bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of CD8+ T Cell Memory Using Bcl-2 as a Marker
Authors: Dunkle Alexis , Dzhagalov Ivan , Gordy Claire , He You-Wen 
Published: December 2012

Abstract
The processes that regulate T cell memory generation are important for therapeutic design and the immune response to disease. However, what allows a subset of effector T cells to survive the contraction period to become memory cells is incompletely understood. The Bcl-2 family is critical for T cell survival, and Bcl-2 has been proposed to be important for the survival of memory cells. However, previous studies have relied on double-knockout models, potentially skewing the role of Bcl-2, and the use of Bcl-2 as a marker in adoptive transfer experiments, a method required to confirm the memory potential of cell subsets, has not been possible because of the intracellular localization of the protein. In this study, we present a novel Bcl-2 reporter mouse model and, to our knowledge, show for the first time that a distinct subset of effector T cells, and also a subset within the CD127hiKLRG1lo memory precursor effector cell population, retains high Bcl-2 expression at the peak of the CD8+ T cell response to Listeria monocytogenes. Furthermore, we show that Bcl-2 correlates with memory potential in adoptive transfer experiments using both total responding CD8+ T cells and memory precursor effector cells. These results show that even within the memory precursor effector cell population, Bcl-2 confers a survival advantage in a subset of effector CD8+ T cells that allows differentiation into memory cells and cement Bcl-2 as a critical factor for T cell memory.
Mnk1 and 2 Are Dispensable for T Cell Development and Activation but Important for the Pathogenesis of Experimental Autoimmune Encephalomyelitis
Authors: Gorentla Balachandra K. , Krishna Sruti , Shin Jinwook , Inoue Makoto , Shinohara Mari L. , Grayson Jason M. , Fukunaga Rikiro , Zhong Xiao-Ping 
Published: December 2012

Abstract
T cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5′ cap structure of mRNA and is critical for cap-dependent translational initiation. It has been hypothesized that MAPK-interacting kinase 1 and 2 (Mnk1/2) promote cap-dependent translation by phosphorylating eIF4E at serine 209 (S209). Pharmacologic studies using inhibitors have suggested that Mnk1/2 have important roles in T cells. However, genetic evidence supporting such conclusions is lacking. Moreover, the signaling pathways that regulate Mnk1/2 in T cells remain unclear. We demonstrate that TCR engagement activates Mnk1/2 in primary T cells. Such activation is dependent on Ras-Erk1/2 signaling and is inhibited by diacylglycerol kinases α and ζ. Mnk1/2 double deficiency in mice abolishes TCR-induced eIF4E S209 phosphorylation, indicating their absolute requirement for eIF4E S209 phosphorylation. However, Mnk1/2 double deficiency does not affect the development of conventional αβ T cells, regulatory T cells, or NKT cells. Furthermore, T cell activation, in vivo primary and memory CD8 T cell responses to microbial infection, and NKT cell cytokine production were not obviously altered by Mnk1/2 deficiency. Although Mnk1/2 deficiency causes decreased IL-17 and IFN-γ production by CD4 T cells following immunization of mice with myelin oligodendrocyte glycoprotein peptide in complete Freund’s adjuvant, correlating with milder experimental autoimmune encephalomyelitis scores, it does not affect Th cell differentiation in vitro. Together, these data suggest that Mnk1/2 has a minimal role in T cell development and activation but may regulate non–T cell lineages to control Th1 and Th17 differentiation in vivo.
The Receptor for Advanced Glycation End Products Promotes Pancreatic Carcinogenesis and Accumulation of Myeloid-Derived Suppressor Cells
Authors: Vernon Philip J. , Loux Tara J. , Schapiro Nicole E. , Kang Rui , Muthuswamy Ravi , Kalinski Pawel , Tang Daolin , Lotze Michael T. , Zeh Herbert J. 
Published: December 2012

AbstractPancreatic ductal adenocarcinoma (PDA) has an aggressive natural history and is resistant to therapy. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor for many damage-associated molecular pattern molecules. RAGE is overexpressed in both human and murine models of PDA as well as most advanced epithelial neoplasms. The immunosuppressive nature of the PDA microenvironment is facilitated, in part, by the accumulation of regulatory immune cell infiltrates such as myeloid-derived suppressor cells (MDSCs). To study the role of RAGE expression in the setting of mutant Ras-promoted pancreatic carcinogenesis (KC), a triple-transgenic model of spontaneous murine PDA in a RAGE-null background (KCR) was generated. KCR mice had markedly delayed pancreatic carcinogenesis and a significant diminution of MDSCs compared with KC mice at comparable time points postweaning. Although RAGE was not required for the development or suppressor activity of MDSCs, its absence was associated with temporally limited pancreatic neoplasia and altered phenotype and function of the myeloid cells. In lieu of MDSCs, KCR animals at comparable time points exhibited mature CD11b+Gr1−F4/80+ cells that were not immunosuppressive in vitro. KCR mice also maintained a significantly less suppressive milieu evidenced by marked decreases in CCL22 in relation to CXCL10 and diminished serum levels of IL-6.
An Organotypic Coculture Model Supporting Proliferation and Differentiation of Medullary Thymic Epithelial Cells and Promiscuous Gene Expression
Authors: Pinto Sheena , Schmidt Katrin , Egle Stefanie , Stark Hans-Jürgen , Boukamp Petra , Kyewski Bruno 
Published: December 2012

Abstract
Understanding intrathymic T cell differentiation has been greatly aided by the development of various reductionist in vitro models that mimic certain steps/microenvironments of this complex process. Most models focused on the faithful in vitro restoration of T cell differentiation and selection. In contrast, suitable in vitro models emulating the developmental pathways of the two major thymic epithelial cell lineages—cortical thymic epithelial cells and medullary thymic epithelial cells (mTECs)—are yet to be developed. In this regard, lack of an in vitro model mimicking the developmental biology of the mTEC lineage has hampered the molecular analysis of the so-called “promiscuous expression” of tissue-restricted genes, a key property of terminally differentiated mTECs. Based on the close biological relationship between the skin and thymus epithelial cell compartments, we adapted a three-dimensional organotypic coculture model, originally developed to provide a bona fide in vitro dermal equivalent, for the culture of isolated mTECs. This three-dimensional model preserves key features of mTECs: proliferation and terminal differentiation of CD80lo, Aire− mTECs into CD80hi, Aire+ mTECs; responsiveness to RANKL; and sustained expression of FoxN1, Aire, and tissue-restricted genes in CD80hi mTECs. This in vitro culture model should facilitate the identification of molecular components and pathways involved in mTEC differentiation in general and in promiscuous gene expression in particular.
Identification of SERPINB1 As a Physiological Inhibitor of Human Granzyme H
Authors: Wang Li , Li Qian , Wu Lianfeng , Liu Shengwu , Zhang Yong , Yang Xuan , Zhu Pingping , Zhang Honglian , Zhang Kai , Lou Jizhong , Liu Pingsheng , Tong Liang , Sun Fei , Fan Zusen 
Published: December 2012

Abstract
The granzyme/perforin pathway is a major mechanism for cytotoxic lymphocytes to eliminate virus-infected and tumor cells. The balance between activation and inhibition of the proteolytic cascade must be tightly controlled to avoid self damage. Granzyme H (GzmH) is constitutively expressed in NK cells and induces target cell death; however, how GzmH activity is regulated remains elusive. We reported earlier the crystal structures of inactive D102N-GzmH alone and in complex with its synthetic substrate and inhibitor, as well as defined the mechanisms of substrate recognition and enzymatic activation. In this study, we identified SERPINB1 as a potent intracellular inhibitor for GzmH. Upon cleavage of the reactive center loop at Phe343, SERPINB1 forms an SDS-stable covalent complex with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell–mediated cytotoxicity. We determined the crystal structures of active GzmH and SERPINB1 (LM-DD mutant) in the native conformation to 3.0- and 2.9-Å resolution, respectively. Molecular modeling reveals the possible conformational changes in GzmH for the suicide inhibition. Our findings provide new insights into the inhibitory mechanism of SERPINB1 against human GzmH.
The Assessment of Fetal Neurobehavior with Four-dimensional Ultrasound: The Kurjak Antenatal Neurodevelopmental Test
Authors: Antsaklis Aris 
Published: December 2012

ABSTRACT
Fetal neurology is an evolving field in prenatal diagnosis and fetal medicine with great interest. The identification and diagnosis of brain damage prenatally has been a great challenge in obstetrics for many years and early identification of this damage would have implications on the perinatal management and is of great importance in cases of medical litigation. Defining normal and abnormal fetal neurological function in utero in order to better predict antenatally which fetuses are at risk for adverse neurological outcome still is under investigation. Several attempts have been made in the past to form a system that could detect fetuses with compromised central nervous system (CNS) function or brain impairement. Assessment of fetal behavior gave a promising opportunity to understand the hidden function of the developmental pathway of the fetal CNS. The assessment of normal neurobehavioral development by fourdimensional (4D) ultrasound gave the opportunity to investigate functional characteristics of the fetus that could predict neurological developmental dysfunction. These series of studies lead to the formation of Kurjak's antenatal neurodevelopmental test (KANET). KANET combines the assessment of fetal behavior, general movements and three out of four signs that have been postnatally considered as symptoms of possible neurodevelopmental impairment (neurological thumb, overlapping sutures and small head circumference). Assessment of fetal behavior by 4D ultrasound and application of KANET scoring test has been recently published in several journals and summarized results are presented in this review

How to cite this article
Antsaklis P, Antsaklis A. The Assessment of Fetal Neurobehavior with Four-dimensional Ultrasound: The Kurjak Antenatal Neurodevelopmental Test. Donald School J Ultrasound Obstet Gynecol 2012;6(4):362-375.
Maternal-Fetal Bonding: Ultrasound Imaging's Role in enhancing This Important Relationship
Authors: Appleton Kallie , Atluru Aparna 
Published: December 2012

ABSTRACT
New technology in ultrasound imaging is allowing women to view more visually precise images of their fetuses than ever before. Maternal-fetal bonding describes the attachment interaction that forms between a mother and her unborn child. Ultrasound diagnosis modalities including two-dimensional (2D), three-dimensional (3D) and four-dimensional (4D) may create differences in the amount of maternal-fetal bonding, depending on the modality used. When relevant literature was reviewed on this topic, no significant difference between maternal-fetal bonding was found when comparing 2D vs 3D vs 4D ultrasound. However, certain measures such as a perceived feeling of closeness to the baby were higher with 3D and 4D ultrasounds as compared with 2D ultrasound. Further exploration is needed to ascertain whether different ultrasound modalities have an effect on maternal-fetal bonding in multigestational pregnancies, pregnancies in which there is fetal demise, and to overall examine the effects of using ultrasound for nonmedical ‘entertainment’ purposes by prospective mothers.

How to cite this article
Atluru A, Appleton K, Kupesic Plavsic S. Maternal-Fetal Bonding: Ultrasound Imaging's Role in enhancing This Important Relationship. Donald School J Ultrasound Obstet Gynecol 2012;6(4):408-411.
Influence of Chitosan Concentration on Cell Viability and Proliferation in Vitro by Changing Film Topography
Authors: Martín-López Eduardo , Nieto-Díaz Manuel , Nieto-Sampedro Manuel 
Published: December 2012

Purpose Chitosan is a natural polysaccharide which can form gels and scaffolds that support its use as a biomaterial in various tissue engineering applications. A useful feature of chitosan polymer is that you can manipulate its properties easily. Thus, in this work we studied the effect of varying chitosan concentration in the topography and the biological properties of the chitosan films, as well as the effects in the structure of 3D gels in order to be used as nerve bridges. Methods Analysis of film topographies were addressed by swelling test and atomic force microscopy (AFM). In vitro biological properties were assessed through MTT viability assays on cultures of blood-brain barrier forming endothelial (bEnd5), glioma (C6) and postmitotic neuron (NGF-differentiated PC12) cell lines. The structure of tridimensional gels was studied by environmental scanning electron microscopy. Results Topography of 1% chitosan films showed a AFM profile with higher nano-roughness profile than that observed in 2% films, which was smoother. Moreover, swelling rate was not affected. Topography changes affected cell viability as shown by the MTT assays. Our results showed that 2% chitosan films promoted higher proliferation and viability of C6 and PC12 respectively than 1% films. Conversely, neither 1% nor 2% films promoted viability of bEnd5 cells. In order to establish the feasibility of both type of chitosan solutions as nerve bridges, we constructed 3D gels by alkaline precipitation. Resulting gels showed that only 2% gels were rigid enough to be effectively used as nerve bridges. Conclusions These results establish that changes in chitosan concentration affects the polymer surface topography, which has a direct effect in the growing cell behavior. Additionally, higher concentration of chitosan gels are required to be used in neural tissue engineering.
Lesotho's Minimum PMTCT Package: lessons learned for combating vertical HIV transmission using co‐packaged medicines
Authors: McDougal Lotus , Moteetee Mpolai M , Mohai Florence , Mphale Malisebo , Mahanty Binod , Motaung Blandinah , Ankrah Victor , Reynolds Makaria , Legins Kenneth , Tiam Appolinaire , Luo Chewe , McClure Craig , Binkin Nancy 
Published: December 2012

IntroductionMother‐to‐child transmission of HIV can be reduced to<5% with appropriate antiretroviral medications. Such reductions depend on multiple health system encounters during antenatal care (ANC), delivery and breastfeeding; in countries with limited access to care, transmission remains high. In Lesotho, where 28% of women attending ANC are HIV positive but where geographic and other factors limit access to ANC and facility deliveries, a Minimum PMTCT Package was launched in 2007 as an alternative to the existing facility‐based approach. Distributed at the first ANC visit, it packaged together all necessary pregnancy, delivery and early postnatal antiretroviral medications for mother and infant.MethodsTo examine the availability, feasibility, acceptability and possible negative consequences of the Minimum PMTCT Package, data from a 2009 qualitative and quantitative study and a 2010 facility assessment were used. To examine the effects on ANC and facility‐based delivery rates, a difference‐in‐differences analytic approach was applied to 2009 Demographic and Health Survey data for HIV‐tested women who gave birth before and after Minimum PMTCT Package implementation.ResultsThe Minimum PMTCT Package was feasible and acceptable to providers and clients. Problems with test kit and medicine stock‐outs occurred, and 46% of women did not receive the Minimum PMTCT Package until at least their second ANC visit. Providing adequate instruction on the use of multiple medications represented a challenge. The proportion of HIV‐positive women delivering in facilities declined after Minimum PMTCT Package implementation, although it increased among HIV‐negative women (difference‐in‐differences=14.5%, p=0.05). The mean number of ANC visits declined more among HIV‐positive women than among HIV‐negative women after implementation, though the difference was not statistically significant (p=0.09). Changes in the percentage of women receiving≥4 ANC visits did not differ between the two groups.ConclusionsIf supply issues can be resolved and adequate client educational materials provided, take‐away co‐packages have the potential to increase access to PMTCT commodities in countries where women have limited access to health services. However, efforts must be made to carefully monitor potential changes in ANC visits and facility deliveries, and further evaluation of adherence, safety and effectiveness are needed.
A new command governor architecture for transient response shaping
Authors: Yucelen Tansel , Johnson Eric 
Published: December 2012

SUMMARYIn this paper, we develop a control framework for stabilization and command following of nonlinear uncertain dynamical systems. The proposed methodology consists of a new command governor architecture and an adaptive controller. The command governor is a dynamical system that adjusts the trajectory of a given command to follow an ideal reference system capturing a desired closed‐loop dynamical system behavior in transient time. Specifically, we show that the controlled nonlinear uncertain dynamical system can approach the ideal reference system by choosing the design parameter of the command governor. In addition, an adaptive element is used to asymptotically assure that the error between the controlled nonlinear uncertain dynamical system and the ideal reference system is reduced in long term. Therefore, the proposed methodology not only has closed‐loop transient and steady‐state performance guarantees but can also shape the transient response by adjusting the trajectory of the given command with the command governor. We highlight that there exists a trade‐off between the adaptive controller's learning rate and the command governor's design parameter. This key feature of our framework allows rapid suppression of system uncertainties without resorting to a high learning rate in the adaptive controller. Furthermore, we discuss the robustness properties of the proposed approach with respect to high‐frequency dynamical system content such as measurement noise and ∕ or unmodeled dynamics. A numerical example is provided to demonstrate the efficacy of the proposed architecture. Copyright © 2012 John Wiley & Sons, Ltd.
Spin of a Nanotech Spin‐Off
Authors: Ozin Geoffrey A. 
Published: December 2012

AbstractInnovation in advanced technology often springs from ideas birthed in universities yet the attitudes of professors and their students towards entrepreneurship and their stance on the collision between fundamental research in the pursuit of knowledge and applied research directed to the creation of intellectual property, inventions, companies, jobs, products, and wealth, is not that well appreciated either inside or outside our universities. In this article I will explore this interesting issue and try to gain some insight into the challenges faced by professors confronted by the challenge of transforming basic science and engineering knowledge into products in the market place, using nanotechnology as a case study. While the specific focus of this article is on nanotechnology, more generic issues are also raised that relate to transformational business development and entrepreneurship in society and universities in a larger sense.
Core/Shell PbSe/PbS QDs TiO2 Heterojunction Solar Cell
Authors: Etgar Lioz , Yanover Diana , Čapek Richard Karel , Vaxenburg Roman , Xue Zhaosheng , Liu Bin , Nazeeruddin Mohammad Khaja , Lifshitz Efrat , Grätzel Michael 
Published: December 2012

AbstractQuasi type‐II PbSe/PbS quantum dots (QDs) are employed in a solid state high efficiency QD/TiO2 heterojunction solar cell. The QDs are deposited using layer‐by‐layer deposition on a half‐micrometer‐thick anatase TiO2 nanosheet film with (001) exposed facets. Theoretical calculations show that the carriers in PbSe/PbS quasi type‐II QDs are delocalized over the entire core/shell structure, which results in better QD film conductivity compared to PbSe QDs. Moreover, PbS shell permits better stability and facile electron injection from the QDs to the TiO2 nanosheets. To complete the electrical circuit of the solar cell, a Au film is evaporated as a back contact on top of the QDs. This PbSe/PbS QD/TiO2 heterojunction solar cell produces a light to electric power conversion efficiency (η) of 4% with short circuit photocurrent (Jsc) of 17.3 mA/cm2. This report demonstrates highly efficient core/shell near infrared QDs in a QD/TiO2 heterojunction solar cell.
Dendron‐Stabilized Liquid Crystalline Blue Phases with an Enlarged Controllable Range of the Photonic Band for Tunable Photonic Devices
Authors: Shibayama Seishi , Higuchi Hiroki , Okumura Yasushi , Kikuchi Hirotsugu 
Published: December 2012

AbstractLiquid crystalline blue phases (BPs) show excellent potential for application in tunable photonic devices because they possess the unique optical property that the selective 3D Bragg diffraction in a visible wavelength region can be continuously shifted using an electric field. A new approach to simultaneously extend the wavelength range of field‐induced Bragg diffraction shift and the temperature range of thermodynamically stable BPs is critically needed. Here, a new BP material system is shown using a dendron molecule to extend simultaneously the two BP ranges. One is the temperature range of thermodynamically stable BPs, which is expanded from 2.1 to 4.6 °C. The other is the reversible maximum shift range of Bragg wavelength on the electric field, which is extended from 85 to 109 nm. The physical mechanism of the dendron‐stabilizing effect in BPs is discussed in terms of elastic property and orientational order of liquid crystal molecules.
Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study
Authors: Chang Jing , Xu Xianghui , Li Haiping , Jian Yeting , Wang Gang , He Bin , Gu Zhongwei 
Published: December 2012

AbstractNovel nonviral gene vectors of alkaline amino acids such as arginine‐ (Arg), histidine‐ (His), and lysine‐ (Lys) modified chitosans (AAA‐CSs) are developed to simulate the components of viral envelopes to enhance transfection efficiency. The structures of the modified chitosans are characterized using 1H NMR spectroscopy. Acid‐base titration results indicate that the modified chitosans exhibit strong buffering capacity. The morphology of the AAA‐CSs/pDNA complexes is observed by use of transmission electron microscopy and atomic force microscopy. The complexes are spherical nanoparticles with a mean size around 100 nm. Zeta potential tests reveal that the complexes are positively charged and their zeta potentials vary from +0.1 to +19.5 mV. The MTT assay and agarose gel electrophoresis demonstrate that the AAA‐CSs are non‐cytotoxic and have excellent DNA condensation and protection abilities. Cellular uptake investigation of the AAA‐CSs/pDNA complexes demonstrates that Arg‐CS and His‐CS have better cellular internalization property than the unmodified chitosan. The in vitro gene transfection is evaluated in HEK293 and NIH3T3 cell lines and in vivo transfection is carried out in tibialis anterior muscles. The results reveal that the arginine‐modified chitosan could significantly enhance gene‐transfection efficiency both in vitro and in vivo.