirement for de novo protein synthesis.« less

Ultrastructure of extrusomes in hypotrichous ciliate Pseudourostyla nova

NASA Astrophysics Data System (ADS)

Zhou, Yao; Wang, Zhengjun; Zhang, Jun; Gu, Fukang

2011-01-01

The ultrastructure of extrusomes of the hypotrichous ciliate Pseudourostyla nova was observed in scanning and transmission electron microscopy and enzyme-cytochemistry. The results show that the distribution, morphological characteristics, morphogenesis process, and extrusive process of the extrusomes in P. nova are different from the trichocysts in Paramecium, suggesting that the extrusomes of P. nova can respond to environmental stimuli, play an important role in the defense of this species, and cannot be regarded as "trichocysts". The results also suggest that the extrusomes might be originated from the Golgi apparatus and mature in the cytoplasm; after the extrusion of mature extrusomes, the residual substance might be reabsorbed and reused by the ciliate cell via food vacuoles, and take part in material recycling of the cell.

[Signal reception and processing by the retina].

PubMed

Eysel, U

2007-01-01

Phototransduction occurs in the retina, which, as an outsourced part of the brain, fulfills important tasks in neuronal processing for image analysis relevant to perception. Interlinked biochemical cycles with immense amplification factors transform the electromagnetic waves of light into neuronal activity, and photochemical adaptation allows adjustment to light intensities of over more than 10 logarithmic units. Beginning with its dual system of photoreceptors with highly sensible rods and a color sensitive cone system, the retina, with between 50 and 100 main cell types, is characterized by complex neuronal circuits. The resulting center-surround antagonism of the receptive fields serves, amongst other things, to amplify intensity and color contrasts. Specialized ganglion cell types give rise to parallel signaling pathways into the higher visual centers of the brain.

Fundamentals and applications of solar energy. Part 2

NASA Astrophysics Data System (ADS)

Faraq, I. H.; Melsheimer, S. S.

Applications of techniques of chemical engineering to the development of materials, production methods, and performance optimization and evaluation of solar energy systems are discussed. Solar thermal storage systems using phase change materials, liquid phase Diels-Alder reactions, aquifers, and hydrocarbon oil were examined. Solar electric systems were explored in terms of a chlorophyll solar cell, the nonequilibrium electric field effects developed at photoelectrode/electrolyte interfaces, and designs for commercial scale processing of solar cells using continuous thin-film coating production methods. Solar coal gasification processes were considered, along with multilayer absorber coatings for solar concentrator receivers, solar thermal industrial applications, the kinetics of anaerobic digestion of crop residues to produce methane, and a procedure for developing a computer simulation of a solar cooling system.

Actin Engine in Immunological Synapse

PubMed Central

Piragyte, Indre

2012-01-01

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse. PMID:22916042

Six different roles for crossover inhibition in the retina: correcting the nonlinearities of synaptic transmission.

PubMed

Werblin, Frank S

2010-03-01

Early retinal studies categorized ganglion cell behavior as either linear or nonlinear and rectifying as represented by the familiar X- and Y-type ganglion cells in cat. Nonlinear behavior is in large part a consequence of the rectifying nonlinearities inherent in synaptic transmission. These nonlinear signals underlie many special functions in retinal processing, including motion detection, motion in motion, and local edge detection. But linear behavior is also required for some visual processing tasks. For these tasks, the inherently nonlinear signals are "linearized" by "crossover inhibition." Linearization utilizes a circuitry whereby nonlinear ON inhibition adds with nonlinear OFF excitation or ON excitation adds with OFF inhibition to generate a more linear postsynaptic voltage response. Crossover inhibition has now been measured in most bipolar, amacrine, and ganglion cells. Functionally crossover inhibition enhances edge detection, allows ganglion cells to recognize luminance-neutral patterns with their receptive fields, permits ganglion cells to distinguish contrast from luminance, and maintains a more constant conductance during the light response. In some cases, crossover extends the operating range of cone-driven OFF ganglion cells into the scotopic levels. Crossover inhibition is also found in neurons of the lateral geniculate nucleus and V1.

Accelerator mass spectrometry detection of beryllium ions in the antigen processing and presentation pathway

DOE PAGES

Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.; ...

2014-06-16

We report that exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstratemore » that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, we determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.« less

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

PubMed Central

Weeden, Clare E.; Chen, Yunshun; Ma, Stephen B.; Hu, Yifang; Ramm, Georg; Sutherland, Kate D.; Smyth, Gordon K.

2017-01-01

Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC. PMID:28125611

Finding the key - cell biology and science education.

PubMed

Miller, Kenneth R

2010-12-01

No international research community, cell biology included, can exist without an educational community to renew and replenish it. Unfortunately, cell biology researchers frequently regard their work as independent of the process of education and see little reason to reach out to science teachers. For cell biology to continue to prosper, I argue that researchers must support education in at least three ways. First, we must view education and research as part of a single scientific community. Second, we should take advantage of new technologies to connect the research laboratory to the classroom. Finally, we must take the initiative in defending the integrity of science teaching, particularly when education is under attack for political or religious reasons. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cell interactions in bone tissue engineering.

PubMed

Pirraco, R P; Marques, A P; Reis, R L

2010-01-01

Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

A comparative study of the annealing behavior of Cu(In,Ga)(S,Se){sub 2} based solar cells with an indium sulfide buffer layer, partly submitted to wet chemical treatments

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

Hönes, C., E-mail: christian.hoenes@de.bosch.com; Laboratory for Photovoltaics, University of Luxembourg, 41 rue du Brill, L-4422 Belvaux; Hackenberg, J.

2015-03-07

Indium sulfide thin films deposited via thermal evaporation from compound source material have been successfully utilized as a cadmium free buffer layer for Cu(In,Ga)Se{sub 2} based solar cells. However, high efficiencies are only reached after an additional annealing step. In this work, the annealing behavior of Cu(In,Ga)(S,Se){sub 2} based indium sulfide buffered solar cells is compared to the annealing behavior of similar cells, which were submitted to wet chemical treatments partly containing cadmium ions. Upon annealing a significant improvement of the initial solar cell characteristics is observed for the untreated cell and is related to the increase of activation energymore » for the carrier recombination process and a decrease of the ideality factor within the one diode model. It is shown here that this improvement can also be achieved by wet treatments of the absorber prior to buffer layer deposition. Upon annealing these treated cells still gain in collection length but lose open circuit voltage, which is explained here within a model including a highly p-doped absorber surface layer and supported by simulations showing that a decrease in doping density of such a surface layer would lead to the observed effects.« less

Finite Element Analysis of Single Cell Stiffness Measurements Using PZT-Integrated Buckling Nanoneedles.

PubMed

Rad, Maryam Alsadat; Tijjani, Auwal Shehu; Ahmad, Mohd Ridzuan; Auwal, Shehu Muhammad

2016-12-23

This paper proposes a new technique for real-time single cell stiffness measurement using lead zirconate titanate (PZT)-integrated buckling nanoneedles. The PZT and the buckling part of the nanoneedle have been modelled and validated using the ABAQUS software. The two parts are integrated together to function as a single unit. After calibration, the stiffness, Young's modulus, Poisson's ratio and sensitivity of the PZT-integrated buckling nanoneedle have been determined to be 0.7100 N·m -1 , 123.4700 GPa, 0.3000 and 0.0693 V·m·N -1 , respectively. Three Saccharomyces cerevisiae cells have been modelled and validated based on compression tests. The average global stiffness and Young's modulus of the cells are determined to be 10.8867 ± 0.0094 N·m -1 and 110.7033 ± 0.0081 MPa, respectively. The nanoneedle and the cell have been assembled to measure the local stiffness of the single Saccharomyces cerevisiae cells The local stiffness, Young's modulus and PZT output voltage of the three different size Saccharomyces cerevisiae have been determined at different environmental conditions. We investigated that, at low temperature the stiffness value is low to adapt to the change in the environmental condition. As a result, Saccharomyces cerevisiae becomes vulnerable to viral and bacterial attacks. Therefore, the proposed technique will serve as a quick and accurate process to diagnose diseases at early stage in a cell for effective treatment.

Studies on sintering additives for hydroxyapatite, and controlled porosity structures of calcium aluminates and polypropylene-tricalcium phosphate for bone graft applications

NASA Astrophysics Data System (ADS)

Kalita, Samar Jyoti

Tissue engineering has made a significant contribution in developing new biomaterials that can restore the structural features and physiological functions of natural tissues. Various materials, such as metals, ceramics, polymers and composites have been developed for their use in hard tissue engineering applications. Part A of this thesis describes my research on HAp ceramics. HAp, a bioactive ceramic, is known for its osteoconductivity, but shows poor mechanical performance. This program aimed at improving mechanical performance of synthetic HAp by introducing small quantities of various sintering additives. A range of oxide-based sintering additives were selected and prepared. Dense compacts were prepared using a uniaxial press with an average green density of 1.6 g/cc. Results showed that some of these sintering additives improved densification, hardness and compression strength of synthetic HAp compared to the pure composition. A maximum bulk density of 3.06 g/cc was achieved for 2.5 wt% addition of MgO. A Microhardness of 4.9 GPa (505 HV) was measured for 2.5 wt% addition of BaO, and the highest compression strength (220MPa) was reported for 2.5 wt% addition of CaO. Cytotoxicity and cell proliferation studies with a modified human osteoblast (HOB) cell-line (OPC1) proved most of these materials non-toxic and biocompatible. Microscopic observation revealed that bone cells were attached and grew well on most of these ceramic matrices. Part B describes my work on development of controlled porosity polypropylene-tricalcium phosphate composite scaffolds via the fused deposition modeling (FDM) process. Hg-porosimetry was performed to determine pore size and their distribution. Uniaxial compression testing performed on samples with 36 vol% porosity and pore size of 160 mum showed the best compressive strength of 12.7 MPa. Part C includes my research on development of "3-D honeycomb" porous calcium aluminate structures via the indirect FDM process. Samples of 29% and 44% VFP (designed) with average pore size of 300 mum showed compressive strength between 2 and 24 MPa. Cell proliferation studies conducted with OPC1 cells on polymer-ceramic composite scaffolds and porous calcium aluminate structures showed good cell attachment and a steady cell growth behavior during the first three weeks of in vitro analyses.

Use of hydrodynamic disintegration to accelerate anaerobic digestion of surplus activated sludge.

PubMed

Grübel, Klaudiusz; Machnicka, Alicja

2009-12-01

Hydrodynamic disintegration of activated sludge resulted in organic matter and polymers transfer from the solid phase into the liquid phase. Disintegration by hydrodynamic cavitation had a positive effect on the degree and rate of excess sludge anaerobic digestion. Also, addition of a part of anaerobic digested sludge containing adapted microorganisms resulted in acceleration of the process. The disruption of cells of foam microorganisms and addition to the digestion process led to an increase of biogas production.

Regulation of proximal-distal intercalation during limb regeneration in the axolotl (Ambystoma mexicanum).

PubMed

Satoh, Akira; Cummings, Gillian M C; Bryant, Susan V; Gardiner, David M

2010-12-01

Intercalation is the process whereby cells located at the boundary of a wound interact to stimulate proliferation and the restoration of the structures between the boundaries that were lost during wounding. Thus, intercalation is widely considered to be the mechanism of regeneration. When a salamander limb is amputated, the entire cascade of regeneration events is activated, and the missing limb segments and their boundaries (joints) as well as the structures within each segment are regenerated. Therefore, in an amputated limb it is not possible to distinguish between intersegmental regeneration (formation of new segments/joints) and intrasegmental regeneration (formation of structures within a given segment), and it is not possible to study the differential regulation of these two processes. We have used two models for regeneration that allow us to study these two processes independently, and report that inter- and intrasegmental regeneration are different processes regulated by different signaling pathways. New limb segments/joints can be regenerated from cells that dedifferentiate to form blastema cells in response to signaling that is mediated in part by fibroblast growth factor. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Developmental Biologists.

The role of printing techniques for large-area dye sensitized solar cells

NASA Astrophysics Data System (ADS)

Mariani, Paolo; Vesce, Luigi; Di Carlo, Aldo

2015-10-01

The versatility of printing technologies and their intrinsic ability to outperform other techniques in large-area deposition gives scope to revolutionize the photovoltaic (PV) manufacturing field. Printing methods are commonly used in conventional silicon-based PVs to cover part of the production process. Screen printing techniques, for example, are applied to deposit electrical contacts on the silicon wafer. However, it is with the advent of third generation PVs that printing/coating techniques have been extensively used in almost all of the manufacturing processes. Among all the third generation PVs, dye sensitized solar cell (DSSC) technology has been developed up to commercialization levels. DSSCs and modules can be fabricated by adopting all of the main printing techniques on both rigid and flexible substrates. This allows an easy tuning of cell/module characteristics to the desired application. Transparency, colour, shape, layout and other DSSC’s features can be easily varied by changing the printing parameters and paste/ink formulations used in the printing process. This review focuses on large-area printing/coating technologies for the fabrication of DSSCs devices. The most used and promising techniques are presented underlining the process parameters and applications.

The Efficiency of Dentin Sialoprotein-Phosphophoryn Processing Is Affected by Mutations Both Flanking and Distant from the Cleavage Site*

PubMed Central

Yang, Robert T.; Lim, Glendale L.; Dong, Zhihong; Lee, Arthur M.; Yee, Colin T.; Fuller, Robert S.; Ritchie, Helena H.

2013-01-01

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G447↓D448 cleavage site in DSP-PP240 had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P4 to P4′ blocked, impaired, or enhanced DSP-PP240 cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP240 had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP240 significantly modified the amount of PP240 product generated from DSP-PP240 precursor protein cleavage suggests that such mutation may affect the mineralization process. PMID:23297400

The efficiency of dentin sialoprotein-phosphophoryn processing is affected by mutations both flanking and distant from the cleavage site.

PubMed

Yang, Robert T; Lim, Glendale L; Dong, Zhihong; Lee, Arthur M; Yee, Colin T; Fuller, Robert S; Ritchie, Helena H

2013-02-22

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G(447)↓D(448) cleavage site in DSP-PP(240) had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P(4) to P(4)' blocked, impaired, or enhanced DSP-PP(240) cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP(240) had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP(240) significantly modified the amount of PP(240) product generated from DSP-PP(240) precursor protein cleavage suggests that such mutation may affect the mineralization process.

Combined inhibition of autophagy and caspases fails to prevent developmental nurse cell death in the Drosophila melanogaster ovary.

PubMed

Peterson, Jeanne S; McCall, Kimberly

2013-01-01

During the final stages of Drosophila melanogaster oogenesis fifteen nurse cells, sister cells to the oocyte, degenerate as part of normal development. This process involves at least two cell death mechanisms, caspase-dependent cell death and autophagy, as indicated by apoptosis and autophagy markers. In addition, mutations affecting either caspases or autophagy partially reduce nurse cell removal, leaving behind end-stage egg chambers with persisting nurse cell nuclei. To determine whether apoptosis and autophagy work in parallel to degrade and remove these cells as is the case with salivary glands during pupariation, we generated mutants doubly affecting caspases and autophagy. We found no significant increase in either the number of late stage egg chambers containing persisting nuclei or in the number of persisting nuclei per egg chamber in the double mutants compared to single mutants. These findings suggest that there is another cell death mechanism functioning in the ovary to remove all nurse cell remnants from late stage egg chambers.

Simulation of thermal stresses in anode-supported solid oxide fuel cell stacks. Part II: Loss of gas-tightness, electrical contact and thermal buckling

NASA Astrophysics Data System (ADS)

Nakajo, Arata; Wuillemin, Zacharie; Van herle, Jan; Favrat, Daniel

Structural stability issues in planar solid oxide fuel cells arise from the mismatch between the coefficients of thermal expansion of the components. The stress state at operating temperature is the superposition of several contributions, which differ depending on the component. First, the cells accumulate residual stresses due to the sintering phase during the manufacturing process. Further, the load applied during assembly of the stack to ensure electric contact and flatten the cells prevents a completely stress-free expansion of each component during the heat-up. Finally, thermal gradients cause additional stresses in operation. The temperature profile generated by a thermo-electrochemical model implemented in an equation-oriented process modelling tool (gPROMS) was imported into finite-element software (ABAQUS) to calculate the distribution of stress and contact pressure on all components of a standard solid oxide fuel cell repeat unit. The different layers of the cell in exception of the cathode, i.e. anode, electrolyte and compensating layer were considered in the analysis to account for the cell curvature. Both steady-state and dynamic simulations were performed, with an emphasis on the cycling of the electrical load. The study includes two different types of cell, operation under both thermal partial oxidation and internal steam-methane reforming and two different initial thicknesses of the air and fuel compressive sealing gaskets. The results generated by the models are presented in two papers: Part I focuses on cell cracking. In the present paper, Part II, the occurrences of loss of gas-tightness in the compressive gaskets and/or electrical contact in the gas diffusion layer were identified. In addition, the dependence on temperature of both coefficients of thermal expansion and Young's modulus of the metallic interconnect (MIC) were implemented in the finite-element model to compute the plastic deformation, while the possibilities of thermal buckling were analysed in a dedicated and separate model. The value of the minimum stable thickness of the MIC is large, even though significantly affected by the operating conditions. This phenomenon prevents any unconsidered decrease of the thickness to reduce the thermal inertia of the stack. Thermal gradients and the shape of the temperature profile during operation induce significant decreases of the contact pressure on the gaskets near the fuel manifold, at the inlet or outlet, depending on the flow configuration. On the contrary, the electrical contact was ensured independently of the operating point and history, even though plastic strain developed in the gas diffusion layer.

Optimization of cell seeding in a 2D bio-scaffold system using computational models.

PubMed

Ho, Nicholas; Chua, Matthew; Chui, Chee-Kong

2017-05-01

The cell expansion process is a crucial part of generating cells on a large-scale level in a bioreactor system. Hence, it is important to set operating conditions (e.g. initial cell seeding distribution, culture medium flow rate) to an optimal level. Often, the initial cell seeding distribution factor is neglected and/or overlooked in the design of a bioreactor using conventional seeding distribution methods. This paper proposes a novel seeding distribution method that aims to maximize cell growth and minimize production time/cost. The proposed method utilizes two computational models; the first model represents cell growth patterns whereas the second model determines optimal initial cell seeding positions for adherent cell expansions. Cell growth simulation from the first model demonstrates that the model can be a representation of various cell types with known probabilities. The second model involves a combination of combinatorial optimization, Monte Carlo and concepts of the first model, and is used to design a multi-layer 2D bio-scaffold system that increases cell production efficiency in bioreactor applications. Simulation results have shown that the recommended input configurations obtained from the proposed optimization method are the most optimal configurations. The results have also illustrated the effectiveness of the proposed optimization method. The potential of the proposed seeding distribution method as a useful tool to optimize the cell expansion process in modern bioreactor system applications is highlighted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ependymal cells variations in the central canal of the rat spinal cord filum terminale: an ultrastructural investigation.

PubMed

Mitro, A; Gallatz, K; Palkovits, M; Kiss, A

2013-04-01

The ependymal cells, considered today as an active participant in neuroendocrine functions, were investigated by electron microscopy in the central canal of the lowest spinal cord, the filum terminale (FT), in adult rats. In this area of the spinal cord, the central canal is covered by a heterogeneous population of ependymal cells. The aim of the present work was to compare the regional features of the ependymal cells in two different parts of the FT with a special regard to their ultrastructure. Two parts of the FT were selected for the ultrastructural observations: the rostral (rFT) and the caudal (cFT) ones. The rTF was removed at the level of the immediate continuation of the conus medullaris, while the cFT 30 mm further caudally. After formaldehyde fixation, the spinal cord was removed and cut into small blocks for electron microscopic processing. The material was embedded into durcupan, contrasted with uranyl acetate, lead citrate as well as osmium tetroxide, and investigated under JEOL 1200 EX electron microscope. In the rFT, the ependymal lining is pseudostratified and one-layered in the cFT, whereas the shape of the ependymal cells may vary from cuboidal to flatten in the rostro-caudal direction. The basal membrane of many ependymal cells possesses deep invaginations, so called "filum terminale labyrinths". Many neuronal processes occur in the pericanalicular neuropil. In contrast to the rFT, the cFT is less rich in the neuropil particles. Some of the ependymal cells concurrently reach both the intracanalicular and extracanalicular cerebrospinal fluid (CSF), thus they may represent a new variant of the ependymal cells designated as "bridge cells of the FT". The present data indicate that the FT ependymal cells exhibit clear differences in anatomy as well as ultrastructure that may reflect their distinct functional activity. Therefore, observations presented here may serve for the better understanding of the physiological role of the individual ependymal areas in this special portion of the rat spinal cord.

Climate Simulations based on a different-grid nested and coupled model

NASA Astrophysics Data System (ADS)

Li, Dan; Ji, Jinjun; Li, Yinpeng

2002-05-01

An atmosphere-vegetation interaction model (A VIM) has been coupled with a nine-layer General Cir-culation Model (GCM) of Institute of Atmospheic Physics/State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (IAP/LASG), which is rhomboidally truncated at zonal wave number 15, to simulate global climatic mean states. A VIM is a model having inter-feedback between land surface processes and eco-physiological processes on land. As the first step to couple land with atmosphere completely, the physiological processes are fixed and only the physical part (generally named the SVAT (soil-vegetation-atmosphere-transfer scheme) model) of AVIM is nested into IAP/LASG L9R15 GCM. The ocean part of GCM is prescribed and its monthly sea surface temperature (SST) is the climatic mean value. With respect to the low resolution of GCM, i.e., each grid cell having lon-gitude 7.5° and latitude 4.5°, the vegetation is given a high resolution of 1.5° by 1.5° to nest and couple the fine grid cells of land with the coarse grid cells of atmosphere. The coupling model has been integrated for 15 years and its last ten-year mean of outputs was chosen for analysis. Compared with observed data and NCEP reanalysis, the coupled model simulates the main characteris-tics of global atmospheric circulation and the fields of temperature and moisture. In particular, the simu-lated precipitation and surface air temperature have sound results. The work creates a solid base on coupling climate models with the biosphere.

The automated array assembly task of the low-cost silicon solar array project, phase 2

NASA Technical Reports Server (NTRS)

Coleman, M. G.; Pryor, R. A.; Sparks, T. G.; Legge, R.; Saltzman, D. L.

1980-01-01

Several specific processing steps as part of a total process sequence for manufacturing silicon solar cells were studied. Ion implantation was identified as the preferred process step for impurity doping. Unanalyzed beam ion implantation was shown to have major cost advantages over analyzed beam implantation. Further, high quality cells were fabricated using a high current unanalyzed beam. Mechanically masked plasma patterning of silicon nitride was shown to be capable of forming fine lines on silicon surfaces with spacings between mask and substrate as great as 250 micrometers. Extensive work was performed on advances in plated metallization. The need for the thick electroless palladium layer was eliminated. Further, copper was successfully utilized as a conductor layer utilizing nickel as a barrier to copper diffusion into the silicon. Plasma etching of silicon for texturing and saw damage removal was shown technically feasible but not cost effective compared to wet chemical etching techniques.

The Role of Sub- and Supercritical CO2 as "Processing Solvent" for the Recycling and Sample Preparation of Lithium Ion Battery Electrolytes.

PubMed

Nowak, Sascha; Winter, Martin

2017-03-06

Quantitative electrolyte extraction from lithium ion batteries (LIB) is of great interest for recycling processes. Following the generally valid EU legal guidelines for the recycling of batteries, 50 wt % of a LIB cell has to be recovered, which cannot be achieved without the electrolyte; hence, the electrolyte represents a target component for the recycling of LIBs. Additionally, fluoride or fluorinated compounds, as inevitably present in LIB electrolytes, can hamper or even damage recycling processes in industry and have to be removed from the solid LIB parts, as well. Finally, extraction is a necessary tool for LIB electrolyte aging analysis as well as for post-mortem investigations in general, because a qualitative overview can already be achieved after a few minutes of extraction for well-aged, apparently "dry" LIB cells, where the electrolyte is deeply penetrated or even gellified in the solid battery materials.

Biorefinery of microalgae - opportunities and constraints for different production scenarios.

PubMed

Hariskos, Ioanna; Posten, Clemens

2014-06-01

In order to design economically feasible production processes it is necessary, as part of the biorefinery concept, to valorize all constituents of the microalgal biomass. Such an approach requires appropriate biorefinery side-process strategies to be adapted to production of the primary product. These strategies are particularly valid for microalgae, since the composition and amount of residual biomass can vary significantly depending on cell stoichiometry and cultivation techniques. This review investigates opportunities and constraints for biorefinery concepts in production scenarios for four different products from microalgae with different market volumes, including high- and medium-value products, whole cells and biodiesel. Approaches to close material and energy balances, as well as to adapt the biorefinery according to biological potential, process routes, and market needs are presented, which will further contribute to making the biorefinery concept a success. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Introduction.

PubMed

Tepikin, Alexei V

2017-01-01

In the title of this part of the book, the tail is wagging not just in a single dog but multiple dogs; in other words, a single process SOCE (tail) somehow involves a cross talk of (wagging) large and powerful organelle and cellular compartments (dogs). So how is this possible? Is this really necessary? Is the title actually appropriate?SOCE is a rather special process, it allows efficient signaling based on a ubiquitous second messenger (Ca 2+ ) in multiple cell and tissue types, it has specific signaling modality (i.e., some downstream reactions depend specifically on SOCE and not just on global Ca 2+ increase), it is vital for the normal functioning of multiple types of cells and tissues, and when misregulated it induces important pathological processes. The reader hopefully agree that such an important "tail" is more appropriate for a kangaroo than for a Chihuahua and that it has awesome wagging capacity.

Membrane-less microfiltration using inertial microfluidics

PubMed Central

Warkiani, Majid Ebrahimi; Tay, Andy Kah Ping; Guan, Guofeng; Han, Jongyoon

2015-01-01

Microfiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10–20 μm) and yeast (3–5 μm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost, and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes. PMID:26154774

Connecting single cell to collective cell behavior in a unified theoretical framework

NASA Astrophysics Data System (ADS)

George, Mishel; Bullo, Francesco; Campàs, Otger

Collective cell behavior is an essential part of tissue and organ morphogenesis during embryonic development, as well as of various disease processes, such as cancer. In contrast to many in vitro studies of collective cell migration, most cases of in vivo collective cell migration involve rather small groups of cells, with large sheets of migrating cells being less common. The vast majority of theoretical descriptions of collective cell behavior focus on large numbers of cells, but fail to accurately capture the dynamics of small groups of cells. Here we introduce a low-dimensional theoretical description that successfully captures single cell migration, cell collisions, collective dynamics in small groups of cells, and force propagation during sheet expansion, all within a common theoretical framework. Our description is derived from first principles and also includes key phenomenological aspects of cell migration that control the dynamics of traction forces. Among other results, we explain the counter-intuitive observations that pairs of cells repel each other upon collision while they behave in a coordinated manner within larger clusters.

[Programmed necrosis and necroptosis - molecular mechanisms].

PubMed

Giżycka, Agata; Chorostowska-Wynimko, Joanna

2015-12-16

Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Roles and regulations of the ETS transcription factor ELF4/MEF

PubMed Central

Suico, Mary Ann; Shuto, Tsuyoshi; Kai, Hirofumi

2017-01-01

Abstract Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family—myeloid elf-1-like factor (MEF), designated as ELF4—has been shown to be critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence. ELF4 carries out these functions as a transcriptional activator or through interactions with its partner proteins. Mutations in ELF4 cause aberrant interactions and induce downstream processes that may lead to diseased cells. Knowing how ELF4 impinges on certain cellular processes and how it is regulated in the cells can lead to a better understanding of the physiological and pathological consequences of modulated ELF4 activity. PMID:27932483

Assembly line plants take root

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

Comis, D.; Wood, M.

This paper discussed tissue-culture propagation of sugarcane, apple trees, peach trees, citrus, orchids, data palms, and carrots. Tissue-culture propagation is a term used for a variety of techniques used to grow or genetically modify, preserve, or study plant parts in laboratories, from tissue or even a single cell. The author examined the benefits and commercial applications of this propagation process.

75 FR 61148 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... Evaluation and testing within a risk management process 2-100 ASTM E1372-95 (2003) Standard Test Method...) Standard Title, Type of Test Method for Agar Diffusion Cell standard , Relevant Culture Screening for... Biological evaluation of medical devices - Office(s) and Part 3: Tests for genotoxicity, Division(s...

Enzymatic hydrolysis of loblolly pine: effects of cellulose crystallinity and delignification

Treesearch

Umesh P. Agarwal; J.Y. Zhu; Sally A. Ralph

2013-01-01

Hydrolysis experiments with commercial cellulases have been performed to understand the effects of cell wall crystallinity and lignin on the process. In the focus of the paper are loblolly pine wood samples, which were systematically delignified and partly ball-milled, and, for comparison, Whatman CC31 cellulose samples with different crystallinities. In pure cellulose...

Measuring mitotic spindle dynamics in budding yeast

NASA Astrophysics Data System (ADS)

Plumb, Kemp

In order to carry out its life cycle and produce viable progeny through cell division, a cell must successfully coordinate and execute a number of complex processes with high fidelity, in an environment dominated by thermal noise. One important example of such a process is the assembly and positioning of the mitotic spindle prior to chromosome segregation. The mitotic spindle is a modular structure composed of two spindle pole bodies, separated in space and spanned by filamentous proteins called microtubules, along which the genetic material of the cell is held. The spindle is responsible for alignment and subsequent segregation of chromosomes into two equal parts; proper spindle positioning and timing ensure that genetic material is appropriately divided amongst mother and daughter cells. In this thesis, I describe fluorescence confocal microscopy and automated image analysis algorithms, which I have used to observe and analyze the real space dynamics of the mitotic spindle in budding yeast. The software can locate structures in three spatial dimensions and track their movement in time. By selecting fluorescent proteins which specifically label the spindle poles and cell periphery, mitotic spindle dynamics have been measured in a coordinate system relevant to the cell division. I describe how I have characterised the accuracy and precision of the algorithms by simulating fluorescence data for both spindle poles and the budding yeast cell surface. In this thesis I also describe the construction of a microfluidic apparatus that allows for the measurement of long time-scale dynamics of individual cells and the development of a cell population. The tools developed in this thesis work will facilitate in-depth quantitative analysis of the non-equilibrium processes in living cells.

Predicting the ultimate potential of natural gas SOFC power cycles with CO2 capture - Part B: Applications

NASA Astrophysics Data System (ADS)

Campanari, Stefano; Mastropasqua, Luca; Gazzani, Matteo; Chiesa, Paolo; Romano, Matteo C.

2016-09-01

An important advantage of solid oxide fuel cells (SOFC) as future systems for large scale power generation is the possibility of being efficiently integrated with processes for CO2 capture. Focusing on natural gas power generation, Part A of this work assessed the performances of advanced pressurised and atmospheric plant configurations (SOFC + GT and SOFC + ST, with fuel cell integration within a gas turbine or a steam turbine cycle) without CO2 separation. This Part B paper investigates such kind of power cycles when applied to CO2 capture, proposing two ultra-high efficiency plant configurations based on advanced intermediate-temperature SOFCs with internal reforming and low temperature CO2 separation process. The power plants are simulated at the 100 MW scale with a set of realistic assumptions about FC performances, main components and auxiliaries, and show the capability of exceeding 70% LHV efficiency with high CO2 capture (above 80%) and a low specific primary energy consumption for the CO2 avoided (1.1-2.4 MJ kg-1). Detailed results are presented in terms of energy and material balances, and a sensitivity analysis of plant performance is developed vs. FC voltage and fuel utilisation to investigate possible long-term improvements. Options for further improvement of the CO2 capture efficiency are also addressed.

3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads.

PubMed

Lehmann, R; Gallert, C; Roddelkopf, T; Junginger, S; Wree, A; Thurow, K

2016-08-01

Cancer diseases are a common problem of the population caused by age and increased harmful environmental influences. Herein, new therapeutic strategies and compound screenings are necessary. The regular 2D cultivation has to be replaced by three dimensional cell culturing (3D) for better simulation of in vivo conditions. The 3D cultivation with alginate matrix is an appropriate method for encapsulate cells to form cancer constructs. The automated manufacturing of alginate beads might be an ultimate method for large-scaled manufacturing constructs similar to cancer tissue. The aim of this study was the integration of full automated systems for the production, cultivation and screening of 3D cell cultures. We compared the automated methods with the regular manual processes. Furthermore, we investigated the influence of antibiotics on these 3D cell culture systems. The alginate beads were formed by automated and manual procedures. The automated steps were processes by the Biomek(®) Cell Workstation (celisca, Rostock, Germany). The proliferation and toxicity were manually and automatically evaluated at day 14 and 35 of cultivation. The results visualized an accumulation and expansion of cell aggregates over the period of incubation. However, the proliferation and toxicity were faintly and partly significantly decreased on day 35 compared to day 14. The comparison of the manual and automated methods displayed similar results. We conclude that the manual production process could be replaced by the automation. Using automation, 3D cell cultures can be produced in industrial scale and improve the drug development and screening to treat serious illnesses like cancer.

Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity.

PubMed

Kriete, Andres; Mayo, Kelli L; Yalamanchili, Nirupama; Beggs, William; Bender, Patrick; Kari, Csaba; Rodeck, Ulrich

2008-07-16

Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years. Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains obtained from older donors. We also observed enhanced NF-kappaB DNA binding activity in a subset of strains, and the NF-kappaB profile correlated with mRNA expression levels characteristic of inflammatory processes, which include transcripts coding for cytokines, chemokines, components of the complement cascade and MHC molecules. This intrinsic low-grade inflammatory state, as it relates to aging, occurs in cultured cells irrespective of the presence of other cell types or the in vivo context. Our results are consistent with the view that constitutive activation of inflammatory pathways is a phenomenon prevalent in aged fibroblasts. It is possibly part of a cellular survival process in response to compromised mitochondrial function. Importantly, the inflammatory gene expression signature described here is cell autonomous, i.e. occurs in the absence of prototypical immune or pro-inflammatory cells, growth factors, or other inflammatory mediators.

Towards programming languages for genetic engineering of living cells

PubMed Central

Pedersen, Michael; Phillips, Andrew

2009-01-01

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts. PMID:19369220

Towards programming languages for genetic engineering of living cells.

PubMed

Pedersen, Michael; Phillips, Andrew

2009-08-06

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.

FULL SCALE BIOREACTOR LANDFILL FOR CARBON SEQUESTRATION AND GREENHOUSE EMISSION CONTROL

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

Ramin Yazdani; Jeff Kieffer; Heather Akau

2003-08-01

The Yolo County Department of Planning and Public Works is constructing a full-scale bioreactor landfill as a part of the Environmental Protection Agency's (EPA) Project XL program to develop innovative approaches for carbon sequestration and greenhouse emission control. The overall objective is to manage landfill solid waste for rapid waste decomposition and maximum landfill gas generation and capture for carbon sequestration and greenhouse emission control. Waste decomposition is accelerated by improving conditions for either the aerobic or anaerobic biological processes and involves circulating controlled quantities of liquid (leachate, groundwater, gray water, etc.), and, in the aerobic process, large volumes ofmore » air. The first phase of the project entails the construction of a 12-acre module that contains a 6-acre anaerobic cell, a 3.5-acre anaerobic cell, and a 2.5-acre aerobic cell at the Yolo County Central Landfill near Davis, California. The cells are highly instrumented to monitor bioreactor performance. Liquid addition has commenced in the 3.5-acre anaerobic cell and the 6-acre anaerobic cell. Construction of the 2.5-acre aerobic cell is nearly complete with only the biofilter remaining and is scheduled to be complete by the end of August 2003. The current project status and preliminary monitoring results are summarized in this report.« less

Novel production method and in-vitro cell compatibility of porous Ti-6Al-4V alloy disk for hard tissue engineering.

PubMed

Bhattarai, Shanta Raj; Khalil, Khalil Abdel-Razek; Dewidar, Montasser; Hwang, Pyoung Han; Yi, Ho Keun; Kim, Hak Yong

2008-08-01

Porous metals are attractive due to its unique physical, mechanical, and new bone tissue ingrowth properties. In the present study, the production of highly porous Ti-6Al-4V parts by powder metallurgical technology and subsequently it's uses in in vitro bone tissue engineering is described. A space-holder method using carbamide with different particle size to produce parts with porosities between 35 and 70% were applied. The compressive strength and Young's modulus of porous Ti-6Al-4V were determined. Results indicated that stress and Young's modulus decrease with increasing porosity and pore size. The porous parts are characterized by scanning electron microscopy. Furthermore, study was to investigate the effects of three different porosities of porous Ti-6Al-4V (35, 50, and 70%) on proliferation, differentiation, and cell-matrix interaction of mouse osteoblast-like cells, MC-3T3. Results showed that the cell proliferation was significantly (p < 0.05) higher on 70% porous Ti-6Al-4V. However, synthesis of different types of extra cellular matrix proteins was also more abundant on 70% porous Ti-6Al-4V than 35 and 50% porous Ti-6Al-4V disk except some specific proteins. An increase in alkaline phosphate activity was significantly (p < 0.05) higher on 70 and 50% porous Ti-6Al-4V disk after 12 days of MC-3T3 cells incubation. Above all, results indicated that porosity (nearly 70%) of porous Ti-6Al-4V topography affects proliferation and differentiation of osteoblast-like MC-3T3 cells. The results showed that this novel process is a promise to fabricate porous biomaterials for bone implants.

Immunocytochemical localization of choline acetyltransferase and muscarinic ACh receptors in the antenna during development of the sphinx moth Manduca sexta.

PubMed

Clark, Julie; Meisner, Shannon; Torkkeli, Päivi H

2005-04-01

Immunocytochemistry with monoclonal antibodies was used to investigate the locations of muscarinic acetylcholine receptors (mAChR) and choline acetyltransferase (ChAT) in sections of the developing antennae of the moth Manduca sexta. The results were correlated with a previous morphological investigation in the developing antennae which allowed us to locate different cell types at various stages of development. Our findings indicated that the muscarinic cholinergic system was not restricted to the sensory neurons but was also present in glial and epidermal cells. By day 4-5 of adult development, immunoreactivity against both antibodies was present in the axons of the antennal nerve, and more intense labeling was present in sections from older pupae. At days 4-9, the cell bodies of the sensory neurons in the basal part of the epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature flagella, large numbers of cells, some with processes into hairs, were strongly labeled by both antibodies. Antennal glial cells were intensely immunolabeled with both antibodies by days 4-5, but in later stages, it was not possible to discriminate between glial and neural staining. At days 4-9, we observed a distinctly labeled layer of epidermal cells close to the developing cuticle. The expression of both ChAT and mAChRs by neurons in moth antennae may allow the regulation of excitability by endogenous ACh. Cholinergic communication between neurons and glia may be part of the system that guides axon elongation during development. The cholinergic system in the apical part of the developing epidermis could be involved in cuticle formation.

The cells of cajal-retzius: still a mystery one century after.

PubMed

Soriano, Eduardo; Del Río, José Antonio

2005-05-05

Cajal-Retzius (CR) cells are an enigmatic class of neurons located at the surface of the cerebral cortex, playing a major role in cortical development. In this review, we discuss several distinct features of these neurons and the mechanisms by which they regulate cortical development. Many CR cells likely have extracortical origin and undergo cell death during development. Recent genetic studies report unique patterns of gene expression in CR cells, which may help to explain the developmental processes in which they participate. Moreover, a number of studies indicate that CR cells, and their secreted gene product, reelin, are involved in neuronal migration by acting on two key partners, migrating neurons and radial glial cells. Emerging data show that these neurons are a critical part of an early and complex network of neural activity in layer I, supporting the notion that CR cells modulate cortical maturation. Given these key and complex developmental properties, it is therefore conceivable for CR cells to be implicated in the pathogenesis of a variety of neurological disorders.

Developmental Regulation of a Plasma Membrane Arabinogalactan Protein Epitope in Oilseed Rape Flowers.

PubMed Central

Pennell, RI; Janniche, L; Kjellbom, P; Scofield, GN; Peart, JM; Roberts, K

1991-01-01

We have identified and characterized the temporal and spatial regulation of a plasma membrane arabinogalactan protein epitope during development of the aerial parts of oilseed rape using the monoclonal antibody JIM8. The JIM8 epitope is expressed by the first cells of the embryo and by certain cells in the sexual organs of flowers. During embryogenesis, the JIM8 epitope ceases to be expressed by the embryo proper but is still found in the suspensor. During differentiation of the stamens and carpels, expression of the JIM8 epitope progresses from one cell type to another, ultimately specifying the endothecium and sperm cells, the nucellar epidermis, synergid cells, and the egg cell. This complex temporal sequence demonstrates rapid turnover of the JIM8 epitope. There is no direct evidence for any cell-inductive process in plant development. However, if cell-cell interactions exist in plants and participate in flower development, the JIM8 epitope may be a marker for one set of them. PMID:12324592

Live-cell confocal microscopy and quantitative 4D image analysis of anchor cell invasion through the basement membrane in C. elegans

PubMed Central

Kelley, Laura C.; Wang, Zheng; Hagedorn, Elliott J.; Wang, Lin; Shen, Wanqing; Lei, Shijun; Johnson, Sam A.; Sherwood, David R.

2018-01-01

Cell invasion through basement membrane (BM) barriers is crucial during development, leukocyte trafficking, and for the spread of cancer. Despite its importance in normal and diseased states, the mechanisms that direct invasion are poorly understood, in large part because of the inability to visualize dynamic cell-basement membrane interactions in vivo. This protocol describes multi-channel time-lapse confocal imaging of anchor cell invasion in live C. elegans. Methods presented include outline slide preparation and worm growth synchronization (15 min), mounting (20 min), image acquisition (20-180 min), image processing (20 min), and quantitative analysis (variable timing). Images acquired enable direct measurement of invasive dynamics including invadopodia formation, cell membrane protrusions, and BM removal. This protocol can be combined with genetic analysis, molecular activity probes, and optogenetic approaches to uncover molecular mechanisms underlying cell invasion. These methods can also be readily adapted for real-time analysis of cell migration, basement membrane turnover, and cell membrane dynamics by any worm laboratory. PMID:28880279

Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells

PubMed Central

Suzuki, Ayumu; Hirasaki, Masataka; Hishida, Tomoaki; Wu, Jun; Okamura, Daiji; Ueda, Atsushi; Nishimoto, Masazumi; Nakachi, Yutaka; Mizuno, Yosuke; Okazaki, Yasushi; Matsui, Yasuhisa; Belmonte, Juan Carlos Izpisua; Okuda, Akihiko

2016-01-01

Meiosis is a unique process that allows the generation of reproductive cells. It remains largely unknown how meiosis is initiated in germ cells and why non-germline cells do not undergo meiosis. We previously demonstrated that knockdown of Max expression, a gene encoding a partner of MYC family proteins, strongly activates expression of germ cell-related genes in ESCs. Here we find that complete ablation of Max expression in ESCs results in profound cytological changes reminiscent of cells undergoing meiotic cell division. Furthermore, our analyses uncovers that Max expression is transiently attenuated in germ cells undergoing meiosis in vivo and its forced reduction induces meiosis-like cytological changes in cultured germline stem cells. Mechanistically, Max depletion alterations are, in part, due to impairment of the function of an atypical PRC1 complex (PRC1.6), in which MAX is one of the components. Our data highlight MAX as a new regulator of meiotic onset. PMID:27025988

Advanced Cell Culture Techniques for Cancer Drug Discovery

PubMed Central

Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

2014-01-01

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

Advanced cell culture techniques for cancer drug discovery.

PubMed

Lovitt, Carrie J; Shelper, Todd B; Avery, Vicky M

2014-05-30

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

Behavior and function of paternally inherited centrioles in brown algal zygotes.

PubMed

Nagasato, Chikako

2005-12-01

In brown algal cells, the centrosome, consisting of a pair of centrioles and the pericentriolar material, is primarily involved in the organization of microtubules (MTs) throughout the cell cycle. In motile cells, the centrioles participate in the formation of flagellar axoneme as flagellar basal bodies, and in somatic cells they play a crucial role in many cellular activities as a part of the centrosome. With respect to the role of the centrosome as a microtubule organizing center (MTOC), brown algal cells resemble animal cells. In most animal fertilization processes, the sperm cell introduces centrioles, the core of the centrosome, into the egg cytoplasm. In this study, the behavior of centrioles from gametogenesis and fertilization to the first cell division of the zygote was examined in the three sexual reproduction patterns occurring in brown algae, i.e., oogamy, anisogamy and isogamy, by electron- and immunofluorescence-microscopy. The pair of centrioles contained in somatic cells was shown to be derived from the male gamete, irrespective of the sexual reproductive pattern. The paternally derived centrioles were duplicated before mitosis and were involved in spindle pole formation. Moreover, MTs from the centrosome play a crucial role in the process of cytokinesis, as the position of centrosomes accompanying daughter nuclei seems to determine the cytokinetic plane. A new approach to clarifying the mode of cytokinesis in brown algae is presented in this study.

Extracellular cell stress (heat shock) proteins-immune responses and disease: an overview.

PubMed

Pockley, A Graham; Henderson, Brian

2018-01-19

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

Segmentation of whole cells and cell nuclei from 3-D optical microscope images using dynamic programming.

PubMed

McCullough, D P; Gudla, P R; Harris, B S; Collins, J A; Meaburn, K J; Nakaya, M A; Yamaguchi, T P; Misteli, T; Lockett, S J

2008-05-01

Communications between cells in large part drive tissue development and function, as well as disease-related processes such as tumorigenesis. Understanding the mechanistic bases of these processes necessitates quantifying specific molecules in adjacent cells or cell nuclei of intact tissue. However, a major restriction on such analyses is the lack of an efficient method that correctly segments each object (cell or nucleus) from 3-D images of an intact tissue specimen. We report a highly reliable and accurate semi-automatic algorithmic method for segmenting fluorescence-labeled cells or nuclei from 3-D tissue images. Segmentation begins with semi-automatic, 2-D object delineation in a user-selected plane, using dynamic programming (DP) to locate the border with an accumulated intensity per unit length greater that any other possible border around the same object. Then the two surfaces of the object in planes above and below the selected plane are found using an algorithm that combines DP and combinatorial searching. Following segmentation, any perceived errors can be interactively corrected. Segmentation accuracy is not significantly affected by intermittent labeling of object surfaces, diffuse surfaces, or spurious signals away from surfaces. The unique strength of the segmentation method was demonstrated on a variety of biological tissue samples where all cells, including irregularly shaped cells, were accurately segmented based on visual inspection.

Ikaros promotes rearrangement of TCR alpha genes in an Ikaros null thymoma cell line

PubMed Central

Collins, Bernard; Clambey, Eric T.; Scott-Browne, James; White, Janice; Marrack, Philippa; Hagman, James; Kappler, John W.

2014-01-01

Summary Ikaros is important in the development and maintenance of the lymphoid system, functioning in part by associating with chromatin-remodeling complexes. We have studied the functions of Ikaros in the transition from pre-T cell to the CD4+CD8+ thymocyte using an Ikaros null CD4−CD8− mouse thymoma cell line (JE131). We demonstrate that this cell line carries a single functional TCR β gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry non-functional rearrangements on both alleles of their TCR α loci. Retroviral re-introduction of Ikaros dramatically increased the rate of transcription in the α locus and TCR Vα/Jα recombination resulting in the appearance of many new αβTCR+ cells. The process is RAG dependent, requires SWI/SNF chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR α enhancer. Furthermore, knockdown of Mi2/NuRD complexes increased the frequency of TCR α rearrangement. Our data suggest that Ikaros controls Vα/Jα recombination in T cells by controlling access of the transcription and recombination machinery to the TCR α loci. The JE131 cell line should prove to be a very useful tool for studying the molecular details of this and other processes involved in the pre-T cell to αβTCR+ CD4+CD8+ thymocyte transition. PMID:23172374

3-D Reconstruction of Macular Type II Cell Innervation Patterns in Space-Flight and Control Rats

NASA Technical Reports Server (NTRS)

Ross, Muriel Dorothy; Montgomery, K.; Linton, S.; Cheng, R.; Tomko, David L. (Technical Monitor)

1995-01-01

A semiautomated method for reconstructing objects from serial thin sections has been developed in the Biocomputation Center. The method is being used to completely, for the first time, type II hair cells and their innervations. The purposes are to learn more about the fundamental circuitry of the macula on Earth and to determine whether changes in connectivities occur under space flight conditions. Data captured directly from a transmission electron microscope via a video camera are sent to a graphics workstation. There, the digitized micrographs are mosaicked into sections and contours are traced, registered and displayed by semiautomated methods. Current reconstructions are of type II cells from the medial part of rat maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that typical type II cells receive processes from tip to six nearby calyces or afferents. Nearly all processes are elongated and have bouton-like enlargements; some have numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approximately 1/3 of the processes innervale 2 or 3 type II cells or a neighboring cluster. From 2% to 6% of the cells resemble type I cells morphologically but have demi-calyces. Thus far, increments in synaptic number in type II cells of flight rats are prominent along processes that supply two hair cells. It is clear that reconstruction methods provide insights into details of macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields through feed back-feed forward connections, and for dynamic alterations in receptive field range and activity during preprocessing of linear acceleratory information by the maculas. The reconstruction method we have developed will find further applications in the study of the details of neuronal architecture of more complex systems, to seek out shared organizational properties or neuronal networks and to understand better localization of synaptic changes in altered environments.

Cell therapy: a therapeutic alternative to treat focal cartilage lesions.

PubMed

Gimeno, M J; Maneiro, E; Rendal, E; Ramallal, M; Sanjurjo, L; Blanco, F J

2005-11-01

Human mesenchymal stem cells (MSCs) are present in most of the tissue matrix, taking part in their regeneration when injury or damage occurs. The aim of this study was to investigate the presence of cells with pluripotential characteristics in synovial membranes from osteoarthritic (OA) patients and the capacity of these cells to differentiate to chondrocytes. Synovial membranes (n = 8) from OA patients were digested with collagenase. Isolated cells were cultured with DMEM, 20% FBS, and FGFb10 ng/mL. Cells from second subculture were used to carry out phenotypic characterization experiments (flow cytometry analysis with 11 monoclonal antibodies) and chondrogenic differentiation experiments(micropellet cultured in chondrogenic medium). Chondrogenic differentiation of cells was assessment by quantification of cartilage extracellular matrix components by following techniques: Safranin O, Toluidine Blue, and Alcian Blue stains to detect proteoglycans and immunohistochemistry to detect type I and II collagen. Flow cytometry analyses showed that in our population more than 90% of cells were positive for MSC markers: CD29 (95%), CD44 (90%), CD73 (95%), CD90 (98%). Cells were negative for hematopoietic markers (CD11b, CD34, and CD45). Furthermore, cells showed positive stain to multipotent markers such as CD117 (c-kit) (98%), CD166 (74%), and STRO-1 (88%) and to quiescent satellite cells like PAX-7 (35%). The micropellet analyses showed that the culture of these cells with TGFbeta-3 for 2 and 3 weeks stimulates proteoglycan and collagen type II synthesis. Both molecules are characteristic of hyaline articular cartilage. In this work, we demonstrate the presence of a cellular population with MSC characteristics in synovial tissue from OA patients. As MSC takes part in reparative processes of adult tissues, these cells could play an important role in OA pathogenesis and treatment.

Biologic Activity of Autologous, Granulocyte-Macrophage Colony Stimulating Factor Secreting Alveolar Soft Parts Sarcoma and Clear Cell Sarcoma Vaccines

PubMed Central

Goldberg, John; Fisher, David E.; Demetri, George D.; Neuberg, Donna; Allsop, Stephen A.; Fonseca, Catia; Nakazaki, Yukoh; Nemer, David; Raut, Chandrajit P.; George, Suzanne; Morgan, Jeffrey A.; Wagner, Andrew J.; Freeman, Gordon J.; Ritz, Jerome; Lezcano, Cecilia; Mihm, Martin; Canning, Christine; Hodi, F. Stephen; Dranoff, Glenn

2015-01-01

Purpose Alveolar soft parts sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Experimental Design Metastatic tumors from ASPS and CCS patients were resected, processed to single cell suspensions, transduced with a replication defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly times three and then every other week. Results Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from 3 to 13 immunizations. Toxicities were restricted to grade 1–2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell mediated delayed type-hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1) positive CD8+ T cells in association with PD ligand-1 (PD-L1) expressing sarcoma cells. No tumor regressions were observed. Conclusions Vaccination with irradiated, GM-CSF secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1 negative regulatory pathway might intensify immune-mediated tumor destruction. PMID:25805798

Droplet-based microfluidic analysis and screening of single plant cells.

PubMed

Yu, Ziyi; Boehm, Christian R; Hibberd, Julian M; Abell, Chris; Haseloff, Jim; Burgess, Steven J; Reyna-Llorens, Ivan

2018-01-01

Droplet-based microfluidics has been used to facilitate high-throughput analysis of individual prokaryote and mammalian cells. However, there is a scarcity of similar workflows applicable to rapid phenotyping of plant systems where phenotyping analyses typically are time-consuming and low-throughput. We report on-chip encapsulation and analysis of protoplasts isolated from the emergent plant model Marchantia polymorpha at processing rates of >100,000 cells per hour. We use our microfluidic system to quantify the stochastic properties of a heat-inducible promoter across a population of transgenic protoplasts to demonstrate its potential for assessing gene expression activity in response to environmental conditions. We further demonstrate on-chip sorting of droplets containing YFP-expressing protoplasts from wild type cells using dielectrophoresis force. This work opens the door to droplet-based microfluidic analysis of plant cells for applications ranging from high-throughput characterisation of DNA parts to single-cell genomics to selection of rare plant phenotypes.

Ascorbic Acid Efflux and Re-uptake in Endothelial Cells: Maintenance of Intracellular Ascorbate

PubMed Central

May, James M.; Qu, Zhi-chao

2013-01-01

Entry of vitamin C or ascorbate into most tissues requires its movement across the endothelial cell barrier of vessels. If trans-cellular ascorbate movement occurs, then it should be evident as ascorbate efflux from endothelial cells. Cultured EA.926 endothelial cells that had been loaded to about 3.5 mM intracellular ascorbate lost 70–80% of ascorbate to the medium over several hours at 37 °C via a non-saturable process that was insensitive to anion transport inhibitors and thiol reagents. Oxidation of this extracellular ascorbate by ascorbate oxidase or ferricyanide enhanced apparent ascorbate efflux, suggesting that efflux of the vitamin was countered in part by its re-uptake on ascorbate transporters. Although basal ascorbate efflux was not calcium-dependent, increased entry of calcium into the cells enhanced ascorbate release. These results support the hypothesis that ascorbate efflux reflects trans-endothelial cell ascorbate movement out of the blood vessel. PMID:19148707

Ascorbic acid efflux and re-uptake in endothelial cells: maintenance of intracellular ascorbate.

PubMed

May, James M; Qu, Zhi-chao

2009-05-01

Entry of vitamin C or ascorbate into most tissues requires its movement across the endothelial cell barrier of vessels. If trans-cellular ascorbate movement occurs, then it should be evident as ascorbate efflux from endothelial cells. Cultured EA.926 endothelial cells that had been loaded to about 3.5 mM intracellular ascorbate lost 70-80% of ascorbate to the medium over several hours at 37 degrees C via a non-saturable process that was insensitive to anion transport inhibitors and thiol reagents. Oxidation of this extracellular ascorbate by ascorbate oxidase or ferricyanide enhanced apparent ascorbate efflux, suggesting that efflux of the vitamin was countered in part by its re-uptake on ascorbate transporters. Although basal ascorbate efflux was not calcium-dependent, increased entry of calcium into the cells enhanced ascorbate release. These results support the hypothesis that ascorbate efflux reflects trans-endothelial cell ascorbate movement out of the blood vessel.

Octanoic acid confers to royal jelly varroa-repellent properties

NASA Astrophysics Data System (ADS)

Nazzi, Francesco; Bortolomeazzi, Renzo; Della Vedova, Giorgio; Del Piccolo, Fabio; Annoscia, Desiderato; Milani, Norberto

2009-02-01

The mite Varroa destructor Anderson & Trueman is a parasite of the honeybee Apis mellifera L. and represents a major threat for apiculture in the Western world. Reproduction takes place only inside bee brood cells that are invaded just before sealing; drone cells are preferred over worker cells, whereas queen cells are not normally invaded. Lower incidence of mites in queen cells is at least partly due to the deterrent activity of royal jelly. In this study, the repellent properties of royal jelly were investigated using a lab bioassay. Chemical analysis showed that octanoic acid is a major volatile component of royal jelly; by contrast, the concentration is much lower in drone and worker larval food. Bioassays, carried out under lab conditions, demonstrated that octanoic acid is repellent to the mite. Field studies in bee colonies confirmed that the compound may interfere with the process of cell invasion by the mite.

Cell disruption for microalgae biorefineries.

PubMed

Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

2015-01-01

Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets.

PubMed

Chen, Jiao; Weihs, Daphne; Vermolen, Fred J

2018-04-01

Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler-Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration.

Electromagnetic cellular interactions.

PubMed

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Sheffield RNAi Screening Facility (SRSF): portfolio growth and technology development.

PubMed

Brown, Stephen

2014-05-01

The Sheffield RNAi Screening Facility (SRSF) (www.rnai.group.shef.ac.uk) was established in 2008 with Wellcome Trust and University of Sheffield funding, with the task to provide the first UK RNAi screening resource for academic groups interested in identifying genes required in a diverse range of biological processes using Drosophila cell culture. The SRSF has carried out a wide range of screens varying in sizes from bespoke small-scale libraries, targeting a few hundred genes, to high-throughput, genome-wide studies. The SRSF has grown and improved with a dedicated partnership of its academic customers based mainly in the UK. We are part of the UK Academics Functional Genomics Network, participating in organizing an annual meeting in London and are part of the University of Sheffield's D3N (www.d3n.org.uk), connecting academics, biotech and pharmaceutical companies with a multidisciplinary network in Drug Discovery and Development. Recently, the SRSF has been funded by the Yorkshire Cancer Research Fund to perform genome-wide RNAi screens using human cells as part of a core facility for regional Yorkshire Universities and screens are now underway. Overall the SRSF has carried out more than 40 screens from Drosophila and human cell culture experiments.

Construction of human induced pluripotent stem cell-derived oriented bone matrix microstructure by using in vitro engineered anisotropic culture model.

PubMed

Ozasa, Ryosuke; Matsugaki, Aira; Isobe, Yoshihiro; Saku, Taro; Yun, Hui-Suk; Nakano, Takayoshi

2018-02-01

Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold. The oriented collagen scaffold allowed hiPSCs-derived osteoblast alignment and further construction of anisotropic bone matrix which mimics the bone tissue microstructure. To the best of our knowledge, this is the first report showing the construction of bone mimetic anisotropic bone matrix microstructure from hiPSCs. Moreover, we demonstrated for the first time that the hiPSCs-derived osteoblasts possess a high level of intact functionality to regulate cell alignment. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 360-369, 2018. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

Suppression of lethal autoimmunity by regulatory T cells with a single TCR specificity

PubMed Central

Hemmers, Saskia; Schizas, Michail; Faire, Mehlika B.; Konopacki, Catherine; Schmidt-Supprian, Marc; Germain, Ronald N.

2017-01-01

The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity. An induced switch of the T reg cell TCR repertoire to a random repertoire also preserved, albeit to a limited degree, the ability to suppress lymphadenopathy and T helper cell type 2 activation. At the same time, these perturbations of the T reg cell TCR repertoire led to marked immune cell activation, tissue inflammation, and an ultimately severe autoimmunity, indicating the importance of diversity and specificity for optimal T reg cell function. PMID:28130403

Endosomal sorting complexes required for ESCRTing cells toward death during neurogenesis, neurodevelopment and neurodegeneration.

PubMed

Kaul, Zenia; Chakrabarti, Oishee

2018-03-25

The endosomal sorting complexes required for transport (ESCRT) proteins help in the recognition, sorting and degradation of ubiquitinated cargoes from the cell surface, long-lived proteins or aggregates, and aged organelles present in the cytosol. These proteins take part in the endo-lysosomal system of degradation. The ESCRT proteins also play an integral role in cytokinesis, viral budding and mRNA transport. Many neurodegenerative diseases are caused by toxic accumulation of cargo in the cell, which causes stress and ultimately leads to neuronal death. This accumulation of cargo occurs because of defects in the endo-lysosomal degradative pathway-loss of function of ESCRTs has been implicated in this mechanism. ESCRTs also take part in many survival processes, lack of which can culminate in neuronal cell death. While the role played by the ESCRT proteins in maintaining healthy neurons is known, their role in neurodegenerative diseases is still poorly understood. In this review, we highlight the importance of ESCRTs in maintaining healthy neurons and then suggest how perturbations in many of the survival mechanisms governed by these proteins could eventually lead to cell death; quite often these correlations are not so obviously laid out. Extensive neuronal death eventually culminates in neurodegeneration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

PubMed

Ahir, Bhavesh K; Pratten, Margaret K

2014-01-01

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

Study of melanoma invasion by FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

2008-02-01

Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

Summer Research Paper

NASA Technical Reports Server (NTRS)

Patel, Zarana

2011-01-01

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Three-dimensional structure and function of the Paramecium bursaria chlorella virus capsid.

PubMed

Zhang, Xinzheng; Xiang, Ye; Dunigan, David D; Klose, Thomas; Chipman, Paul R; Van Etten, James L; Rossmann, Michael G

2011-09-06

A cryoelectron microscopy 8.5 Å resolution map of the 1,900 Å diameter, icosahedral, internally enveloped Paramecium bursaria chlorella virus was used to interpret structures of the virus at initial stages of cell infection. A fivefold averaged map demonstrated that two minor capsid proteins involved in stabilizing the capsid are missing in the vicinity of the unique vertex. Reconstruction of the virus in the presence of host chlorella cell walls established that the spike at the unique vertex initiates binding to the cell wall, which results in the enveloped nucleocapsid moving closer to the cell. This process is concurrent with the release of the internal viral membrane that was linked to the capsid by many copies of a viral membrane protein in the mature infectous virus. Simultaneously, part of the trisymmetrons around the unique vertex disassemble, probably in part because two minor capsid proteins are absent, causing Paramecium bursaria chlorella virus and the cellular contents to merge, possibly as a result of enzyme(s) within the spike assembly. This may be one of only a few recordings of successive stages of a virus while infecting a eukaryotic host in pseudoatomic detail in three dimensions.

Three-dimensional structure and function of the Paramecium bursaria chlorella virus capsid

PubMed Central

Zhang, Xinzheng; Xiang, Ye; Dunigan, David D.; Klose, Thomas; Chipman, Paul R.; Van Etten, James L.; Rossmann, Michael G.

2011-01-01

A cryoelectron microscopy 8.5 Å resolution map of the 1,900 Å diameter, icosahedral, internally enveloped Paramecium bursaria chlorella virus was used to interpret structures of the virus at initial stages of cell infection. A fivefold averaged map demonstrated that two minor capsid proteins involved in stabilizing the capsid are missing in the vicinity of the unique vertex. Reconstruction of the virus in the presence of host chlorella cell walls established that the spike at the unique vertex initiates binding to the cell wall, which results in the enveloped nucleocapsid moving closer to the cell. This process is concurrent with the release of the internal viral membrane that was linked to the capsid by many copies of a viral membrane protein in the mature infectous virus. Simultaneously, part of the trisymmetrons around the unique vertex disassemble, probably in part because two minor capsid proteins are absent, causing Paramecium bursaria chlorella virus and the cellular contents to merge, possibly as a result of enzyme(s) within the spike assembly. This may be one of only a few recordings of successive stages of a virus while infecting a eukaryotic host in pseudoatomic detail in three dimensions. PMID:21873222

Characterization of p75{sup +} ectomesenchymal stem cells from rat embryonic facial process tissue

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

Wen, Xiujie; Liu, Luchuan; Deng, Manjing

2012-10-12

Highlights: Black-Right-Pointing-Pointer Ectomesenchymal stem cells (EMSCs) were found to migrate to rat facial processes at E11.5. Black-Right-Pointing-Pointer We successfully sorted p75NTR positive EMSCs (p75{sup +} EMSCs). Black-Right-Pointing-Pointer p75{sup +} EMSCs up to nine passages showed relative stable proliferative activity. Black-Right-Pointing-Pointer We examined the in vitro multilineage potential of p75{sup +} EMSCs. Black-Right-Pointing-Pointer p75{sup +}EMSCs provide an in vitro model for tooth morphogenesis. -- Abstract: Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well.more » However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial-mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75{sup +} EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75{sup +} EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering.« less

Crescentic Glomerulonephritis in a Polar Bear (Ursus maritimus)

PubMed Central

BABA, Hiroshi; KUDO, Tomoo; MAKINO, Yoshinori; MOCHIZUKI, Yasumasa; TAKAGI, Takayo; UNE, Yumi

2013-01-01

ABSTRACT Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman’s capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits. PMID:23856758

Crescentic glomerulonephritis in a polar bear (Ursus maritimus).

PubMed

Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi

2013-11-01

Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits.

Interferon-inducible effector mechanisms in cell-autonomous immunity

PubMed Central

MacMicking, John D.

2014-01-01

Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world. PMID:22531325

Extraction of Carbon Dioxide and Hydrogen from Seawater by an Electrochemical Acidification Cell. Part 4. Electrode Compartments of Cell Modified and Tested in Scaled-Up Mobile Unit

DTIC Science & Technology

2013-09-03

Electrochemical Acidification Cell Part IV: Electrode Compartments of Cell Modified and Tested in Scaled-Up Mobile Unit September 3, 2013 Approved for public...OF ABSTRACT Extraction of Carbon Dioxide and Hydrogen from Seawater by an Electrochemical Acidification Cell Part IV: Electrode Compartments of Cell...Electrochemical acidification cell Carbon dioxide Hydrogen Polarity reversal An electrochemical acidification cell was scaled-up and integrated into a

Role of Angiogenesis in Endodontics: Contributions of Stem Cells and Proangiogenic and Antiangiogenic Factors to Dental Pulp Regeneration

PubMed Central

Saghiri, Mohammad Ali; Asatourian, Armen; Sorenson, Christine M.; Sheibani, Nader

2016-01-01

Introduction Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. Methods A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Results Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Conclusions Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation. PMID:25649306

Immunohistochemical localization of the NH(2)-terminal and COOH-terminal fragments of dentin sialoprotein in mouse teeth.

PubMed

Yuan, Guohua; Yang, Guobin; Song, Guangtai; Chen, Zhi; Chen, Shuo

2012-08-01

Dentin sialoprotein (DSP) is a major non-collagenous protein in dentin. Mutation studies in human, along with gene knockout and transgenic experiments in mice, have confirmed the critical role of DSP for dentin formation. Our previous study reported that DSP is processed into fragments in mouse odontoblast-like cells. In order to gain insights into the function of DSP fragments, we further evaluated the expression pattern of DSP in the mouse odontoblast-like cells using immunohistochemistry and western blot assay with antibodies against the NH(2)-terminal and COOH-terminal regions of DSP. Then, the distribution profiles of the DSP NH(2)-terminal and COOH-terminal fragments and osteopontin (OPN) were investigated in mouse teeth at different ages by immunohistochemistry. In the odontoblast-like cells, multiple low molecular weight DSP fragments were detected, suggesting that part of the DSP protein was processed in the odontoblast-like cells. In mouse first lower molars, immunoreactions for anti-DSP-NH(2) antibody were intense in the predentin matrix but weak in mineralized dentin; in contrast, for anti-DSP-COOH antibody, strong immunoreactions were found in mineralized dentin, in particular dentinal tubules but weak in predentin. Therefore, DSP NH(2)-terminal and COOH-terminal fragments from odontoblasts were secreted to different parts of teeth, suggesting that they may play distinct roles in dentinogenesis. Meanwhile, both DSP antibodies showed weak staining in reactionary dentin (RD), whereas osteopontin (OPN) was clearly positive in RD. Therefore, DSP may be less crucial for RD formation than OPN.

Immunohistochemical localization of the NH2-terminal and COOH-terminal fragments of dentin sialoprotein in mouse teeth

PubMed Central

Yuan, Guohua; Yang, Guobin; Song, Guangtai

2013-01-01

Dentin sialoprotein (DSP) is a major non-collagenous protein in dentin. Mutation studies in human, along with gene knockout and transgenic experiments in mice, have confirmed the critical role of DSP for dentin formation. Our previous study reported that DSP is processed into fragments in mouse odontoblast-like cells. In order to gain insights into the function of DSP fragments, we further evaluated the expression pattern of DSP in the mouse odontoblast-like cells using immunohistochemistry and western blot assay with antibodies against the NH2-terminal and COOH-terminal regions of DSP. Then, the distribution profiles of the DSP NH2-terminal and COOH-terminal fragments and osteopontin (OPN) were investigated in mouse teeth at different ages by immunohistochemistry. In the odontoblast-like cells, multiple low molecular weight DSP fragments were detected, suggesting that part of the DSP protein was processed in the odontoblast-like cells. In mouse first lower molars, immunoreactions for anti-DSP-NH2 antibody were intense in the predentin matrix but weak in mineralized dentin; in contrast, for anti-DSP-COOH antibody, strong immunoreactions were found in mineralized dentin, in particular dentinal tubules but weak in predentin. Therefore, DSP NH2-terminal and COOH-terminal fragments from odontoblasts were secreted to different parts of teeth, suggesting that they may play distinct roles in dentinogenesis. Meanwhile, both DSP antibodies showed weak staining in reactionary dentin (RD), whereas osteopontin (OPN) was clearly positive in RD. Therefore, DSP may be less crucial for RD formation than OPN. PMID:22581382

Novel processing of iron-manganese alloy-based biomaterials by inkjet 3-D printing.

PubMed

Chou, Da-Tren; Wells, Derrick; Hong, Daeho; Lee, Boeun; Kuhn, Howard; Kumta, Prashant N

2013-11-01

The present work provides an assessment of 3-D printed iron-manganese biodegradable scaffolds as a bone scaffold material. Iron-based alloys have been investigated due to their high strength and ability to slowly corrode. Current fabrications of Fe-based materials generate raw material which must be machined into their desired form. By using inkjet 3-D printing, a technique which generates complex, customizable parts from powders mechanically milled Fe-30Mn (wt.%) powder was directly processed into scaffolds. The 3-D printed parts maintained an open porosity of 36.3% and formed a mixed phase alloy of martensitic ε and austenitic γ phases. Electrochemical corrosion tests showed the 3-D printed Fe-Mn to desirably corrode significantly more rapidly than pure iron. The scaffolds exhibited similar tensile mechanical properties to natural bone, which may reduce the risk of stress shielding. Cell viability testing of MC3T3-E1 pre-osteoblast cells seeded directly onto the Fe-Mn scaffolds using the live/dead assay and with cells cultured in the presence of the scaffolds' degradation products demonstrated good in vitro cytocompatibility compared to tissue culture plastic. Cell infiltration into the open pores of the 3-D printed scaffolds was also observed. Based on this preliminary study, we believe that 3-D printed Fe-Mn alloy is a promising material for craniofacial biomaterial applications, and represents an opportunity for other biodegradable metals to be fabricated using this unique method. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modulation of host cell biology by plant pathogenic microbes.

PubMed

Le Fevre, Ruth; Evangelisti, Edouard; Rey, Thomas; Schornack, Sebastian

2015-01-01

Plant-pathogen interactions can result in dramatic visual changes in the host, such as galls, phyllody, pseudoflowers, and altered root-system architecture, indicating that the invading microbe has perturbed normal plant growth and development. These effects occur on a cellular level but range up to the organ scale, and they commonly involve attenuation of hormone homeostasis and deployment of effector proteins with varying activities to modify host cell processes. This review focuses on the cellular-reprogramming mechanisms of filamentous and bacterial plant pathogens that exhibit a biotrophic lifestyle for part, if not all, of their lifecycle in association with the host. We also highlight strategies for exploiting our growing knowledge of microbial host reprogramming to study plant processes other than immunity and to explore alternative strategies for durable plant resistance.

Employing epigenetics to augment the expression of therapeutic proteins in mammalian cells.

PubMed

Kwaks, Ted H J; Otte, Arie P

2006-03-01

Recombinant proteins form an increasingly large part of the portfolio of biopharmaceutical companies. Production of these often complex transgenic proteins is achieved predominantly in mammalian cell lines but the process is hampered by low yields and unstable expression. Some of these problems are caused by gene silencing at the level of chromatin - so-called epigenetic gene silencing. Here, we describe approaches, which have emerged during the past few years, designed to interfere with epigenetic gene silencing with the aim of enhancing and stabilizing transgene expression. These include targeting histones, the inclusion of specific DNA elements and targeting sites of high gene-expression. We conclude that employing epigenetic gene regulation tools, in combination with further process optimization, might represent the next step forward in the production of therapeutic proteins.

Modelling emergence of oscillations in communicating bacteria: a structured approach from one to many cells

PubMed Central

Mina, Petros; di Bernardo, Mario; Savery, Nigel J.; Tsaneva-Atanasova, Krasimira

2013-01-01

Population-level measurements of phenotypic behaviour in biological systems may not necessarily reflect individual cell behaviour. To assess qualitative changes in the behaviour of a single cell, when alone and when part of a community, we developed an agent-based model describing the metabolic states of a population of quorum-coupled cells. The modelling is motivated by published experimental work of a synthetic genetic regulatory network (GRN) used in Escherichia coli cells that exhibit oscillatory behaviour across the population. To decipher the mechanisms underlying oscillations in the system, we investigate the behaviour of the model via numerical simulation and bifurcation analysis. In particular, we study the effect of an increase in population size as well as the spatio-temporal behaviour of the model. Our results demonstrate that oscillations are possible only in the presence of a high concentration of the coupling chemical and are due to a time scale separation in key regulatory components of the system. The model suggests that the population establishes oscillatory behaviour as the system's preferred stable state. This is achieved via an effective increase in coupling across the population. We conclude that population effects in GRN design need to be taken into consideration and be part of the design process. This is important in planning intervention strategies or designing specific cell behaviours. PMID:23135248

Modelling emergence of oscillations in communicating bacteria: a structured approach from one to many cells.

PubMed

Mina, Petros; di Bernardo, Mario; Savery, Nigel J; Tsaneva-Atanasova, Krasimira

2013-01-06

Population-level measurements of phenotypic behaviour in biological systems may not necessarily reflect individual cell behaviour. To assess qualitative changes in the behaviour of a single cell, when alone and when part of a community, we developed an agent-based model describing the metabolic states of a population of quorum-coupled cells. The modelling is motivated by published experimental work of a synthetic genetic regulatory network (GRN) used in Escherichia coli cells that exhibit oscillatory behaviour across the population. To decipher the mechanisms underlying oscillations in the system, we investigate the behaviour of the model via numerical simulation and bifurcation analysis. In particular, we study the effect of an increase in population size as well as the spatio-temporal behaviour of the model. Our results demonstrate that oscillations are possible only in the presence of a high concentration of the coupling chemical and are due to a time scale separation in key regulatory components of the system. The model suggests that the population establishes oscillatory behaviour as the system's preferred stable state. This is achieved via an effective increase in coupling across the population. We conclude that population effects in GRN design need to be taken into consideration and be part of the design process. This is important in planning intervention strategies or designing specific cell behaviours.

Intercellular transfer along the trichomes of the invasive terminal heterocyst forming cyanobacterium Cylindrospermopsis raciborskii CS-505.

PubMed

Plominsky, Álvaro M; Delherbe, Nathalie; Mandakovic, Dinka; Riquelme, Brenda; González, Karen; Bergman, Birgitta; Mariscal, Vicente; Vásquez, Mónica

2015-03-01

Cylindrospermopsis raciborskii CS-505 is an invasive freshwater filamentous cyanobacterium that when grown diazotrophically may develop trichomes of up to 100 vegetative cells while differentiating only two end heterocysts, the sole sites for their N2-fixation process. We examined the diazotrophic growth and intercellular transfer mechanisms in C. raciborskii CS-505. Subjecting cultures to a combined-nitrogen-free medium to elicit N2 fixation, the trichome length remained unaffected while growth rates decreased. The structures and proteins for intercellular communication showed that while a continuous periplasmic space was apparent along the trichomes, the putative septal junction sepJ gene is divided into two open reading frames and lacks several transmembrane domains unlike the situation in Anabaena, differentiating a 5-fold higher frequency of heterocysts. FRAP analyses also showed that the dyes calcein and 5-CFDA were taken up by heterocysts and vegetative cells, and that the transfer from heterocysts and 'terminal' vegetative cells showed considerably higher transfer rates than that from vegetative cells located in the middle of the trichomes. The data suggest that C. raciborskii CS-505 compensates its low-frequency heterocyst phenotype by a highly efficient transfer of the fixed nitrogen towards cells in distal parts of the trichomes (growing rapidly) while cells in central parts suffers (slow growth). © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Circulating membrane-derived microvesicles in redox biology.

PubMed

Larson, Michael Craig; Hillery, Cheryl A; Hogg, Neil

2014-08-01

Microparticles or microvesicles (MVs) are subcellular membrane blebs shed from all cells in response to various stimuli. MVs carry a battery of signaling molecules, many of them related to redox-regulated processes. The role of MVs, either as a cause or as a result of cellular redox signaling, has been increasingly recognized over the past decade. This is in part due to advances in flow cytometry and its detection of MVs. Notably, recent studies have shown that circulating MVs from platelets and endothelial cells drive reactive species-dependent angiogenesis; circulating MVs in cancer alter the microenvironment and enhance invasion through horizontal transfer of mutated proteins and nucleic acids and harbor redox-regulated matrix metalloproteinases and procoagulative surface molecules; and circulating MVs from red blood cells and other cells modulate cell-cell interactions through scavenging or production of nitric oxide and other free radicals. Although our recognition of MVs in redox-related processes is growing, especially in the vascular biology field, much remains unknown regarding the various biologic and pathologic functions of MVs. Like reactive oxygen and nitrogen species, MVs were originally believed to have a solely pathological role in biology. And like our understanding of reactive species, it is now clear that MVs also play an important role in normal growth, development, and homeostasis. We are just beginning to understand how MVs are involved in various biological processes-developmental, homeostatic, and pathological-and the role of MVs in redox signaling is a rich and exciting area of investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Flat-plate solar array project. Volume 2: Silicon material

NASA Technical Reports Server (NTRS)

Lutwack, R.

1986-01-01

The goal of the Silicon Material Task, a part of the Flat Plate Solar Array (FSA) Project, was to develop and demonstate the technology for the low cost production of silicon of suitable purity to be used as the basic material for the manufacture of terrestrial photovoltaic solar cells. Summarized are 11 different processes for the production of silicon that were investigated and developed to varying extent by industrial, university, and Government researchers. The silane production section of the Union Carbide Corp. (UCC) silane process was developed completely in this program. Coupled with Siemens-type chemical vapor deposition reactors, the process was carried through the pilot stage. The overall UCC process involves the conversion of metallurgical-grade silicon to silane followed by decomposition of the silane to purified silicon. The other process developments are described to varying extents. Studies are reported on the effects of impurities in silicon on both silicon-material properties and on solar cell performance. These studies on the effects of impurities yielded extensive information and models for relating specific elemental concentrations to levels of deleterious effects.

Flat-plate solar array project. Volume 2: Silicon material

NASA Astrophysics Data System (ADS)

Lutwack, R.

1986-10-01

The goal of the Silicon Material Task, a part of the Flat Plate Solar Array (FSA) Project, was to develop and demonstate the technology for the low cost production of silicon of suitable purity to be used as the basic material for the manufacture of terrestrial photovoltaic solar cells. Summarized are 11 different processes for the production of silicon that were investigated and developed to varying extent by industrial, university, and Government researchers. The silane production section of the Union Carbide Corp. (UCC) silane process was developed completely in this program. Coupled with Siemens-type chemical vapor deposition reactors, the process was carried through the pilot stage. The overall UCC process involves the conversion of metallurgical-grade silicon to silane followed by decomposition of the silane to purified silicon. The other process developments are described to varying extents. Studies are reported on the effects of impurities in silicon on both silicon-material properties and on solar cell performance. These studies on the effects of impurities yielded extensive information and models for relating specific elemental concentrations to levels of deleterious effects.

The role of plant processing for the cancer preventive potential of Ethiopian kale (Brassica carinata)

PubMed Central

Odongo, Grace Akinyi; Schlotz, Nina; Herz, Corinna; Hanschen, Franziska S.; Baldermann, Susanne; Neugart, Susanne; Trierweiler, Bernhard; Frommherz, Lara; Franz, Charles M. A. P.; Ngwene, Benard; Luvonga, Abraham Wahid; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

2017-01-01

ABSTRACT Background: Ethiopian kale (Brassica carinata) is a horticulturally important crop used as leafy vegetable in large parts of East and Southern Africa. The leaves are reported to contain high concentrations of health-promoting secondary plant metabolites. However, scientific knowledge on their health benefits is scarce. Objective: This study aimed to determine the cancer preventive potential of B. carinata using a human liver in vitro model focusing on processing effects on the pattern of secondary plant metabolites and bioactivity. Design: B. carinata was cultivated under controlled conditions and differentially processed (raw, fermented, or cooked) after harvesting. Human liver cancer cells (HepG2) were treated with ethanolic extracts of raw or processed B. carinata leaves and analyzed for their anti-genotoxic, anti-oxidant, and cytostatic potential. Chemical analyses were carried out on glucosinolates including breakdown products, phenolic compounds, carotenoids, and chlorophyll content. Results: Pre-treatment with B. carinata extracts concentration dependently reduced aflatoxin-induced DNA damage in the Comet assay, reduced the production of reactive oxygen species as determined by electron paramagnetic resonance spectroscopy, and induced Nrf2-mediated gene expression. Increasing extract concentrations also promoted cytostasis. Processing had a significant effect on the content of secondary plant metabolites. However, different processing methodologies did not dramatically decrease bioactivity, but enhanced the protective effect in some of the endpoints studied. Conclusion: Our findings highlight the cancer preventive potential of B. carinata as indicated by the protection of human liver cells against aflatoxin in vitro. In general, consumption of B. carinata should be encouraged as part of chemopreventive measures to combat prevalence of aflatoxin-induced diseases. PMID:28326001

Cytotopographical specialization of enzymatically isolated rabbit retinal Müller (glial) cells: K+ conductivity of the cell membrane.

PubMed

Reichenbach, A; Eberhardt, W

1988-01-01

Müller (radial glial) cells were isolated from rabbit retinae by means of papaine and mechanical dissociation. Regional membrane properties of these cells were studied by intracellular microelectrode recordings of potential responses to local application of high K+ solutions. When different parts of the cell membrane were exposed to high K+, the amplitude of the depolarizing responses varied greatly, indicating a strong regional specialization of the membrane properties. Using morphometrical data of isolated rabbit Müller cells, and a simple circuit model, we calculated the endfoot membrane to constitute more than 80% of the total K+ conductance of the cell; the specific resistivity of the endfoot membrane was about 400 omega cm2, i.e., more than 40 times less than that of the membrane of the vitread process, which is immediately adjacent. This kind of regional membrane specialization seems to be optimized in respect to the Müller cells' ability to carry spatial buffering K+ currents.

Bisphenol A exposure leads to specific microRNA alterations in placental cells.

PubMed

Avissar-Whiting, Michele; Veiga, Keila R; Uhl, Kristen M; Maccani, Matthew A; Gagne, Luc A; Moen, Erika L; Marsit, Carmen J

2010-07-01

Exposure to bisphenol A (BPA) has been observed to alter developmental pathways and cell processes, at least in part, through epigenetic mechanisms. This study sought to investigate the effect of BPA on microRNAs (miRNAs) in human placental cells. miRNA microarray was performed following BPA treatment in three immortalized cytotrophoblast cell lines and the results validated using quantitative real-time PCR. For functional analysis, overexpression constructs were stably transfected into cells that were then assayed for changes in proliferation and response to toxicants. Microarray analysis revealed several miRNAs to be significantly altered in response to BPA treatment in two cell lines. Real-time PCR results confirmed that miR-146a was particularly strongly induced and its overexpression in cells led to slower proliferation as well as higher sensitivity to the DNA damaging agent, bleomycin. Overall, these results suggest that BPA can alter miRNA expression in placental cells, a potentially novel mode of BPA toxicity.

Bisphenol A Exposure Leads to Specific MicroRNA Alterations in Placental Cells

PubMed Central

Avissar-Whiting, Michele; Veiga, Keila; Uhl, Kristen; Maccani, Matthew; Gagne, Luc; Moen, Erika; Marsit, Carmen J.

2010-01-01

Exposure to bisphenol-A (BPA) has been observed to alter developmental pathways and cell processes, at least in part, through epigenetic mechanisms. This study sought to investigate the effect of BPA on microRNAs (miRNAs) in human placental cells. miRNA microarray was performed following BPA treatment in three immortalized cytotrophoblast cell lines and the results validated using quantitative real-time PCR. For functional analysis, overexpression constructs were stably transfected into cells that were then assayed for changes in proliferation and response to toxicants. Microarray analysis revealed several miRNAs to be significantly altered in response to BPA treatment in two cell lines. Real-time PCR results confirmed that miR-146a was particularly strongly induced and its overexpression in cells led to slower proliferation as well as higher sensitivity to the DNA damaging agent, bleomycin. Overall, these results suggest that BPA can alter miRNA expression in placental cells, a potentially novel mode of BPA toxicity. PMID:20417706

Systems modelling methodology for the analysis of apoptosis signal transduction and cell death decisions.

PubMed

Rehm, Markus; Prehn, Jochen H M

2013-06-01

Systems biology and systems medicine, i.e. the application of systems biology in a clinical context, is becoming of increasing importance in biology, drug discovery and health care. Systems biology incorporates knowledge and methods that are applied in mathematics, physics and engineering, but may not be part of classical training in biology. We here provide an introduction to basic concepts and methods relevant to the construction and application of systems models for apoptosis research. We present the key methods relevant to the representation of biochemical processes in signal transduction models, with a particular reference to apoptotic processes. We demonstrate how such models enable a quantitative and temporal analysis of changes in molecular entities in response to an apoptosis-inducing stimulus, and provide information on cell survival and cell death decisions. We introduce methods for analyzing the spatial propagation of cell death signals, and discuss the concepts of sensitivity analyses that enable a prediction of network responses to disturbances of single or multiple parameters. Copyright © 2013 Elsevier Inc. All rights reserved.

Phosphoproteomics profiling suggests a role for nuclear βΙPKC in transcription processes of undifferentiated murine embryonic stem cells.

PubMed

Costa-Junior, Helio Miranda; Garavello, Nicole Milaré; Duarte, Mariana Lemos; Berti, Denise Aparecida; Glaser, Talita; de Andrade, Alexander; Labate, Carlos A; Ferreira, André Teixeira da Silva; Perales, Jonas Enrique Aguilar; Xavier-Neto, José; Krieger, José Eduardo; Schechtman, Deborah

2010-12-03

Protein kinase C (PKC) plays a key role in embryonic stem cell (ESC) proliferation, self-renewal, and differentiation. However, the function of specific PKC isoenzymes have yet to be determined. Of the PKCs expressed in undifferentiated ESCs, βIPKC was the only isoenzyme abundantly expressed in the nuclei. To investigate the role of βΙPKC in these cells, we employed a phosphoproteomics strategy and used two classical (cPKC) peptide modulators and one βIPKC-specific inhibitor peptide. We identified 13 nuclear proteins that are direct or indirect βΙPKC substrates in undifferentiated ESCs. These proteins are known to be involved in regulating transcription, splicing, and chromatin remodeling during proliferation and differentiation. Inhibiting βΙPKC had no effect on DNA synthesis in undifferentiated ESCs. However, upon differentiation, many cells seized to express βΙPKC and βΙPKC was frequently found in the cytoplasm. Taken together, our results suggest that βIPKC takes part in the processes that maintain ESCs in their undifferentiated state.

Putting together the clues of the everlasting neuro-cardiac liaison.

PubMed

Franzoso, Mauro; Zaglia, Tania; Mongillo, Marco

2016-07-01

Starting from the late embryonic development, the sympathetic nervous system extensively innervates the heart and modulates its activity during the entire lifespan. The distribution of myocardial sympathetic processes is finely regulated by the secretion of limiting amounts of pro-survival neurotrophic factors by cardiac cells. Norepinephrine release by the neurons rapidly modulates myocardial electrophysiology, and increases the rate and force of cardiomyocyte contractions. Sympathetic processes establish direct interaction with cardiomyocytes, characterized by the presence of neurotransmitter vesicles and reduced cell-cell distance. Whether such contacts have a functional role in both neurotrophin- and catecholamine-dependent communication between the two cell types, is poorly understood. In this review we will address the effects of the sympathetic neuron activity on the myocardium and the hypothesis that the direct neuro-cardiac contact might have a key role both in norepinephrine and neurotrophin mediated signaling. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2016 Elsevier B.V. All rights reserved.

Breast cancer mitosis detection in histopathological images with spatial feature extraction

NASA Astrophysics Data System (ADS)

Albayrak, Abdülkadir; Bilgin, Gökhan

2013-12-01

In this work, cellular mitosis detection in histopathological images has been investigated. Mitosis detection is very expensive and time consuming process. Development of digital imaging in pathology has enabled reasonable and effective solution to this problem. Segmentation of digital images provides easier analysis of cell structures in histopathological data. To differentiate normal and mitotic cells in histopathological images, feature extraction step is very crucial step for the system accuracy. A mitotic cell has more distinctive textural dissimilarities than the other normal cells. Hence, it is important to incorporate spatial information in feature extraction or in post-processing steps. As a main part of this study, Haralick texture descriptor has been proposed with different spatial window sizes in RGB and La*b* color spaces. So, spatial dependencies of normal and mitotic cellular pixels can be evaluated within different pixel neighborhoods. Extracted features are compared with various sample sizes by Support Vector Machines using k-fold cross validation method. According to the represented results, it has been shown that separation accuracy on mitotic and non-mitotic cellular pixels gets better with the increasing size of spatial window.

Arming Technology in Yeast-Novel Strategy for Whole-cell Biocatalyst and Protein Engineering.

PubMed

Kuroda, Kouichi; Ueda, Mitsuyoshi

2013-09-09

Cell surface display of proteins/peptides, in contrast to the conventional intracellular expression, has many attractive features. This arming technology is especially effective when yeasts are used as a host, because eukaryotic modifications that are often required for functional use can be added to the surface-displayed proteins/peptides. A part of various cell wall or plasma membrane proteins can be genetically fused to the proteins/peptides of interest to be displayed. This technology, leading to the generation of so-called "arming technology", can be employed for basic and applied research purposes. In this article, we describe various strategies for the construction of arming yeasts, and outline the diverse applications of this technology to industrial processes such as biofuel and chemical productions, pollutant removal, and health-related processes, including oral vaccines. In addition, arming technology is suitable for protein engineering and directed evolution through high-throughput screening that is made possible by the feature that proteins/peptides displayed on cell surface can be directly analyzed using intact cells without concentration and purification. Actually, novel proteins/peptides with improved or developed functions have been created, and development of diagnostic/therapeutic antibodies are likely to benefit from this powerful approach.

PhEXPA1, a Petunia hybrida expansin, is involved in cell wall metabolism and in plant architecture specification.

PubMed

Dal Santo, Silvia; Fasoli, Marianna; Cavallini, Erika; Tornielli, Giovanni Battista; Pezzotti, Mario; Zenoni, Sara

2011-12-01

Expansins are wall-loosening proteins that induce wall stress relaxation and irreversible wall extension in a pH-dependent manner. Despite a substantial body of work has been performed on the characterization of many expansins genes in different plant species, the knowledge about their precise biological roles during plant development remains scarce. To yield insights into the expansion process in Petunia hybrida, PhEXPA1, an expansin gene preferentially expressed in petal limb, has been characterized. The constitutive overexpression of PhEXPA1 significantly increased expansin activity, cells size and organ dimensions. Moreover, 35S::PhEXPA1 transgenic plants exhibited an altered cell wall polymer composition and a precocious timing of axillary meristem development compared with wild-type plants. These findings supported a previous hypothesis that expansins are not merely structural proteins involved in plant cell wall metabolism but they also take part in many plant development processes. Here, to support this expansins dual role, we discuss about differential cell wall-related genes expressed in PhEXPA1 expression mutants and gradients of altered petunia branching pattern. © 2011 Landes Bioscience

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.

Expanding the universe of cytokines and pattern recognition receptors: galectins and glycans in innate immunity.

PubMed

Cerliani, Juan P; Stowell, Sean R; Mascanfroni, Iván D; Arthur, Connie M; Cummings, Richard D; Rabinovich, Gabriel A

2011-02-01

Effective immunity relies on the recognition of pathogens and tumors by innate immune cells through diverse pattern recognition receptors (PRRs) that lead to initiation of signaling processes and secretion of pro- and anti-inflammatory cytokines. Galectins, a family of endogenous lectins widely expressed in infected and neoplastic tissues have emerged as part of the portfolio of soluble mediators and pattern recognition receptors responsible for eliciting and controlling innate immunity. These highly conserved glycan-binding proteins can control immune cell processes through binding to specific glycan structures on pathogens and tumors or by acting intracellularly via modulation of selective signaling pathways. Recent findings demonstrate that various galectin family members influence the fate and physiology of different innate immune cells including polymorphonuclear neutrophils, mast cells, macrophages, and dendritic cells. Moreover, several pathogens may actually utilize galectins as a mechanism of host invasion. In this review, we aim to highlight and integrate recent discoveries that have led to our current understanding of the role of galectins in host-pathogen interactions and innate immunity. Challenges for the future will embrace the rational manipulation of galectin-glycan interactions to instruct and shape innate immunity during microbial infections, inflammation, and cancer.

Bovine somatic cell nuclear transfer.

PubMed

Ross, Pablo J; Cibelli, Jose B

2010-01-01

Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.

Effect of acetic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

PubMed

Xu, Jian; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

2014-09-01

An integrated citric acid-methane fermentation process was proposed to solve the problem of extraction wastewater in citric acid fermentation process. Extraction wastewater was treated by anaerobic digestion and then recycled for the next batch of citric acid fermentation to eliminate wastewater discharge and reduce water resource consumption. Acetic acid as an intermediate product of methane fermentation was present in anaerobic digestion effluent. In this study, the effect of acetic acid on citric acid fermentation was investigated and results showed that lower concentration of acetic acid could promote Aspergillus niger growth and citric acid production. 5-Cyano-2,3-ditolyl tetrazolium chloride (CTC) staining was used to quantify the activity of A. niger cells, and the results suggested that when acetic acid concentration was above 8 mM at initial pH 4.5, the morphology of A. niger became uneven and the part of the cells' activity was significantly reduced, thereby resulting in deceasing of citric acid production. Effects of acetic acid on citric acid fermentation, as influenced by initial pH and cell number in inocula, were also examined. The result indicated that inhibition by acetic acid increased as initial pH declined and was rarely influenced by cell number in inocula.

Characterization of cytochrome c as marker for retinal cell degeneration by uv/vis spectroscopic imaging

NASA Astrophysics Data System (ADS)

Hollmach, Julia; Schweizer, Julia; Steiner, Gerald; Knels, Lilla; Funk, Richard H. W.; Thalheim, Silko; Koch, Edmund

2011-07-01

Retinal diseases like age-related macular degeneration have become an important cause of visual loss depending on increasing life expectancy and lifestyle habits. Due to the fact that no satisfying treatment exists, early diagnosis and prevention are the only possibilities to stop the degeneration. The protein cytochrome c (cyt c) is a suitable marker for degeneration processes and apoptosis because it is a part of the respiratory chain and involved in the apoptotic pathway. The determination of the local distribution and oxidative state of cyt c in living cells allows the characterization of cell degeneration processes. Since cyt c exhibits characteristic absorption bands between 400 and 650 nm wavelength, uv/vis in situ spectroscopic imaging was used for its characterization in retinal ganglion cells. The large amount of data, consisting of spatial and spectral information, was processed by multivariate data analysis. The challenge consists in the identification of the molecular information of cyt c. Baseline correction, principle component analysis (PCA) and cluster analysis (CA) were performed in order to identify cyt c within the spectral dataset. The combination of PCA and CA reveals cyt c and its oxidative state. The results demonstrate that uv/vis spectroscopic imaging in conjunction with sophisticated multivariate methods is a suitable tool to characterize cyt c under in situ conditions.

Progress towards computer simulation of NiH2 battery performance over life

NASA Technical Reports Server (NTRS)

Zimmerman, Albert H.; Quinzio, M. V.

1995-01-01

The long-term performance of rechargeable battery cells has traditionally been verified through life-testing, a procedure that generally requires significant commitments of funding and test resources. In the situation of nickel hydrogen battery cells, which have the capability of providing extremely long cycle life, the time and cost required to conduct even accelerated testing has become a serious impediment to transitioning technology improvements into spacecraft applications. The utilization of computer simulations to indicate the changes in performance to be expected in response to design or operating changes in nickel hydrogen cells is therefore a particularly attractive tool in advanced battery development, as well as for verifying performance in different applications. Computer-based simulations of the long-term performance of rechargeable battery cells have typically had very limited success in the past. There are a number of reasons for the lack in progress in this area. First, and probably most important, all battery cells are relatively complex electrochemical systems, in which performance is dictated by a large number of interacting physical and chemical processes. While the complexity alone is a significant part of the problem, in many instances the fundamental chemical and physical processes underlying long-term degradation and its effects on performance have not even been understood. Second, while specific chemical and physical changes within cell components have been associated with degradation, there has been no generalized simulation architecture that enables the chemical and physical structure (and changes therein) to be translated into cell performance. For the nickel hydrogen battery cell, our knowledge of the underlying reactions that control the performance of this cell has progressed to where it clearly is possible to model them. The recent development of a relative generalized cell modelling approach provides the framework for translating the chemical and physical structure of the components inside a cell into its performance characteristics over its entire cycle life. This report describes our approach to this task in terms of defining those processes deemed critical in controlling performance over life, and the model architecture required to translate the fundamental cell processes into performance profiles.

Methods in Molecular Biology: Germline Stem Cells | Center for Cancer Research

Cancer.gov

The protocols in Germline Stem Cells are intended to present selected genetic, molecular, and cellular techniques used in germline stem cell research. The book is divided into two parts. Part I covers germline stem cell identification and regulation in model organisms. Part II covers current techniques used in in vitro culture and applications of germline stem cells.

Engineering a Grid-Tied Residential Photovoltaic System: A Student Activity

ERIC Educational Resources Information Center

Litowitz, Len S.

2012-01-01

Photovoltaics is a term that refers to thin cells that have the ability to directly convert sunlight into electricity. This process occurs without the use of any moving parts, and the sunlight is free for the taking if it can be captured for useful purposes like heating water or air or producing electricity. As the cost of installing a…

BRAIN REGENERATION IN PHYSIOLOGY AND PATHOLOGY: THE IMMUNE SIGNATURE DRIVING THERAPEUTIC PLASTICITY OF NEURAL STEM CELLS

PubMed Central

Martino, Gianvito; Pluchino, Stefano; Bonfanti, Luca; Schwartz, Michal

2013-01-01

Regenerative processes occurring under physiological (maintenance) and pathological (reparative) conditions are a fundamental part of life and vary greatly among different species, individuals, and tissues. Physiological regeneration occurs naturally as a consequence of normal cell erosion, or as an inevitable outcome of any biological process aiming at the restoration of homeostasis. Reparative regeneration occurs as a consequence of tissue damage. Although the central nervous system (CNS) has been considered for years as a “perennial” tissue, it has recently become clear that both physiological and reparative regeneration occur also within the CNS to sustain tissue homeostasis and repair. Proliferation and differentiation of neural stem/progenitor cells (NPCs) residing within the healthy CNS, or surviving injury, are considered crucial in sustaining these processes. Thus a large number of experimental stem cell-based transplantation systems for CNS repair have recently been established. The results suggest that transplanted NPCs promote tissue repair not only via cell replacement but also through their local contribution to changes in the diseased tissue milieu. This review focuses on the remarkable plasticity of endogenous and exogenous (transplanted) NPCs in promoting repair. Special attention will be given to the cross-talk existing between NPCs and CNS-resident microglia as well as CNS-infiltrating immune cells from the circulation, as a crucial event sustaining NPC-mediated neuroprotection. Finally, we will propose the concept of the context-dependent potency of transplanted NPCs (therapeutic plasticity) to exert multiple therapeutic actions, such as cell replacement, neurotrophic support, and immunomodulation, in CNS repair. PMID:22013212

Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair.

PubMed

Khosla, Sundeep; Westendorf, Jennifer J; Mödder, Ulrike I

2010-12-01

There is growing interest in the use of mesenchymal stem cells for bone repair. As a major reason for normal bone remodeling is the removal of fatigue microcracks, advances in our understanding of this process may inform approaches to enhance fracture healing. Increasing evidence now indicates that physiological bone remodeling occurs in close proximity to blood vessels and that these vessels carry perivascular stem cells that differentiate into osteoblasts. Similarly, fracture healing is critically dependent on the ingrowth of blood vessels not only for a nutrient supply but also for the influx of osteoblasts. A number of animal and human studies have now shown the potential benefit of bone marrow-derived mesenchymal stem cells in enhancing bone repair. However, as in other tissues, the question of whether these cells improve fracture healing directly by differentiating into osteoblasts or indirectly by secreting paracrine factors that recruit blood vessels and the accompanying perivascular stem cells remains a major unresolved issue. Moreover, CD34+ cells, which are enriched for endothelial/hematopoietic cells, have also shown efficacy in various bone repair models, at least in part due to the induction of angiogenesis and recruitment of host progenitor cells. Thus, mesenchymal and nonmesenchymal stem/progenitor cells are attractive options for bone repair. It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process.

Effects of antitopoisomerase drugs on chromosome recombinations and segregation in grasshopper

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

Palitti, F.; Motta, S.; Grazioso, C.

1993-12-31

The role of different cellular functions which are required for the production of euploid cells can be studied through the use of mutants that are defective in the control of both the meiotic and mitotic cell cycle or through the use of compounds which interface with the various cellular targets which have a role in the segregation of chromosomes. The role of the achromatic part of the mitotic apparatus in the production of aneuploidy is well recognized. Substantial progress has been made in understanding the role of the chromatic part, for example, there are observations that disturbances in the normalmore » {open_quotes}metabolism{close_quotes} of the chromosomes (i.e. chromosome condensation, defective DNA repair or recombination) can affect chromosome segregation. Between the processes of both meiosis and mitosis that lead to nuclear division there are, however, important differences.« less

Regulatory Peptides in Plants.

PubMed

Vanyushin, B F; Ashapkin, V V; Aleksandrushkina, N I

2017-02-01

Many different peptides regulating cell differentiation, growth, and development are found in plants. Peptides participate in regulation of plant ontogenesis starting from pollination, pollen tube growth, and the very early stages of embryogenesis, including formation of embryo and endosperm. They direct differentiation of meristematic stem cells, formation of tissues and individual organs, take part in regulation of aging, fruit maturation, and abscission of plant parts associated with apoptosis. Biological activity of peptides is observed at very low concentrations, and it has mainly signal nature and hormonal character. "Mature" peptides appear mainly due to processing of protein precursors with (or without) additional enzymatic modifications. Plant peptides differ in origin, structure, and functional properties. Their specific action is due to binding with respective receptors and interactions with various proteins and other factors. Peptides can also regulate physiological functions by direct peptide-protein interactions. Peptide action is coordinated with the action of known phytohormones (auxins, cytokinins, and others); thus, peptides control phytohormonal signal pathways.

Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System

PubMed Central

Nieto-Sampedro, Manuel; Valle-Argos, Beatriz; Gómez-Nicola, Diego; Fernández-Mayoralas, Alfonso; Nieto-Díaz, Manuel

2011-01-01

Treated glioblastoma patients survive from 6 to 14 months. In the first part of this review, we describe glioma origins, cancer stem cells and the genomic alterations that generate dysregulated cell division, with enhanced proliferation and diverse response to radiation and chemotherapy. We review the pathways that mediate tumour cell proliferation, neo-angiogenesis, tumor cell invasion, as well as necrotic and apoptotic cell death. Then, we examine the ability of gliomas to evade and suppress the host immune system, exhibited at the levels of antigen recognition and immune activation, limiting the effective signaling between glioma and host immune cells. The second part of the review presents current therapies and their drawbacks. This is followed by a summary of the work of our laboratory during the past 20 years, on oligosaccharide and glycosphingolipid inhibitors of astroblast and astrocytoma division. Neurostatins, the O-acetylated forms of gangliosides GD1b and GT1b naturally present in mammalian brain, are cytostatic for normal astroblasts, but cytotoxic for rat C6 glioma cells and human astrocytoma grades III and IV, with ID50 values ranging from 200 to 450 nM. The inhibitors do not affect neurons or fibroblasts up to concentrations of 4 μM or higher. At least four different neurostatin-activated, cell-mediated antitumoral processes, lead to tumor destruction: (i) inhibition of tumor neovascularization; (ii) activation of microglia; (iii) activation of natural killer (NK) cells; (iv) activation of cytotoxic lymphocytes (CTL). The enhanced antigenicity of neurostatin-treated glioma cells, could be related to their increased expression of connexin 43. Because neurostatins and their analogues show specific activity and no toxicity for normal cells, a clinical trial would be the logical next step. PMID:22084619

Finite Element Analysis of Single Cell Stiffness Measurements Using PZT-Integrated Buckling Nanoneedles

PubMed Central

Rad, Maryam Alsadat; Tijjani, Auwal Shehu; Ahmad, Mohd Ridzuan; Auwal, Shehu Muhammad

2016-01-01

This paper proposes a new technique for real-time single cell stiffness measurement using lead zirconate titanate (PZT)-integrated buckling nanoneedles. The PZT and the buckling part of the nanoneedle have been modelled and validated using the ABAQUS software. The two parts are integrated together to function as a single unit. After calibration, the stiffness, Young’s modulus, Poisson’s ratio and sensitivity of the PZT-integrated buckling nanoneedle have been determined to be 0.7100 N·m−1, 123.4700 GPa, 0.3000 and 0.0693 V·m·N−1, respectively. Three Saccharomyces cerevisiae cells have been modelled and validated based on compression tests. The average global stiffness and Young’s modulus of the cells are determined to be 10.8867 ± 0.0094 N·m−1 and 110.7033 ± 0.0081 MPa, respectively. The nanoneedle and the cell have been assembled to measure the local stiffness of the single Saccharomyces cerevisiae cells The local stiffness, Young’s modulus and PZT output voltage of the three different size Saccharomyces cerevisiae have been determined at different environmental conditions. We investigated that, at low temperature the stiffness value is low to adapt to the change in the environmental condition. As a result, Saccharomyces cerevisiae becomes vulnerable to viral and bacterial attacks. Therefore, the proposed technique will serve as a quick and accurate process to diagnose diseases at early stage in a cell for effective treatment. PMID:28025571

Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

PubMed Central

Nasef, Noha Ahmed; Mehta, Sunali; Powell, Penny; Marlow, Gareth; Wileman, Tom; Ferguson, Lynnette R

2015-01-01

Background Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines. Method Mouse embryonic fibroblasts (MEF) deleted for ATG5, and two intestinal epithelial cells HCT15 and HCT116, were used to test the anti-inflammatory effect of F3 after stimulating the cells with a TLR2 specific ligand PAM3CSK4. Results F3 was able to reduce TLR2 specific inflammation and stimulate autophagy in MEFs and HCT15 cells but not in HCT116 cells. The anti-inflammatory effect was reduced in the MEF cells deleted for ATG5. In addition, the activation of autophagy by F3 was enhanced by PAM3CSK4. Conclusion F3 of feijoa can interact with cells via a TLR2 specific mechanism and reduce Nuclear factor kappa B (NF-κB) activation in part due to stimulation of autophagy. These results suggest that there is potential benefit in using feijoa extracts as part of dietary interventions to manage IBD in patients. PMID:26110654

Biopolymer foams - Relationship between material characteristics and foaming behavior of cellulose based foams

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

Rapp, F., E-mail: florian.rapp@ict.fraunhofer.de, E-mail: anja.schneider@ict.fraunhofer.de; Schneider, A., E-mail: florian.rapp@ict.fraunhofer.de, E-mail: anja.schneider@ict.fraunhofer.de; Elsner, P., E-mail: peter.elsner@ict.fraunhofer.de

2014-05-15

Biopolymers are becoming increasingly important to both industry and consumers. With regard to waste management, CO{sub 2} balance and the conservation of petrochemical resources, increasing efforts are being made to replace standard plastics with bio-based polymers. Nowadays biopolymers can be built for example of cellulose, lactic acid, starch, lignin or bio mass. The paper will present material properties of selected cellulose based polymers (cellulose propionate [CP], cellulose acetate butyrate [CAB]) and corresponding processing conditions for particle foams as well as characterization of produced parts. Special focus is given to the raw material properties by analyzing thermal behavior (differential scanning calorimetry),more » melt strength (Rheotens test) and molecular weight distribution (gel-permeation chromatography). These results will be correlated with the foaming behavior in a continuous extrusion process with physical blowing agents and underwater pelletizer. Process set-up regarding particle foam technology, including extrusion foaming and pre-foaming, will be shown. The characteristics of the resulting foam beads will be analyzed regarding part density, cell morphology and geometry. The molded parts will be tested on thermal conductivity as well as compression behavior (E-modulus, compression strength)« less

Exploring movement and energy in human P-glycoprotein conformational rearrangement.

PubMed

Zhang, Yue; Gong, Weikang; Wang, Yan; Liu, Yang; Li, Chunhua

2018-04-24

Human P-glycoprotein (P-gp), a kind of ATP-Binding Cassette transporter, can export a diverse variety of anti-cancer drugs out of the tumor cell. Its overexpression is one of the main reasons for the multidrug resistance (MDR) of tumor cells. It has been confirmed that during the substrate transport process, P-gp experiences a large-scale structural rearrangement from the inward- to outward-facing states. However, the mechanism of how the nucleotide-binding domains (NBDs) control the transmembrane domains (TMDs) to open towards the periplasm in the outward-facing state has not yet been fully characterized. Herein, targeted molecular dynamics simulations were performed to explore the conformational rearrangement of human P-gp. The results show that the allosteric process proceeds in a coupled way, and first the transition is driven by the NBDs, and then transmitted to the cytoplasmic parts of TMDs, finally to the periplasmic parts. The trajectories show that besides the translational motions, the NBDs undergo a rotation movement, which mainly occurs in xy plane and ensures the formation of the correct ATP-binding pockets. The analyses on the interaction energies between the six structure segments (cICLs) from the TMDs and NBDs reveal that their subtle energy differences play an important role in causing the periplasmic parts of the transmembrane helices to separate from each other in the established directions and in appropriate amplitudes. This conclusion can explain the two experimental phenomena about human P-gp in some extent. These studies have provided a detailed exploration into human P-gp rearrangement process and given an energy insight into the TMD reorientation during P-gp transition.

Endogenous antigen tunes the responsiveness of naive B cells but not T cells

PubMed Central

Zikherman, Julie; Parameswaran, Ramya; Weiss, Arthur

2012-01-01

In humans up to 75% of newly generated B cells and about 30% of mature B cells exhibit some degree of autoreactivity1. Yet, how B cells establish and maintain tolerance in the face of autoantigen exposure during and after development is not certain. Studies of model BCR transgenic systems have highlighted the critical role played by functional unresponsiveness or ‘anergy’2,3. Unlike T cells, evidence suggests that receptor editing and anergy, rather than deletion, account for much of B cell tolerance4,5. However, it remains unclear whether the mature diverse B cell repertoire of mice contains anergic autoreactive B cells, and if so, whether antigen was encountered during or after their development. By taking advantage of a reporter mouse in which B cell antigen receptor (BCR) signaling rapidly and robustly induces GFP expression under the control of the Nur77 regulatory region, antigen-dependent and – independent BCR signaling events in vivo during B cell maturation were visualized. Here we show that B cells encounter antigen during development in the spleen, and that this antigen exposure in turn tunes the responsiveness of BCR signaling in B cells at least partly by down-modulating expression of surface IgM but not IgD BCRs, and by modifying basal calcium levels. By contrast, no analogous process occurs in naive mature T cells. Our data demonstrate not only that autoreactive B cells persist in the mature repertoire, but that functional unresponsiveness or ‘anergy’ exists in the mature B cell repertoire along a continuum, a fact that has long been suspected, but never yet shown. These results have important implications for understanding how tolerance in T and B cells is differently imposed, and how these processes might go awry in disease. PMID:22902503

Microscale localization and isolation of light emitting imperfections in monocrystalline silicon solar cells

NASA Astrophysics Data System (ADS)

Gajdoš, Adam; Škvarenina, Lubomír.; Škarvada, Pavel; Macků, Robert

2017-12-01

An imperfections or defects may appear in fabricated monocrystalline solar cells. These microstructural imperfections could have impact on the parameters of whole solar cell. The research is divided into two parts, firstly, the detection and localization defects by using several techniques including current-voltage measurement, scanning probe microscopy (SPM), scanning electron microscope (SEM) and electroluminescence. Secondly, the defects isolation by a focused ion beam (FIB) milling and impact of a milling process on solar cells. The defect detection is realized by I-V measurement under reverse biased sample. For purpose of localization, advantage of the fact that defects or imperfections in silicon solar cells emit the visible and near infrared electroluminescence under reverse biased voltage is taken, and CCD camera measurement for macroscopic localization of these spots is applied. After rough macroscopic localization, microscopic localization by scanning probe microscopy combined with a photomultiplier (shadow mapping) is performed. Defect isolation is performed by a SEM equipped with the FIB instrument. FIB uses a beam of gallium ions which modifies crystal structure of a material and may affect parameters of solar cell. As a result, it is interesting that current in reverse biased sample with isolated defect is smaller approximately by 2 orders than current before isolation process.

Non-apoptotic cell death in animal development.

PubMed

Kutscher, Lena M; Shaham, Shai

2017-08-01

Programmed cell death (PCD) is an important process in the development of multicellular organisms. Apoptosis, a form of PCD characterized morphologically by chromatin condensation, membrane blebbing, and cytoplasm compaction, and molecularly by the activation of caspase proteases, has been extensively investigated. Studies in Caenorhabditis elegans, Drosophila, mice, and the developing chick have revealed, however, that developmental PCD also occurs through other mechanisms, morphologically and molecularly distinct from apoptosis. Some non-apoptotic PCD pathways, including those regulating germ cell death in Drosophila, still appear to employ caspases. However, another prominent cell death program, linker cell-type death (LCD), is morphologically conserved, and independent of the key genes that drive apoptosis, functioning, at least in part, through the ubiquitin proteasome system. These non-apoptotic processes may serve as backup programs when caspases are inactivated or unavailable, or, more likely, as freestanding cell culling programs. Non-apoptotic PCD has been documented extensively in the developing nervous system, and during the formation of germline and somatic gonadal structures, suggesting that preservation of these mechanisms is likely under strong selective pressure. Here, we discuss our current understanding of non-apoptotic PCD in animal development, and explore possible roles for LCD and other non-apoptotic developmental pathways in vertebrates. We raise the possibility that during vertebrate development, apoptosis may not be the major PCD mechanism.

A single cell penetration system by ultrasonic driving

NASA Astrophysics Data System (ADS)

Zhou, Zhaoying; Xiao, Mingfei; Yang, Xing; Wu, Ting

2008-12-01

The researches of single cell's control and operation are the hotspots in whole world. Among the various technologies, the transmission of ectogenic genetic materials between cell membrane is very significant. Imitating the Chinese traditional acupuncture therapy, a new ultrasonic resonance driving method, is imported to drive a cell's penetration probe. A set of the single cell penetration system was established to perform this function. This system includes four subsystems: driving part, micromanipulation part, observation and measurement part, and actuation part. Some fish egg experiments indicate that this system is workable and effective.

Review of free software tools for image analysis of fluorescence cell micrographs.

PubMed

Wiesmann, V; Franz, D; Held, C; Münzenmayer, C; Palmisano, R; Wittenberg, T

2015-01-01

An increasing number of free software tools have been made available for the evaluation of fluorescence cell micrographs. The main users are biologists and related life scientists with no or little knowledge of image processing. In this review, we give an overview of available tools and guidelines about which tools the users should use to segment fluorescence micrographs. We selected 15 free tools and divided them into stand-alone, Matlab-based, ImageJ-based, free demo versions of commercial tools and data sharing tools. The review consists of two parts: First, we developed a criteria catalogue and rated the tools regarding structural requirements, functionality (flexibility, segmentation and image processing filters) and usability (documentation, data management, usability and visualization). Second, we performed an image processing case study with four representative fluorescence micrograph segmentation tasks with figure-ground and cell separation. The tools display a wide range of functionality and usability. In the image processing case study, we were able to perform figure-ground separation in all micrographs using mainly thresholding. Cell separation was not possible with most of the tools, because cell separation methods are provided only by a subset of the tools and are difficult to parametrize and to use. Most important is that the usability matches the functionality of a tool. To be usable, specialized tools with less functionality need to fulfill less usability criteria, whereas multipurpose tools need a well-structured menu and intuitive graphical user interface. © 2014 Fraunhofer-Institute for Integrated Circuits IIS Journal of Microscopy © 2014 Royal Microscopical Society.

Corilagin from longan seed: Identification, quantification, and synergistic cytotoxicity on SKOv3ip and hey cells with ginsenoside Rh2 and 5-fluorouracil.

PubMed

Li, Ni; Lin, Zhican; Chen, Wei; Zheng, Yi; Ming, Yanlin; Zheng, Zhizhong; Huang, Wen; Chen, Lianghua; Xiao, Jianbo; Lin, Hetong

2018-05-08

Corilagin content from different parts of longan (Dimocarpus longan Lour.) was determined by ultra performance liquid chromatography (UPLC) method. Additionally, the potential synergistic effects of corilagin + ginsenoside Rh2 (Rh2), and corilagin + 5-fluorouracil (5-FU) on ovarian cancer cells, and cancer-preventing activities, including inhibition of tyrosinase, properties of antioxidant and nitrite-scavenging, and blocking of nitrosamine synthesis were investigated. The results showed the content of corilagin from different parts of longan varied widely, while corilagin content in longan seed was high with a value of 542.15 ± 10.30 μg/g. Then the corilagin from longan seed was chosen for further study, since longan seed was easily obtained from by-product of longan fruit processing with low cost. Furthermore, the combinations of corilagin + Rh2, and corilagin + 5-FU showed an increased synergistic cytotoxicity on SKOv3ip and Hey cells. Moreover, corilagin inhibited exhibited effects of inhibiting tyrosinase, antioxidation, scavenging nitrite and blocking nitrosamine synthesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Crystallographic Insights into the Autocatalytic Assembly Mechanism of a Bacteriophage Tail Spike

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

Xiang, Ye; Leiman, Petr G.; Li, Long

2010-02-03

The tailed bacteriophage phi29 has 12 'appendages' (gene product 12, gp12) attached to its neck region that participate in host cell recognition and entry. In the cell, monomeric gp12 undergoes proteolytic processing that releases the C-terminal domain during assembly into trimers. We report here crystal structures of the protein before and after catalytic processing and show that the C-terminal domain of gp12 is an 'autochaperone' that aids trimerization. We also show that autocleavage of the C-terminal domain is a posttrimerization event that is followed by a unique ATP-dependent release. The posttranslationally modified N-terminal part has three domains that function tomore » attach the appendages to the phage, digest the cell wall teichoic acids, and bind irreversibly to the host, respectively. Structural and sequence comparisons suggest that some eukaryotic and bacterial viruses as well as bacterial adhesins might have a similar maturation mechanism as is performed by phi29 gp12 for Bacillus subtilis.« less

Commercialisation of CMOS integrated circuit technology in multi-electrode arrays for neuroscience and cell-based biosensors.

PubMed

Graham, Anthony H D; Robbins, Jon; Bowen, Chris R; Taylor, John

2011-01-01

The adaptation of standard integrated circuit (IC) technology as a transducer in cell-based biosensors in drug discovery pharmacology, neural interface systems and electrophysiology requires electrodes that are electrochemically stable, biocompatible and affordable. Unfortunately, the ubiquitous Complementary Metal Oxide Semiconductor (CMOS) IC technology does not meet the first of these requirements. For devices intended only for research, modification of CMOS by post-processing using cleanroom facilities has been achieved. However, to enable adoption of CMOS as a basis for commercial biosensors, the economies of scale of CMOS fabrication must be maintained by using only low-cost post-processing techniques. This review highlights the methodologies employed in cell-based biosensor design where CMOS-based integrated circuits (ICs) form an integral part of the transducer system. Particular emphasis will be placed on the application of multi-electrode arrays for in vitro neuroscience applications. Identifying suitable IC packaging methods presents further significant challenges when considering specific applications. The various challenges and difficulties are reviewed and some potential solutions are presented.

A novel cell autolysis system for cost-competitive downstream processing.

PubMed

Hajnal, Ivan; Chen, Xiangbin; Chen, Guo-Qiang

2016-11-01

The industrial production of low value-added biological products poses significant challenges due to cost pressures. In recent years, it has been argued that synthetic biology approaches will lead to breakthroughs that eliminate price bottlenecks for the production of a wide range of biological products including bioplastics and biofuels. One significant bottleneck lies in the necessity to break the tough cell walls of microbes in order to release intracellular products. We here report the implementation of the first synthetic biology standard part based on the lambda phage SRRz genes and a synthetic ribosome binding site (RBS) that works in Escherichia coli and Halomonas campaniensis, which enables the producer strains to induce lysis after the addition of small amounts (1-5 %) of solvents or to spontaneously lyse during the stresses of downstream processing, and thus has the potential to eliminate the mechanical cell disruption step as both an efficiency bottleneck and a significant capex barrier when implementing downstream bioprocesses.

Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds

PubMed Central

Marfia, Giovanni; Navone, Stefania Elena; Di Vito, Clara; Ughi, Nicola; Tabano, Silvia; Miozzo, Monica; Tremolada, Carlo; Bolla, Gianni; Crotti, Chiara; Ingegnoli, Francesca; Rampini, Paolo; Riboni, Laura; Gualtierotti, Roberta; Campanella, Rolando

2015-01-01

abstract Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances. PMID:26652928

CellStress - open source image analysis program for single-cell analysis

NASA Astrophysics Data System (ADS)

Smedh, Maria; Beck, Caroline; Sott, Kristin; Goksör, Mattias

2010-08-01

This work describes our image-analysis software, CellStress, which has been developed in Matlab and is issued under a GPL license. CellStress was developed in order to analyze migration of fluorescent proteins inside single cells during changing environmental conditions. CellStress can also be used to score information regarding protein aggregation in single cells over time, which is especially useful when monitoring cell signaling pathways involved in e.g. Alzheimer's or Huntington's disease. Parallel single-cell analysis of large numbers of cells is an important part of the research conducted in systems biology and quantitative biology in order to mathematically describe cellular processes. To quantify properties for single cells, large amounts of data acquired during extended time periods are needed. Manual analyses of such data involve huge efforts and could also include a bias, which complicates the use and comparison of data for further simulations or modeling. Therefore, it is necessary to have an automated and unbiased image analysis procedure, which is the aim of CellStress. CellStress utilizes cell contours detected by CellStat (developed at Fraunhofer-Chalmers Centre), which identifies cell boundaries using bright field images, and thus reduces the fluorescent labeling needed.

Nuclear Functions of Actin

PubMed Central

Visa, Neus; Percipalle, Piergiorgio

2010-01-01

Actin participates in several essential processes in the cell nucleus. Even though the presence of actin in the nucleus was proposed more than 30 years ago, nuclear processes that require actin have been only recently identified. Actin is part of chromatin remodeling complexes; it is associated with the transcription machineries; it becomes incorporated into newly synthesized ribonucleoproteins; and it influences long-range chromatin organization. As in the cytoplasm, nuclear actin works in conjunction with different types of actin-binding proteins that regulate actin function and bridge interactions between actin and other nuclear components. PMID:20452941

Application of evolutionary games to modeling carcinogenesis.

PubMed

Swierniak, Andrzej; Krzeslak, Michal

2013-06-01

We review a quite large volume of literature concerning mathematical modelling of processes related to carcinogenesis and the growth of cancer cell populations based on the theory of evolutionary games. This review, although partly idiosyncratic, covers such major areas of cancer-related phenomena as production of cytotoxins, avoidance of apoptosis, production of growth factors, motility and invasion, and intra- and extracellular signaling. We discuss the results of other authors and append to them some additional results of our own simulations dealing with the possible dynamics and/or spatial distribution of the processes discussed.

Selective heterogeneity in exoprotease production by Bacillus subtilis.

PubMed

Davidson, Fordyce A; Seon-Yi, Chung; Stanley-Wall, Nicola R

2012-01-01

Bacteria have elaborate signalling mechanisms to ensure a behavioural response that is most likely to enhance survival in a changing environment. It is becoming increasingly apparent that as part of this response, bacteria are capable of cell differentiation and can generate multiple, mutually exclusive co-existing cell states. These cell states are often associated with multicellular processes that bring benefit to the community as a whole but which may be, paradoxically, disadvantageous to an individual subpopulation. How this process of cell differentiation is controlled is intriguing and remains a largely open question. In this paper, we consider an important aspect of cell differentiation that is known to occur in the gram-positive bacterium Bacillus subtilis: we investigate the role of two master regulators DegU and Spo0A in the control of extra-cellular protease production. Recent work in this area focussed the on role of DegU in this process and suggested that transient effects in protein production were the drivers of cell-response heterogeneity. Here, using a combination of mathematical modelling, analysis and stochastic simulations, we provide a complementary analysis of this regulatory system that investigates the roles of both DegU and Spo0A in extra-cellular protease production. In doing so, we present a mechanism for bimodality, or system heterogeneity, without the need for a bistable switch in the underlying regulatory network. Moreover, our analysis leads us to conclude that this heterogeneity is in fact a persistent, stable feature. Our results suggest that system response is divided into three zones: low and high signal levels induce a unimodal or undifferentiated response from the cell population with all cells OFF and ON, respectively for exoprotease production. However, for intermediate levels of signal, a heterogeneous response is predicted with a spread of activity levels, representing typical "bet-hedging" behaviour.

Follicular T helper cells and IL-21 in rheumatic diseases.

PubMed

Rasmussen, Tue Kruse

2016-10-01

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life. At the heart of the disease mechanisms in RA and SLE are subsets of immune cells called T and B cells. These cell types produce proteins (called antibodies), which under normal circumstances protect the body against disease. In RA and SLE these cells produce antibodies that are directed at the bodies own tissues (called autoantibodies), causing inflammation and tissue damage. The cause of this loss of tolerance is still unknown. Interleukin 21 (IL-21) is thought to exert key functions in controlling and directing the T and B cell responses leading to formation of antibodies and autoantibodies alike. IL-21 is a signaling molecule secreted by a subpopulation of T cells called follicular T helper (Tfh) cells. IFNα is another signaling molecule of key importance in autoimmune disease. Stratification of SLE patients by their responsiveness to IFNα has proven a crucial tool in stratifying patients in terms of disease development and treatment response. The aim of this PhD study is to investigate the role of IL-21 and IFNα, and their effects on Tfh cells and B cells and the formation of autoantibodies in RA and SLE. The first part of this study addresses whether plasma levels of IL-21 influence disease activity in rheumatic disease. We further investigate the distribution of IL-21-producing Tfh cells in these patients. We find that IL-21 plasma levels correlate to disease activity and radiological progression in RA, and that the IL-21-producing Tfh cell are increased in the blood and synovial fluid of these patients. These findings support the idea that IL-21 and Tfh cells are linked to the development and perpetuation of these diseases. In the second part of this we investigate how small RNA molecules, called microRNAs, can regulate immunological processes. We find that microRNA-155 can regulate IL-21's capacity to signal, while microRNA-21 is important for survival of T cells. The third, and last part of this, concerns IFNα signaling and its impact on the development of SLE and the formation of autoantibodies. We find that IFNα signaling is altered in a murine model of SLE, and that inhibition of this signaling pathway leads to severe kidney disease. The latter is of key importance as inhibition of IFNα is currently in early trial as a new treatment form for SLE patients. In SLE patients, we find that IFNα responsiveness, as measured by a so-called IFN signature, is crucial in terms of development of the disease as well as serious complications such as kidney disease and involvement of the central nervous system. Interferon alpha does this by affecting intracellular signaling responses and the formation of autoantibodies. The data presented in this thesis supports that IL-21 and Tfh cells have a key role in the disease processes characterizing RA and SLE. We further describe a novel mechanism for microRNA-155 and microRNA-21 in regulating immunological processes in these diseases. Finally we show, that IFNα has important functions in the formation of autoantibodies in SLE. In conclusion, this thesis adds new and important knowledge on the interplay between Tfh cells and B cells and their formation of autoantibodies in rheumatic disease. This knowledge will guide and further the development of new treatment strategies to better patient outcome.

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In vitro decidualisation of canine uterine stromal cells.

PubMed

Kautz, Ewa; de Carvalho Papa, Paula; Reichler, Iris M; Gram, Aykut; Boos, Alois; Kowalewski, Mariusz P

2015-08-05

The uterine response to the presence of embryos is poorly understood in the domestic dog (Canis familiaris). The intimate embryo-maternal cross-talk, which begins following the hatching of blastocysts and embryo attachment leads to strong structural and functional remodelling of the uterus. A part of this process is decidualisation, comprising morphological and biochemical changes that result in formation of maternal stroma-derived decidual cells. These are an integral part of the canine placenta materna, which together with the maternal vascular endothelium are the only cells of the canine endotheliochorial placenta able to resist trophoblast invasion. These cells are also the only ones within the canine placenta expressing the progesterone receptor (PGR). Understanding the decidualisation process thus appears essential for understanding canine reproductive physiology. Here, we investigated the capability of canine uterine stromal cells to decidualise in vitro, thereby serving as a canine model of decidualisation. A dbcAMP-mediated approach was chosen during a time course of 24 - 72 h. Tissue material from six (n = 6) healthy, dioestric bitches was used (approximately 2 weeks after ovulation). Cells were characterized by differential staining, nearly 100 % of which were vimentin-positive. Scanning and transmission electron microscope analyses were applied, and morphological changes were recorded with a live cell imaging microscope. Expression of several decidualisation markers was investigated. The in vitro cultured stromal cells acquired characteristics of decidual cells when incubated with 0.5 mM dbcAMP for 72 h. Their shape changed from elongated to rounded, while ultrastructural analysis revealed higher numbers of mitochondria and secretory follicles, and an increased proliferation rate. Elevated expression levels of IGF1, IGF2, PRLR and ERα were observed in decidualised cells; PRL and ERβ remained mostly below the detection limit, while PGR remained unaffected. The expression of smooth muscle α actin (αSMA), another decidualisation marker, was strongly induced. Among prostaglandin system members, levels of COX2 (PTGS2) and of PGE2-synthase (PTGES) were upregulated. Expression of the PGE2 receptors, PTGER2 and PTGER4, was clearly detectable. An in vitro decidualisation model with canine uterine stromal cells was successfully established, allowing future, more detailed studies to be undertaken on the underlying molecular and endocrine mechanisms of canine decidualisation.

Gene expression profile in human induced pluripotent stem cells: Chondrogenic differentiation in vitro, part A

PubMed Central

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Richter, Magdalena; Trzeciak, Tomasz

2017-01-01

Human induced pluripotent stem cells (hiPSCs) offer promise in regenerative medicine, however more data are required to improve understanding of key aspects of the cell differentiation process, including how specific chondrogenic processes affect the gene expression profile of chondrocyte-like cells and the relative value of cell differentiation markers. The main aims of the present study were as follows: To determine the gene expression profile of chondrogenic-like cells derived from hiPSCs cultured in mediums conditioned with HC-402-05a cells or supplemented with transforming growth factor β3 (TGF-β3), and to assess the relative utility of the most commonly used chondrogenic markers as indicators of cell differentiation. These issues are relevant with regard to the use of human fibroblasts in the reprogramming process to obtain hiPSCs. Human fibroblasts are derived from the mesoderm and thus share a wide range of properties with chondrocytes, which also originate from the mesenchyme. Thus, the exclusion of dedifferentiation instead of chondrogenic differentiation is crucial. The hiPSCs were obtained from human primary dermal fibroblasts during a reprogramming process. Two methods, both involving embryoid bodies (EB), were used to obtain chondrocytes from the hiPSCs: EBs formed in a chondrogenic medium supplemented with TGF-β3 (10 ng/ml) and EBs formed in a medium conditioned with growth factors from HC-402-05a cells. Based on immunofluorescence and reverse transcription-quantiative polymerase chain reaction analysis, the results indicated that hiPSCs have the capacity for effective chondrogenic differentiation, in particular cells differentiated in the HC-402-05a-conditioned medium, which present morphological features and markers that are characteristic of mature human chondrocytes. By contrast, cells differentiated in the presence of TGF-β3 may demonstrate hypertrophic characteristics. Several genes [paired box 9, sex determining region Y-box (SOX) 5, SOX6, SOX9 and cartilage oligomeric matrix protein] were demonstrated to be good markers of early hiPSC chondrogenic differentiation: Insulin-like growth factor 1, Tenascin-C, and β-catenin were less valuable. These observations provide valuable data on the use of hiPSCs in cartilage tissue regeneration. PMID:28447755

Identification of genes involved in the ACC-mediated control of root cell elongation in Arabidopsis thaliana

PubMed Central

2012-01-01

Background Along the root axis of Arabidopsis thaliana, cells pass through different developmental stages. In the apical meristem repeated cycles of division increase the numbers of cells. Upon leaving the meristem, these cells pass the transition zone where they are physiologically and mechanically prepared to undergo subsequent rapid elongation. During the process of elongation epidermal cells increase their length by 300% in a couple of hours. When elongation ceases, the cells acquire their final size, shape and functions (in the differentiation zone). Ethylene administered as its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) is capable of inhibiting elongation in a concentration-dependent way. Using a microarray analysis, genes and/or processes involved in this elongation arrest are identified. Results Using a CATMA-microarray analysis performed on control and 3h ACC-treated roots, 240 differentially expressed genes were identified. Quantitative Real-Time RT-PCR analysis of the 10 most up and down regulated genes combined with literature search confirmed the accurateness of the analysis. This revealed that inhibition of cell elongation is, at least partly, caused by restricting the events that under normal growth conditions initiate elongation and by increasing the processes that normally stop cellular elongation at the end of the elongation/onset of differentiation zone. Conclusions ACC interferes with cell elongation in the Arabidopsis thaliana roots by inhibiting cells from entering the elongation process and by immediately stimulating the formation of cross-links in cell wall components, diminishing the remaining elongation capacity. From the analysis of the differentially expressed genes, it becomes clear that many genes identified in this response, are also involved in several other kind of stress responses. This suggests that many responses originate from individual elicitors, but that somewhere in the downstream signaling cascade, these are converged to a ’common pathway’. Furthermore, several potential keyplayers, such as transcription factors and auxin-responsive genes, were identified by the microarray analysis. They await further analysis to reveal their exact role in the control of cell elongation. PMID:23134674

Generalized Uncertainty Principle and Parikh-Wilczek Tunneling

NASA Astrophysics Data System (ADS)

Mehdipour, S. Hamid

We investigate the modifications of the Hawking radiation by the Generalized Uncertainty Principle (GUP) and the tunneling process. By using the GUP-corrected de Broglie wavelength, the squeezing of the fundamental momentum cell, and consequently a GUP-corrected energy, we find the nonthermal effects which lead to a nonzero statistical correlation function between probabilities of tunneling of two massive particles with different energies. Then the recovery of part of the information from the black hole radiation is feasible. From the other point of view, the inclusion of the effects of quantum gravity as the GUP expression can halt the evaporation process, so that a stable black hole remnant is left behind, including the other part of the black hole information content. Therefore, these features of the Planck-scale corrections may solve the information problem in black hole evaporation.

SRB Processing Facilities Media Event

NASA Image and Video Library

2016-03-01

The right-hand aft skirt, one part of the aft booster assembly for NASA’s Space Launch System solid rocket boosters, is in view in a processing cell inside the Booster Fabrication Facility (BFF) at NASA’s Kennedy Space Center in Florida. Orbital ATK is a contractor for NASA’s Marshall Space Flight Center in Alabama, and operates the BFF to prepare aft booster segments and hardware for the SLS rocket boosters. The SLS rocket and Orion spacecraft will launch on Exploration Mission-1 in 2018. The Ground Systems Development and Operations Program is preparing the infrastructure to process and launch spacecraft for deep-space missions and the journey to Mars.

Live imaging reveals the progenitors and cell dynamics of limb regeneration

PubMed Central

Alwes, Frederike; Enjolras, Camille; Averof, Michalis

2016-01-01

Regeneration is a complex and dynamic process, mobilizing diverse cell types and remodelling tissues over long time periods. Tracking cell fate and behaviour during regeneration in active adult animals is especially challenging. Here, we establish continuous live imaging of leg regeneration at single-cell resolution in the crustacean Parhyale hawaiensis. By live recordings encompassing the first 4-5 days after amputation, we capture the cellular events that contribute to wound closure and morphogenesis of regenerating legs with unprecedented resolution and temporal detail. Using these recordings we are able to track cell lineages, to generate fate maps of the blastema and to identify the progenitors of regenerated epidermis. We find that there are no specialized stem cells for the epidermis. Most epidermal cells in the distal part of the leg stump proliferate, acquire new positional values and contribute to new segments in the regenerating leg. DOI: http://dx.doi.org/10.7554/eLife.19766.001 PMID:27776632

Developing defined substrates for stem cell culture and differentiation.

PubMed

Hagbard, Louise; Cameron, Katherine; August, Paul; Penton, Christopher; Parmar, Malin; Hay, David C; Kallur, Therése

2018-07-05

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro , but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell-matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Authors.

Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part I: from three-dimensional cell growth to biomimetics of in vivo development.

PubMed

Lenas, Petros; Moos, Malcolm; Luyten, Frank P

2009-12-01

Recent advances in developmental biology, systems biology, and network science are converging to poise the heretofore largely empirical field of tissue engineering on the brink of a metamorphosis into a rigorous discipline based on universally accepted engineering principles of quality by design. Failure of more simplistic approaches to the manufacture of cell-based therapies has led to increasing appreciation of the need to imitate, at least to some degree, natural mechanisms that control cell fate and differentiation. The identification of many of these mechanisms, which in general are based on cell signaling pathways, is an important step in this direction. Some well-accepted empirical concepts of developmental biology, such as path-dependence, robustness, modularity, and semiautonomy of intermediate tissue forms, that appear sequentially during tissue development are starting to be incorporated in process design.

Subcutaneous soft tissue sarcoma with rhabdoid features in a dog.

PubMed

Sayama, Ayako; Okado, Keiko; Imaoka, Masako; Yokouchi, Yusuke; Jindo, Toshimasa; Takasaki, Wataru

2014-07-01

A nine-year-old male beagle dog had a white spherical mass in the subcutis of the left lumbar region. Microscopically, spindle to oval cells diffusely proliferated in the fibrous and myxoid stroma. Many neoplastic cells showed rhabdoid features or vacuolated cytoplasm. Immunohistochemically, the neoplastic cells were positive for vimentin and S100 and partly positive for neuron-specific enolase and glial fibrillary acidic protein but were negative for von Willebrand factor, desmin and α-smooth muscle actin. Ultrastructurally, the neoplastic cells had abundant cytoplasmic processes and desmosome-like structures. Cytoplasmic inclusions of rhabdoid-featured cells in HE sections were composed of aggregates of intermediate filaments, and cytoplasmic vacuoles were identified as an invagination of cytoplasm. Although malignant peripheral nerve sheath tumor was suggested according to these results, the present case was diagnosed as a soft tissue sarcoma with rhabdoid features due to a lack of identification of the basal lamina under electron microscopy.

Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.

PubMed

Newman, Rebecca; Ahlfors, Helena; Saveliev, Alexander; Galloway, Alison; Hodson, Daniel J; Williams, Robert; Besra, Gurdyal S; Cook, Charlotte N; Cunningham, Adam F; Bell, Sarah E; Turner, Martin

2017-06-01

RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.

Maintenance of the marginal zone B cell compartment specifically requires the RNA-binding protein ZFP36L1

PubMed Central

Newman, Rebecca; Ahlfors, Helena; Saveliev, Alexander; Galloway, Alison; Hodson, Daniel J; Williams, Robert; Besra, Gurdyal S.; Cook, Charlotte N; Cunningham, Adam F; Bell, Sarah E; Turner, Martin

2017-01-01

RNA binding proteins (RBP) of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU rich elements in the 3’UTR and promoting mRNA decay. Here we show an indispensible role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal zone (MZ) B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene expression program related to signaling, cell-adhesion and locomotion, in part by limiting the expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RBP for maintaining cellular identity between closely related cell types. PMID:28394372

Subcutaneous Soft Tissue Sarcoma with Rhabdoid Features in a Dog

PubMed Central

Sayama, Ayako; Okado, Keiko; Imaoka, Masako; Yokouchi, Yusuke; Jindo, Toshimasa; Takasaki, Wataru

2014-01-01

A nine-year-old male beagle dog had a white spherical mass in the subcutis of the left lumbar region. Microscopically, spindle to oval cells diffusely proliferated in the fibrous and myxoid stroma. Many neoplastic cells showed rhabdoid features or vacuolated cytoplasm. Immunohistochemically, the neoplastic cells were positive for vimentin and S100 and partly positive for neuron-specific enolase and glial fibrillary acidic protein but were negative for von Willebrand factor, desmin and α-smooth muscle actin. Ultrastructurally, the neoplastic cells had abundant cytoplasmic processes and desmosome-like structures. Cytoplasmic inclusions of rhabdoid-featured cells in HE sections were composed of aggregates of intermediate filaments, and cytoplasmic vacuoles were identified as an invagination of cytoplasm. Although malignant peripheral nerve sheath tumor was suggested according to these results, the present case was diagnosed as a soft tissue sarcoma with rhabdoid features due to a lack of identification of the basal lamina under electron microscopy. PMID:25352714

A review on the performance and modelling of proton exchange membrane fuel cells

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

Boucetta, A., E-mail: abirboucetta@yahoo.fr; Ghodbane, H., E-mail: h.ghodbane@mselab.org; Bahri, M., E-mail: m.bahri@mselab.org

2016-07-25

Proton Exchange Membrane Fuel Cells (PEMFC), are energy efficient and environmentally friendly alternative to conventional energy conversion for various applications in stationary power plants, portable power device and transportation. PEM fuel cells provide low operating temperature and high-energy efficiency with near zero emission. A PEM fuel cell is a multiple distinct parts device and a series of mass, energy, transport through gas channels, electric current transport through membrane electrode assembly and electrochemical reactions at the triple-phase boundaries. These processes play a decisive role in determining the performance of the Fuel cell, so that studies on the phenomena of gas flowsmore » and the performance modelling are made deeply. This paper gives a comprehensive overview of the state of the art on the Study of the phenomena of gas flow and performance modelling of PEMFC.« less

Plant cell wall characterization using scanning probe microscopy techniques

PubMed Central

Yarbrough, John M; Himmel, Michael E; Ding, Shi-You

2009-01-01

Lignocellulosic biomass is today considered a promising renewable resource for bioenergy production. A combined chemical and biological process is currently under consideration for the conversion of polysaccharides from plant cell wall materials, mainly cellulose and hemicelluloses, to simple sugars that can be fermented to biofuels. Native plant cellulose forms nanometer-scale microfibrils that are embedded in a polymeric network of hemicelluloses, pectins, and lignins; this explains, in part, the recalcitrance of biomass to deconstruction. The chemical and structural characteristics of these plant cell wall constituents remain largely unknown today. Scanning probe microscopy techniques, particularly atomic force microscopy and its application in characterizing plant cell wall structure, are reviewed here. We also further discuss future developments based on scanning probe microscopy techniques that combine linear and nonlinear optical techniques to characterize plant cell wall nanometer-scale structures, specifically apertureless near-field scanning optical microscopy and coherent anti-Stokes Raman scattering microscopy. PMID:19703302

Cellular generators of the binaural difference potential in cat.

PubMed

Melcher, J R

1996-05-01

In humans, lateralization and fusion of binaurally presented clicks are correlated with the latency and amplitude of the binaural difference potential (BDP) (e.g., Furst et al., 1985). The BDP is derived by subtracting the brainstem auditory evoked potential (BAEP) for binaural stimulation from the sum of the BAEPs for left and right monaural stimulation. Our aim in this work was to determine the cellular generators of the BDP and thus identify cells that may be crucial for specific types of binaural sound processing. To this end, we injected kainic acid into the superior olivary complex (SOC) or the cochlear nucleus (CN) in cats and examined the effects of the resulting lesions on the click-evoked BDP. Lesions confined to the anterior anteroventral CN (AVCNa) substantially reduced the BDP, while lesions primarily involving more posterior parts of the CN had little or no effect. BDP reductions occurred for lesions involving either high (> 10 kHz) or lower (< 10 kHz) characteristic frequency (CF) regions of the AVCNa (as well as the posterior CN). Lesions involving the SOC reduced the BDP and, in one case, eliminated the high-pass filtered (270 Hz cutoff) BDP. Combining these results with published information about the physiology and anatomy of auditory brainstem cells, we conclude that: (1) spherical cells in the AVCNa are essential for BDP production, (2) the earliest part of the BDP is generated by medial superior olive (MSO) principal cells which receive spherical cell inputs, (3) a later part is probably generated by the cellular targets of MSO principal cells and, (4) the cells involved in BDP generation have CFs above, as well as below, 10 kHz. Since humans, like cats, have a well-developed MSO, we suggest that the MSO may also be essential for BDP production in humans. Thus, perceptual correlates of the BDP, binaural fusion and click lateralization, apparently involve the MSO.

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

PubMed

Demirci, Selami; Doğan, Ayşegül; Apdik, Hüseyin; Tuysuz, Emre Can; Gulluoglu, Sukru; Bayrak, Omer Faruk; Şahin, Fikrettin

2018-01-01

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila.

PubMed

Timmons, Allison K; Mondragon, Albert A; Meehan, Tracy L; McCall, Kimberly

2017-04-03

Programmed cell death occurs as a normal part of oocyte development in Drosophila. For each egg that is formed, 15 germline-derived nurse cells transfer their cytoplasmic contents into the oocyte and die. Disruption of apoptosis or autophagy only partially inhibits the death of the nurse cells, indicating that other mechanisms significantly contribute to nurse cell death. Recently, we demonstrated that the surrounding stretch follicle cells non-autonomously promote nurse cell death during late oogenesis and that phagocytosis genes including draper, ced-12, and the JNK pathway are crucial for this process. When phagocytosis genes are inhibited in the follicle cells, events specifically associated with death of the nurse cells are impaired. Death of the nurse cells is not completely blocked in draper mutants, suggesting that other engulfment receptors are involved. Indeed, we found that the integrin subunit, αPS3, is enriched on stretch follicle cells during late oogenesis and is required for elimination of the nurse cells. Moreover, double mutant analysis revealed that integrins act in parallel to draper. Death of nurse cells in the Drosophila ovary is a unique example of programmed cell death that is both non-apoptotic and non-cell autonomously controlled.

Full-Process Computer Model of Magnetron Sputter, Part I: Test Existing State-of-Art Components

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

Walton, C C; Gilmer, G H; Wemhoff, A P

2007-09-26

This work is part of a larger project to develop a modeling capability for magnetron sputter deposition. The process is divided into four steps: plasma transport, target sputter, neutral gas and sputtered atom transport, and film growth, shown schematically in Fig. 1. Each of these is simulated separately in this Part 1 of the project, which is jointly funded between CMLS and Engineering. The Engineering portion is the plasma modeling, in step 1. The plasma modeling was performed using the Object-Oriented Particle-In-Cell code (OOPIC) from UC Berkeley [1]. Figure 2 shows the electron density in the simulated region, using magneticmore » field strength input from experiments by Bohlmark [2], where a scale of 1% is used. Figures 3 and 4 depict the magnetic field components that were generated using two-dimensional linear interpolation of Bohlmark's experimental data. The goal of the overall modeling tool is to understand, and later predict, relationships between parameters of film deposition we can change (such as gas pressure, gun voltage, and target-substrate distance) and key properties of the results (such as film stress, density, and stoichiometry.) The simulation must use existing codes, either open-source or low-cost, not develop new codes. In part 1 (FY07) we identified and tested the best available code for each process step, then determined if it can cover the size and time scales we need in reasonable computation times. We also had to determine if the process steps are sufficiently decoupled that they can be treated separately, and identify any research-level issues preventing practical use of these codes. Part 2 will consider whether the codes can be (or need to be) made to talk to each other and integrated into a whole.« less

Feeding differently processed soya bean. Part 2. An assessment of haematological responses in the chicken.

PubMed

Aletor, V A; Egberongbe, O

1992-01-01

The use of differently processed soya bean as a major source of dietary protein was evaluated in a haematological study using broiler chickens in which groundnut cake (GNC), raw soya bean (RSB), roasted soya bean (RtSB), cooked soya bean (CSB) and soya bean oil cake (SBC) were fed on equi-protein basis. The results showed that: 1. Red blood cell (RBC) count and haemoglobin content of blood significantly (P less than 0.05) increased in chicks fed RSB relative to the other soya bean diets. Feeding differently processed soya bean significantly (P less than 0.05) influenced mean cell haemoglobin (MCH) and mean corpuscular volume (MCV) while the mean corpuscular haemoglobin concentration (MCHC) was not significantly influenced. 2. Both the total white blood cell (WBC) count and the monocytes were significantly (P less than 0.05) influenced by the dietary treatments. Chicks fed processed soya bean generally had higher number of monocytes. 3. Physical properties determined were specific gravity and erythrocyte sedimentation rate. The latter was significantly (P less than 0.05) lower in all the processed soya bean-fed chicks. 4. Minerals determined in blood were Na, K, Ca, Mg, Fe, Cu and P. Of all these, chicks fed RSB had significantly (P less than 0.01) lower levels of blood Mg and marked decrease in Ca.

Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells

PubMed Central

1988-01-01

To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold. Incorporation of labeled subunits into the cytoskeleton of neurites was observed within minutes after microinjection. Serial electron microscopic reconstruction revealed that existing MTs in PC12 neurites incorporated labeled subunits mainly at their distal ends and the elongation rate of labeled segments was estimated to be less than 0.3 micron/min. Overall organization of MTs in the nerve cells was different from that in undifferentiated cells such as fibroblasts. Namely, we have not identified any MT-organizing centers from which labeled MTs are emanating in the cell bodies of the injected cells. Stereo electron microscopy revealed that some fully labeled segments seemed to start in the close vicinity of electron dense material within the neurites. This suggests new nucleation off some structures in the neurites. We have also studied the overall pattern of the incorporation of labeled subunits which extended progressively from the proximal part of the neurites toward their tips. To characterize the mechanism of tubulin incorporation, we have measured mean density of gold labeling per unit length of labeled segments at different parts of the neurites. The results indicate access of free tubulin subunits into the neurites and local incorporation into the neurite cytoskeleton. Our results lead to the conclusion that MTs are not static polymers but dynamic structures that continue to elongate even within the differentiated nerve cell processes. PMID:3047145

Non-canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development.

PubMed

Liu, Katherine; Wong, Elaine W; Schutzer, Steven E; Connell, Nancy D; Upadhyay, Alok; Bryan, Margarette; Rameshwar, Pranela

2009-08-01

Anthrax receptor (ATR) shares similarities with molecules relevant to haematopoiesis. This suggests that anthrax proteins might bind to these mimicking molecules and exert non-specific haematopoietic effects. The haematopoietic system is the site of immune cell development in the adult. As such, ATR ligand, protective antigen (PA) and the other anthrax proteins, lethal factor, edema factor, could be significant to haematopoietic responses against Bacillus anthracis infection. Because haematopoiesis is the process of immune cell development, effects by anthrax proteins could be relevant to vaccine development. Here, we report on effects of anthrax proteins and toxins on early and late haematopoiesis. Flow cytometry shows binding of PA to haematopoietic cells. This binding might be partly specific because flow cytometry and Western blots demonstrate the presence of ATR1 on haematopoietic cell subsets and the supporting stromal cells. Functional studies with long-term initiating cell and clonogenic assays determined haematopoietic suppression by anthrax toxins and stimulation by monomeric proteins. The suppressive effects were not attributed to cell death, but partly through the induction of haematopoietic suppressors, interleukin (IL)-10 and CCL3 (MIP-1alpha). In summary, anthrax proteins affect immune cell development by effects on haematopoiesis. The type of effect, stimulation or suppression, depend on whether the stimulator is a toxin or monomeric protein. The studies show effects of anthrax proteins beginning at the early stage of haematopoiesis, and also show secondary mediators such as IL-10 and CCL3. The roles of other cytokines and additional ATR are yet to be investigated.

From inanimate matter to living systems

NASA Technical Reports Server (NTRS)

Fox, S. W.

1980-01-01

Since the early part of this century, the Genesis account of the origin and evolution of life has been explained as an extrapolation of astronomical and geochemical processes. The essence of the answer to date is a protoreproductive protocell of much biochemical and cytophysical competance. The processes of its origin, molecular ordering, and its functions are described. A crucial understanding is that of the nonrandomness of evolutionary processes at all stages (with perhaps a minor statistical component). In this way, evolution conflicts with statistical randomness; the latter is a favorite assumption of both scientific and creationistic critics of the proteinoid theory. The principle contribution of the proteinoid theory to the understanding of general biology is to particularize the view that evolutionary direction is rooted in the shapes of molecules, in stereochemistry. After molecules of the right kind first assembled to protocells, life in its various stages of evolution was an inevitable consequence. It is molecules that continue to assemble as part of living process and, in the role of enzymes, continue to direct life cycle of the cell.

Ikaros promotes rearrangement of TCR α genes in an Ikaros null thymoma cell line.

PubMed

Collins, Bernard; Clambey, Eric T; Scott-Browne, James; White, Janice; Marrack, Philippa; Hagman, James; Kappler, John W

2013-02-01

Ikaros is important in the development and maintenance of the lymphoid system, functioning in part by associating with chromatin-remodeling complexes. We have studied the functions of Ikaros in the transition from pre-T cell to the CD4(+) CD8(+) thymocyte using an Ikaros null CD4(-) CD8(-) mouse thymoma cell line (JE131). We demonstrate that this cell line carries a single functional TCR β gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry nonfunctional rearrangements on both alleles of their TCR α loci. Retroviral reintroduction of Ikaros dramatically increased the rate of transcription in the α locus and TCR Vα/Jα recombination resulting in the appearance of many new αβTCR(+) cells. The process is RAG dependent, requires switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR α enhancer. Furthermore, knockdown of Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of TCR α rearrangement. Our data suggest that Ikaros controls Vα/Jα recombination in T cells by controlling access of the transcription and recombination machinery to the TCR α loci. The JE131 cell line should prove to be a very useful tool for studying the molecular details of this and other processes involved in the pre-T cell to αβTCR(+) CD4(+) CD8(+) thymocyte transition. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concise review: stem cell-derived erythrocytes as upcoming players in blood transfusion.

PubMed

Zeuner, Ann; Martelli, Fabrizio; Vaglio, Stefania; Federici, Giulia; Whitsett, Carolyn; Migliaccio, Anna Rita

2012-08-01

Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing knowledge of processes that govern erythropoiesis has been translated into efficient procedures to produce RBC ex vivo using primary hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells. Although in vitro-generated RBCs have recently entered clinical evaluation, several issues related to ex vivo RBC production are still under intense scrutiny: among those are the identification of stem cell sources more suitable for ex vivo RBC generation, the translation of RBC culture methods into clinical grade production processes, and the development of protocols to achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements. Copyright © 2012 AlphaMed Press.

The Reverse Transcription Inhibitor Abacavir Shows Anticancer Activity in Prostate Cancer Cell Lines

PubMed Central

Molinari, Agnese; Parisi, Chiara; Bozzuto, Giuseppina; Toccacieli, Laura; Formisano, Giuseppe; De Orsi, Daniela; Paradisi, Silvia; Grober, OlÌ Maria Victoria; Ravo, Maria; Weisz, Alessandro; Arcieri, Romano; Vella, Stefano; Gaudi, Simona

2010-01-01

Background Transposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines. Principal Findings ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. Conclusions Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications. PMID:21151977

Bortezomib: a novel therapy approved for multiple myeloma.

PubMed

Richardson, Paul G; Anderson, Kenneth C

2003-10-01

Cellular homeostasis requires routine degradation of key regulatory proteins, including tumor suppressor gene products, transcription factors, cell-cycle proteins and their inhibitors, as well as damaged and misfolded proteins. A critical part of this process is mediated by the 26S proteasome, a multi-subunit enzyme found in the nucleus and cytoplasm of all eukaryotic cells. Because of its essential role in many cellular processes controlling growth and survival, the proteasome has been identified as a potential target for cancer therapy. Drugs known to inhibit proteasome activity have been shown to induce cell-cycle arrest and programmed cell death (apoptosis). The impact of this finding is heightened by research showing that cancer cells are more sensitive to the proapoptotic effects of proteasome inhibition than normal cells. Preclinical evidence using bortezomib, the only proteasome inhibitor to enter clinical trials, suggests that proteasome inhibition may be effective in the treatment of hematologic and solid malignancies by promoting apoptosis, retarding angiogenesis, and inhibiting tumor cell adhesion and production of growth factors by acting on molecules such as nuclear factor-kappaB. Further preclinical evidence suggests that the antitumor effects of cytotoxic chemotherapy or radiotherapy may be enhanced by the addition of a proteasome inhibitor. Bortezomib was recently approved for the treatment of multiple myeloma. It is currently being investigated, both as a single agent and in combination, in phase I and II trials in a variety of tumor types.

FULL SCALE BIOREACTOR LANDFILL FOR CARBON SEQUESTRATION AND GREENHOUSE EMISSION CONTROL

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

Ramin Yazdani; Jeff Kieffer; Heather Akau

2003-12-01

The Yolo County Department of Planning and Public Works is constructing a full-scale bioreactor landfill as a part of the Environmental Protection Agency's (EPA) Project XL program to develop innovative approaches for carbon sequestration and greenhouse emission control. The overall objective is to manage landfill solid waste for rapid waste decomposition and maximum landfill gas generation and capture for carbon sequestration and greenhouse emission control. Waste decomposition is accelerated by improving conditions for either the aerobic or anaerobic biological processes and involves circulating controlled quantities of liquid (leachate, groundwater, gray water, etc.), and, in the aerobic process, large volumes ofmore » air. The first phase of the project entails the construction of a 12-acre module that contains a 6-acre anaerobic cell, a 3.5-acre anaerobic cell, and a 2.5-acre aerobic cell at the Yolo County Central Landfill near Davis, California. The cells are highly instrumented to monitor bioreactor performance. Liquid addition has commenced in the 3.5-acre anaerobic cell and the 6-acre anaerobic cell. Construction of the 2.5-acre aerobic cell and biofilter has been completed. The remaining task to be completed is to test the biofilter prior to operation, which is currently anticipated to begin in January 2004. The current project status and preliminary monitoring results are summarized in this report.« less

Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells.

PubMed

Tilaoui, Mounir; Ait Mouse, Hassan; Jaafari, Abdeslam; Zyad, Abdelmajid

2015-01-01

Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba. Essential oils were studied by gas chromatography coupled to mass spectrometry (GC-MS) and their antitumoral activity was tested against P815 mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the effect on normal human cells, oils were tested against peripheral blood mononuclear cells PBMCs. Essential oils from leaves and aerial parts (mixture of capitulum and leaves) were mainly composed by oxygenated sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained essentially monoterpenes (22.86%) and monocyclic monoterpenes (21.48%); esters constituted the major fraction (62.8%) of stem oil. Essential oils of different biological parts studied demonstrated a differential antiproliferative activity against P815 and BSR cancer cells; P815 cells are the most sensitive to the cytotoxic effect. Leaves and capitulum essential oils are more active than aerial parts. Interestingly, no cytotoxic effect of these essential oils was observed on peripheral blood mononuclear cells. Our results showed that the chemical composition variability of essential oils depends on the nature of botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that the differential cytotoxic effect depends not only on the essential oils concentration, but also on the target cells and the botanical parts of essential oils used.

INTEGRATED GASIFICATION COMBINED CYCLE PROJECT 2 MW FUEL CELL DEMONSTRATION

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

FuelCell Energy

2005-05-16

With about 50% of power generation in the United States derived from coal and projections indicating that coal will continue to be the primary fuel for power generation in the next two decades, the Department of Energy (DOE) Clean Coal Technology Demonstration Program (CCTDP) has been conducted since 1985 to develop innovative, environmentally friendly processes for the world energy market place. The 2 MW Fuel Cell Demonstration was part of the Kentucky Pioneer Energy (KPE) Integrated Gasification Combined Cycle (IGCC) project selected by DOE under Round Five of the Clean Coal Technology Demonstration Program. The participant in the CCTDP Vmore » Project was Kentucky Pioneer Energy for the IGCC plant. FuelCell Energy, Inc. (FCE), under subcontract to KPE, was responsible for the design, construction and operation of the 2 MW fuel cell power plant. Duke Fluor Daniel provided engineering design and procurement support for the balance-of-plant skids. Colt Engineering Corporation provided engineering design, fabrication and procurement of the syngas processing skids. Jacobs Applied Technology provided the fabrication of the fuel cell module vessels. Wabash River Energy Ltd (WREL) provided the test site. The 2 MW fuel cell power plant utilizes FuelCell Energy's Direct Fuel Cell (DFC) technology, which is based on the internally reforming carbonate fuel cell. This plant is capable of operating on coal-derived syngas as well as natural gas. Prior testing (1992) of a subscale 20 kW carbonate fuel cell stack at the Louisiana Gasification Technology Inc. (LGTI) site using the Dow/Destec gasification plant indicated that operation on coal derived gas provided normal performance and stable operation. Duke Fluor Daniel and FuelCell Energy developed a commercial plant design for the 2 MW fuel cell. The plant was designed to be modular, factory assembled and truck shippable to the site. Five balance-of-plant skids incorporating fuel processing, anode gas oxidation, heat recovery, water treatment/instrument air, and power conditioning/controls were built and shipped to the site. The two fuel cell modules, each rated at 1 MW on natural gas, were fabricated by FuelCell Energy in its Torrington, CT manufacturing facility. The fuel cell modules were conditioned and tested at FuelCell Energy in Danbury and shipped to the site. Installation of the power plant and connection to all required utilities and syngas was completed. Pre-operation checkout of the entire power plant was conducted and the plant was ready to operate in July 2004. However, fuel gas (natural gas or syngas) was not available at the WREL site due to technical difficulties with the gasifier and other issues. The fuel cell power plant was therefore not operated, and subsequently removed by October of 2005. The WREL fuel cell site was restored to the satisfaction of WREL. FuelCell Energy continues to market carbonate fuel cells for natural gas and digester gas applications. A fuel cell/turbine hybrid is being developed and tested that provides higher efficiency with potential to reach the DOE goal of 60% HHV on coal gas. A system study was conducted for a 40 MW direct fuel cell/turbine hybrid (DFC/T) with potential for future coal gas applications. In addition, FCE is developing Solid Oxide Fuel Cell (SOFC) power plants with Versa Power Systems (VPS) as part of the Solid State Energy Conversion Alliance (SECA) program and has an on-going program for co-production of hydrogen. Future development in these technologies can lead to future coal gas fuel cell applications.« less

Engineered decellularized matrices to instruct bone regeneration processes.

PubMed

Papadimitropoulos, Adam; Scotti, Celeste; Bourgine, Paul; Scherberich, Arnaud; Martin, Ivan

2015-01-01

Despite the significant progress in the field of bone tissue engineering, cell-based products have not yet reached the stage of clinical adoption. This is due to the uncertain advantages from the standard-of-care, combined with challenging cost-and regulatory-related issues. Novel therapeutic approaches could be based on exploitation of the intrinsic regenerative capacity of bone tissue, provided the development of a deeper understanding of its healing mechanisms. While it is well-established that endogenous progenitors can be activated toward bone formation by overdoses of single morphogens, the challenge to stimulate the healing processes by coordinated and controlled stimulation of specific cell populations remains open. Here, we review the recent approaches to generate osteoinductive materials based on the use of decellularized extracellular matrices (ECM) as reservoirs of multiple factors presented at physiological doses and through the appropriate ligands. We then propose the generation of customized engineered and decellularized ECM (i) as a tool to better understand the processes of bone regeneration and (ii) as safe and effective "off-the-shelf" bone grafts for clinical use. This article is part of a Special Issue entitled Stem Cells and Bone. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

PubMed Central

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

Polycrystalline silicon material availability and market pricing outlook for 1980 through 1988

NASA Technical Reports Server (NTRS)

Costogue, E. N.; Ferber, R. R.

1984-01-01

The results of the second JPL update to an original report to assess the availability and prices of polycrystalline Si for solar cells in the 1983-88 interval are reported. It is noted that the demand for poly-Si for solar cells competes with the demand for the same material for semiconductors, although the solar cell industry can use material rejected from the semiconductor industry. A sufficient supply is projected for the 6 yr period, rising from 3224 metric tons to 10,220 metric tons in 1988, with prices dropping from the 1980 level of $140/kg to $25/kg. The price reduction and improved production are noted to be due in large part to DOE efforts at defining lower-cost production processes.

Operating a redox flow battery with a negative electrolyte imbalance

DOEpatents

Pham, Quoc; Chang, On; Durairaj, Sumitha

2015-03-31

Loss of flow battery electrode catalyst layers during self-discharge or charge reversal may be prevented by establishing and maintaining a negative electrolyte imbalance during at least parts of a flow battery's operation. Negative imbalance may be established and/or maintained actively, passively or both. Actively establishing a negative imbalance may involve detecting an imbalance that is less negative than a desired threshold, and processing one or both electrolytes until the imbalance reaches a desired negative level. Negative imbalance may be effectively established and maintained passively within a cell by constructing a cell with a negative electrode chamber that is larger than the cell's positive electrode chamber, thereby providing a larger quantity of negative electrolyte for reaction with positive electrolyte.

De novo Transcriptome Assembly of Floral Buds of Pineapple and Identification of Differentially Expressed Genes in Response to Ethephon Induction

PubMed Central

Liu, Chuan-He; Fan, Chao

2016-01-01

A remarkable characteristic of pineapple is its ability to undergo floral induction in response to external ethylene stimulation. However, little information is available regarding the molecular mechanism underlying this process. In this study, the differentially expressed genes (DEGs) in plants exposed to 1.80 mL·L−1 (T1) or 2.40 mL·L−1 ethephon (T2) compared with Ct plants (control, cleaning water) were identified using RNA-seq and gene expression profiling. Illumina sequencing generated 65,825,224 high-quality reads that were assembled into 129,594 unigenes with an average sequence length of 1173 bp. Of these unigenes, 24,775 were assigned to specific KEGG pathways, of which metabolic pathways and biosynthesis of secondary metabolites were the most highly represented. Gene Ontology (GO) analysis of the annotated unigenes revealed that the majority were involved in metabolic and cellular processes, cell and cell part, catalytic activity and binding. Gene expression profiling analysis revealed 3788, 3062, and 758 DEGs in the comparisons of T1 with Ct, T2 with Ct, and T2 with T1, respectively. GO analysis indicated that these DEGs were predominantly annotated to metabolic and cellular processes, cell and cell part, catalytic activity, and binding. KEGG pathway analysis revealed the enrichment of several important pathways among the DEGs, including metabolic pathways, biosynthesis of secondary metabolites and plant hormone signal transduction. Thirteen DEGs were identified as candidate genes associated with the process of floral induction by ethephon, including three ERF-like genes, one ETR-like gene, one LTI-like gene, one FT-like gene, one VRN1-like gene, three FRI-like genes, one AP1-like gene, one CAL-like gene, and one AG-like gene. qPCR analysis indicated that the changes in the expression of these 13 candidate genes were consistent with the alterations in the corresponding RPKM values, confirming the accuracy and credibility of the RNA-seq and gene expression profiling results. Ethephon-mediated induction likely mimics the process of vernalization in the floral transition in pineapple by increasing LTI, FT, and VRN1 expression and promoting the up-regulation of floral meristem identity genes involved in flower development. The candidate genes screened can be used in investigations of the molecular mechanisms of the flowering pathway and of various other biological mechanisms in pineapple. PMID:26955375

Tribbles role in reproduction.

PubMed

Basatvat, Shaghayegh; Carter, Deborah Angela Louise; Kiss-Toth, Endre; Fazeli, Alireza

2015-10-01

Tribbles (TRIB) proteins, a family of evolutionary conserved psuedokinase proteins, modulate various signalling pathways within the cell. The regulatory roles of TRIB make them an important part of a number of biological processes ranging from cell proliferation to metabolism, immunity, inflammation and carcinogenesis. Innate immune system plays a pivotal role during the regulation of reproductive processes that allows successful creation of an offspring. Its involvement initiates from fertilization of the oocyte by spermatozoon and lasts throughout early embryonic development, pregnancy and labour. Therefore, there is a close cooperation between the reproductive system and the innate immune system. Evidence from our lab has demonstrated that improper activation of the innate immune system can reduce embryo implantation, thus leading to infertility. Therefore, control mechanisms regulating the innate immune system function can be critical for successful reproductive events. © 2015 Authors; published by Portland Press Limited.

Entry inhibitors in the treatment of HIV-1 infection.

PubMed

Tilton, John C; Doms, Robert W

2010-01-01

Infection of target cells by HIV is a complex, multi-stage process involving attachment to host cells and CD4 binding, coreceptor binding, and membrane fusion. Drugs that block HIV entry are collectively known as entry inhibitors, but comprise a complex group of drugs with multiple mechanisms of action depending on the stage of the entry process at which they act. Two entry inhibitors, maraviroc and enfuvirtide, have been approved for the treatment of HIV-1 infection, and a number of agents are in development. This review covers the entry inhibitors and their use in the management of HIV-1 infection. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

Combining Laboratory Experiments with Digital Tools to Do Scientific Inquiry

ERIC Educational Resources Information Center

Kluge, Anders

2014-01-01

This qualitative study investigates the gap between a lab experiment and theory of science. Two groups of 4 students in 2 different classes in 11th grade (15-16 years old) are followed as they process results and experiences from a lab experiment using a digital environment. The experiment is as a part of a larger project about genes and cells,…

Flexible manufacturing of aircraft engine parts

NASA Astrophysics Data System (ADS)

Hassan, Ossama M.; Jenkins, Douglas M.

1992-06-01

GE Aircraft Engines, a major supplier of jet engines for commercial and military aircraft, has developed a fully integrated manufacturing facility to produce aircraft engine components in flexible manufacturing cells. This paper discusses many aspects of the implementation including process technologies, material handling, software control system architecture, socio-technical systems and lessons learned. Emphasis is placed on the appropriate use of automation in a flexible manufacturing system.

Fiber-Coupled Acousto-Optical-Filter Spectrometer

NASA Technical Reports Server (NTRS)

Levin, Kenneth H.; Li, Frank Yanan

1993-01-01

Fiber-coupled acousto-optical-filter spectrometer steps rapidly through commanded sequence of wavelengths. Sample cell located remotely from monochromator and associated electronic circuitry, connected to them with optical fibers. Optical-fiber coupling makes possible to monitor samples in remote, hazardous, or confined locations. Advantages include compactness, speed, and no moving parts. Potential applications include control of chemical processes, medical diagnoses, spectral imaging, and sampling of atmospheres.

Nanoimprinted backside reflectors for a-Si:H thin-film solar cells: critical role of absorber front textures.

PubMed

Tsao, Yao-Chung; Fisker, Christian; Pedersen, Thomas Garm

2014-05-05

The development of optimal backside reflectors (BSRs) is crucial for future low cost and high efficiency silicon (Si) thin-film solar cells. In this work, nanostructured polymer substrates with aluminum coatings intended as BSRs were produced by positive and negative nanoimprint lithography (NIL) techniques, and hydrogenated amorphous silicon (a-Si:H) was deposited hereon as absorbing layers. The relationship between optical properties and geometry of front textures was studied by combining experimental reflectance spectra and theoretical simulations. It was found that a significant height variation on front textures plays a critical role for light-trapping enhancement in solar cell applications. As a part of sample preparation, a transfer NIL process was developed to overcome the problem of low heat deflection temperature of polymer substrates during solar cell fabrication.

Monitoring developmental force distributions in reconstituted embryonic epithelia.

PubMed

Przybyla, L; Lakins, J N; Sunyer, R; Trepat, X; Weaver, V M

2016-02-01

The way cells are organized within a tissue dictates how they sense and respond to extracellular signals, as cues are received and interpreted based on expression and organization of receptors, downstream signaling proteins, and transcription factors. Part of this microenvironmental context is the result of forces acting on the cell, including forces from other cells or from the cellular substrate or basement membrane. However, measuring forces exerted on and by cells is difficult, particularly in an in vivo context, and interpreting how forces affect downstream cellular processes poses an even greater challenge. Here, we present a simple method for monitoring and analyzing forces generated from cell collectives. We demonstrate the ability to generate traction force data from human embryonic stem cells grown in large organized epithelial sheets to determine the magnitude and organization of cell-ECM and cell-cell forces within a self-renewing colony. We show that this method can be used to measure forces in a dynamic hESC system and demonstrate the ability to map intracolony protein localization to force organization. Copyright © 2015 Elsevier Inc. All rights reserved.