bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantigen Immunization at Different Sites Reveals a Role for Anti-Inflammatory Effects of IFN-γ in Regulating Susceptibility to Experimental Autoimmune Encephalomyelitis
Authors: Pastor Silvia , Minguela Alfredo , Mi Wentao , Ward E. Sally
Published: April 2009

Experimental autoimmune encephalomyelitis is induced in B10.PL (H-2u) mice by immunization with the immunodominant N-terminal epitope of myelin basic protein, Ac1-9. In the present study, we show that the site of immunization impacts disease incidence and severity. This effect is more marked in female mice than in males. Although immunization in the flanks is effective in eliciting disease, delivery of Ag in the footpad and tailbase results in poor induction. Analyses of the immune responses in female mice following different immunization regimens indicates that resistance to disease is accompanied by higher levels of IFN-γ and CD11b+Gr-1int myeloid cells. Such myeloid cells are known to have a suppressive function, and consistent with this knowledge, blockade of IFN-γ results in increased disease activity and decreased levels of splenic CD11b+Gr-1int cells. Conversely, injection of adjuvants (CFA or Pam3CSK4) in the footpad decreases experimental autoimmune encephalomyelitis incidence and severity. Our study indicates that the site of immunization can impact the magnitude of the ensuing inflammatory response, and that at a certain threshold a protective, regulatory circuit can be elicited.
TLR Agonists Prevent the Establishment of Allogeneic Hematopoietic Chimerism in Mice Treated with Costimulation Blockade
Authors: Miller David M. , Thornley Thomas B. , Pearson Todd , Kruger Annie J. , Yamazaki Masahiro , Shultz Leonard D. , Welsh Raymond M. , Brehm Michael A. , Rossini Aldo A. , Greiner Dale L.
Published: April 2009

Activation of TLR4 by administration of LPS shortens the survival of skin allografts in mice treated with costimulation blockade through a CD8 T cell-dependent, MyD88-dependent, and type I IFN receptor-dependent pathway. The effect of TLR activation on the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade is not known. Using a costimulation blockade protocol based on a donor-specific transfusion (DST) and a short course of anti-CD154 mAb, we show that LPS administration at the time of DST matures host alloantigen-presenting dendritic cells, prevents the establishment of mixed allogeneic hematopoietic chimerism, and shortens survival of donor-specific skin allografts. LPS mediates its effects via a mechanism that involves both CD4+ and CD8+ T cells and results from signaling through either the MyD88 or the type I IFN receptor pathways. We also document that timing of LPS administration is critical, as injection of LPS 24 h before treatment with DST and anti-CD154 mAb does not prevent hematopoietic engraftment but administration the day after bone marrow transplantation does. We conclude that TLR4 activation prevents the induction of mixed allogeneic hematopoietic chimerism through type I IFN receptor and MyD88-dependent signaling, which leads to the up-regulation of costimulatory molecules on host APCs and the generation of alloreactive T cells. These data suggest that distinct but overlapping cellular and molecular mechanisms control the ability of TLR agonists to block tolerance induction to hematopoietic and skin allografts in mice treated with costimulation blockade.
Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreERT2
Authors: Higashi Atsuko Yoshioka , Ikawa Tomokatsu , Muramatsu Masamichi , Economides Aris N. , Niwa Akira , Okuda Tomohiko , Murphy Andrew J. , Rojas Jose , Heike Toshio , Nakahata Tatsutoshi , Kawamoto Hiroshi , Kita Toru , Yanagita Motoko
Published: April 2009

The CreERT2 for conditional gene inactivation has become increasingly used in reverse mouse genetics, which enables temporal regulation of Cre activity using a mutant estrogen binding domain (ERT2) to keep Cre inactive until the administration of tamoxifen. In this study, we present the severe toxicity of ubiquitously expressed CreERT2 in adult mice and embryos. The toxicity of Cre recombinase or CreERT2 in vitro or in vivo organisms are still less sufficiently recognized considering the common use of Cre/loxP system, though the toxicity might compromise the phenotypic analysis of the gene of interest. We analyzed two independent lines in which CreERT2 is knocked-in into the Rosa26 locus (R26CreERT2 mice), and both lines showed thymus atrophy, severe anemia, and illegitimate chromosomal rearrangement in hematopoietic cells after the administration of tamoxifen, and demonstrated complete recovery of hematological toxicity in adult mice. In the hematopoietic tissues in R26CreERT2 mice, reduced proliferation and increased apoptosis was observed after the administration of tamoxifen. Flow cytometric analysis revealed that CreERT2 toxicity affected several hematopoietic lineages, and that immature cells in these lineages tend to be more sensitive to the toxicity. In vitro culturing of hematopoietic cells from these mice further demonstrated the direct toxicity of CreERT2 on growth and differentiation of hematopoietic cells. We further demonstrated the cleavage of the putative cryptic/pseudo loxP site in the genome after the activation of CreERT2 in vivo. We discussed how to avoid the misinterpretation of the experimental results from potential toxic effects due to the activated CreERT2.
Molecular Dissection of Antibody Responses against Pneumococcal Surface Protein A: Evidence for Diverse DH-Less Heavy Chain Gene Usage and Avidity Maturation
Authors: Rohatgi Soma , Dutta Debjani , Tahir Suhail , Sehgal Devinder
Published: April 2009

Immunization of human volunteers with a single dose of pneumococcal surface protein A (PspA) stimulates broad cross-reactive Abs to heterologous PspA molecules that, when transferred, protect mice from fatal infection with Streptococcus pneumoniae. In this study, we report the molecular characterization of 36 mouse mAbs generated against the extracellular domain of PspA (PspA3–286) from strain R36A. Abs to PspA3–286 were encoded by diverse VH and Vκ families/genes. The H chain CDR3 and L chain CDR3 lengths were 3–13 (7.8 ± 0.5) and 8–9 (8.7 ± 0.2) codons, respectively. Unexpectedly, seven hybridomas expressed H chains that lack DH gene-derived amino acids. Nontemplate-encoded addition(s) were observed in the H chain expressed in six of these seven hybridomas; Palindromic addition(s) were absent. Absence of DH gene-derived amino acids did not prevent anti-PspA3–286 mAbs from attaining average relative avidity. Avidity maturation occurred during primary IgG anti-PspA3–286 polyclonal Ab response in PspA3–286- and R36A-immunized mice. Compared with PspA3–286-immunized mice, the relative avidity of the primary polyclonal IgG Abs was higher in R36A immunized mice on days 72, 86, and 100. Two pairs of clonally related hybridomas were observed. DH genes expressed in the majority (75.9%) of the hybridomas used reading frame 3. Analysis of replacement/silent mutation ratio in the CDR and framework regions provided evidence for Ag-driven selection in 11 mAbs. Based on epitope localization experiments, the mAbs were classified into 12 independent groups. ELISA additivity assay indicated that members within a group recognized topographically related epitopes. This study provides molecular insights into the biology of DH-less Abs.
Galectin-1 Tunes TCR Binding and Signal Transduction to Regulate CD8 Burst Size
Authors: Liu Scot D. , Tomassian Tamar , Bruhn Kevin W. , Miller Jeff F. , Poirier Françoise , Miceli M. Carrie
Published: April 2009

T cell burst size is regulated by the duration of TCR engagement and balanced control of Ag-induced activation, expansion, and apoptosis. We found that galectin-1-deficient CD8 T cells undergo greater cell division in response to TCR stimulation, with fewer dividing cells undergoing apoptosis. TCR-induced ERK signaling was sustained in activated galectin-1-deficient CD8 T cells and antagonized by recombinant galectin-1, indicating galectin-1 modulates TCR feed-forward/feedback loops involved in signal discrimination and procession. Furthermore, recombinant galectin-1 antagonized binding of agonist tetramers to the TCR on activated OT-1 T cells. Finally, galectin-1 produced by activated Ag-specific CD8 T cells negatively regulated burst size and TCR avidity in vivo. Therefore, galectin-1, inducibly expressed by activated CD8 T cells, functions as an autocrine negative regulator of peripheral CD8 T cell TCR binding, signal transduction, and burst size. Together with recent findings demonstrating that gal-1 promotes binding of agonist tetramers to the TCR of OT-1 thymocytes, these studies identify galectin-1 as a tuner of TCR binding, signaling, and functional fate determination that can differentially specify outcome, depending on the developmental and activation stage of the T cell.
Locally Administered TLR7 Agonists Drive Systemic Antitumor Immune Responses That Are Enhanced by Anti-CD40 Immunotherapy
Authors: Broomfield Steve A. , van der Most Robbert G. , Prosser Amy C. , Mahendran Sathish , Tovey Michael G. , Smyth Mark J. , Robinson Bruce W. S. , Currie Andrew J.
Published: April 2009

Topical application of tumors with the TLR7 agonist imiquimod is an effective adjunct treatment for a range of primary dermatological cancers. However, for therapy to be effective against a broad range of solid tumor types, it must promote a strong systemic antitumor response that targets metastases in addition to primary tumor. We therefore investigated the potential of locally delivered imiquimod to stimulate an effective systemic antitumor response in a murine model of malignant mesothelioma (AB1-HA) with primary and distal tumors (dual tumor). Persistent delivery of imiquimod into primary tumor significantly retarded tumor growth in all treated mice compared with vehicle control. This local antitumor immune response required both CD8 T cells and NK cells, but not CD4 T cells, and was reliant on type I IFN induction. In vivo CTL studies and Ly6A/E staining of lymphocytes suggested that local imiquimod treatment had indeed induced a systemic, Ag-specific CD8 response. However, notably this response was not sufficient to retard the growth of an untreated distal tumor. Because local imiquimod treatment did not induce significant CD4 T cell responses, we investigated the efficacy of combining imiquimod with agonistic CD40 Ab (as a surrogate for CD4 T cell help). Combination of locally delivered imiquimod with systemic anti-CD40 immunotherapy not only significantly enhanced the local antitumor response, with 30% complete resolution, but it was also effective at significantly retarding growth of distal tumor. These results demonstrate that antitumor responses induced by locally delivered TLR7 agonists can be harnessed systemically for treating distal tumor.
Inflammation Recapitulates the Ontogeny of Lymphoid Stromal Cells
Authors: Peduto Lucie , Dulauroy Sophie , Lochner Matthias , Späth Gerald F. , Morales Miguel A. , Cumano Ana , Eberl Gérard
Published: April 2009

Stromal cells in lymphoid tissues regulate lymphocyte recruitment and survival through the expression of specific chemokines and cytokines. During inflammation, the same signals recruit lymphocytes to the site of injury; however, the “lymphoid” stromal (LS) cells producing these signals remain poorly characterized. We find that mouse inflammatory lesions and tumors develop gp38+ LS cells, in recapitulation of the development of LS cells early during the ontogeny of lymphoid organs and the intestine, and express a set of genes that promotes the development of lymphocyte-permissive tissues. These gp38+ LS cells are induced by a robust pathway that requires myeloid cells but not known Toll- or NOD-like receptors, the inflammasome, or adaptive immunity. Parabiosis and inducible genetic cell fate mapping experiments indicate that local precursors, presumably resident fibroblasts rather that circulating precursors, massively proliferate and give rise to LS cells during inflammation. Our results show that LS cells are both programmed during ontogeny and reinduced during inflammation.
The Avidity and Lytic Efficiency of the CTL Response to HTLV-1
Authors: Kattan Tarek , MacNamara Aidan , Rowan Aileen G. , Nose Hirohisa , Mosley Angelina J. , Tanaka Yuetsu , Taylor Graham P. , Asquith Becca , Bangham Charles R. M.
Published: April 2009

In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV-1-specific CTLs can co-exist stably with a high proviral load and the proviral load is strongly correlated with the risk of HTLV-1-associated inflammatory diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are ineffective in controlling HTLV-1 replication but contribute to the pathogenesis of the inflammatory diseases. But evidence from host and viral immunogenetics and gene expression microarrays suggests that a strong CTL response is associated with a low proviral load and a low risk of HAM/TSP. Here, we quantified the frequency, lytic activity and functional avidity of HTLV-1-specific CD8+ cells in fresh, unstimulated PBMCs from individuals with natural HTLV-1 infection. The lytic efficiency of the CD8+ T cell response—the fraction of autologous HTLV-1-expressing cells eliminated per CD8+ cell per day—was inversely correlated with both the proviral load and the rate of spontaneous proviral expression. The functional avidity of HTLV-1-specific CD8+ cells was strongly correlated with their lytic efficiency. We conclude that efficient control of HTLV-1 in vivo depends on the CTL lytic efficiency, which depends in turn on CTL avidity of Ag recognition. CTL quality determines the position of virus-host equilibrium in persistent HTLV-1 infection.
α2-Macroglobulin Capture Allows Detection of Mast Cell Chymase in Serum and Creates a Reservoir of Angiotensin II-Generating Activity
Authors: Raymond Wilfred W. , Su Sharon , Makarova Anastasia , Wilson Todd M. , Carter Melody C. , Metcalfe Dean D. , Caughey George H.
Published: April 2009

Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by mast cells. When secreted from degranulating cells, it can interact with a variety of circulating antipeptidases, but is mostly captured by α2-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that α2-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used α2-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of ∼1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. α2-Macroglobulin-bound chymase generates angiotensin II in chymase-spiked serum, and it appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin-converting enzyme. These findings suggest that chymase bound to α2-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that α2-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases.
Cutting Edge: Shift in Antigen Dependence by an Antiviral MHC Class Ib-Restricted CD8 T Cell Response during Persistent Viral Infection
Authors: Swanson Phillip A. , Hofstetter Amelia R. , Wilson Jarad J. , Lukacher Aron E.
Published: April 2009

The requirement for Ag in maintaining memory CD8 T cells often differs between infections that are acutely resolved and those that persist. Using the mouse polyoma virus (PyV) persistent infection model, we recently described a novel CD8 T cell response directed to a PyV peptide presented by Q9, an MHC class Ib molecule. This antiviral Q9-restricted CD8 T cell response is characterized by a 3-mo expansion phase followed by a long-term plateau phase. In this study, we demonstrate that viral Ag is required for this protracted inflation phase but is dispensable for the maintenance of this Q9-restricted CD8 T cell response. Moreover, proliferation by memory T cells, not recruitment of naive PyV-specific T cells, is primarily responsible for Q9-restricted, anti-PyV CD8 T cell inflation. These data reveal a dynamic shift in Ag dependence by an MHC class Ib-restricted memory CD8 T cell response during a persistent viral infection.
Responsibility, God and society: The cry of the Other in the sacred texts as a challenge towards responsible global citizenship
Authors: Meylahn Johann-Albrecht
Published: April 2009

The article seeks to respond to the question: What role can the sacred texts play in the construction of a Christian identity that is responsible to the Other in a pluralistic global world? The sacred texts of the Judaic-Christian tradition offer not only an understanding of the wholly otherness of God, but also form the basis of our understanding and perception of humanity (anthropology), the world and ourselves (personhood/identity). This understanding is constructed in the context of responding to the call of the wholly Other and the others. Identities are traditionally constructed through the identification and exclusion of differences (otherness), thus leading to an ethic of exclusion and responsibility only to oneself/ourselves. Yet these identity-forming texts harbour a persistent otherness, which challenges these traditional identities by interrupting them with a call to responsibility toward the other. The otherness harboured in these texts takes various forms, namely: The otherness of the ancient world to our world, the otherness of the transcendental Other, and the otherness of the text itself, as there is always a différance that has not yet been heard. These various forms of otherness, of our identity-forming texts, deconstruct our identity constructions, thus calling us to a continuous responsibility towards the other. This call could form the basis of a Christian identity and ethic of global cosmopolitan citizenship that is always responding to the eschatological interruption by the other, who is not yet present or who has not been offered presence.
Chronic patient care at North West Province clinics
Authors: Van Deventer Claire , Couper Ian , Sondzaba Nontsikelelo
Published: April 2009

Background: Chronic illnesses are a significant burden to the health services in South Africa. There is a specific national health plan whereby chronically ill patients who are acceptably controlled should be managed at clinic level. The perception has emerged that the management of primary care has not been optimal in the Southern District of the North West Province. This provided the motivation to initiate this research, namely consideration of chronic patient care at clinics in the North West Province of South Africa.Method: A cross-sectional descriptive study was carried out at four randomly selected clinics covering four sub-districts in the Southern District (North West Province). This was done using charts and registers at the clinics. Inclusion criteria were patients older than 18, and presenting with the following chronic illnesses: asthma/chronic obstructive airways disease (COAD), hypertension, diabetes and epilepsy. The major focus areas were the regular assessment of the patients, the level of control of the illness and the use of the Essential Drugs List and Standard Treatment Guidelines (EDL/STG).Results: In the cases of all the chronic illnesses it was found that regular assessments were poorly done, with asthma (peak flow measurements) being the most poorly done. Control was generally less than 50% for all the illnesses, although the EDL was followed fairly well by the personnel at the clinics.Conclusion: In the light of the burden of chronic illness the results give cause for great concern about the quality of care for chronically ill patients, and reasons were sought for some of the poor results. A subsequent decision was taken to carry out comprehensive quality improvement projects on each of the illnesses over the following five years.
Ethylenebisthiocarbamates (Analysis)
Authors: Malik Ashok Kumar , Camara C.
Published: April 2009

Ethylenebisdithiocarbamates are widely used around the world to protect crops against different kinds of pests, and it is not surprising that these compounds can be detected at trace level in environmental samples. Stringent regulations have produced an increase in the number of methods developed for their determination. In this section, a brief introduction to the methods for the analysis of ethylenebisdithiocarbamate pesticides, followed by a more detailed discussion of individual methods, is presented. Analysis of ethylenebisdithiocarbamate residues and their decomposition products in foodstuffs, water, commercial samples, and various environmental samples using different techniques is the key feature of this article.
Fungicides, Antibiotics
Authors: Yamaguchi Isamu , Tagawa Michito
Published: April 2009

Antibiotics have an economic advantage over synthetic chemicals in that a variety of substances can be manufactured using one set of equipment and facilities. In addition, they are produced not from limited fossil resources, but from renewable agricultural products through fermentation by microorganisms. However, because of their highly specific mechanism of action, they are apt to suffer from the emergence of resistant strains. Thus, it is sometimes necessary to combine the agents with other chemicals that have different mechanisms of action or to use them in rotation. Nevertheless, molecular biology is making rapid advances, and more efficient production of microbial products will become possible by modern gene engineering.
Fungicides, Sterol Biosynthesis Inhibitors
Authors: Köllerm Wolfram
Published: April 2009

Because the potential of sterol biosynthesis inhibitors in the control of plant diseases was discovered in the late 1960s, this class has become one of the most widely use target‐specific, systemic fungicides. In contrast to other fungicide classes, their importance was not necessarily determined by a broad spectrum of disease control provided by each member of the class, but rather by an unprecedented number of commercial products with particular properties displayed by each member. For several diseases, the original efficacies of the class of sterol biosynthesis inhibitors has declined due to the development of resistance. The future role of this class of fungicides will continue to be substantial, in particular with the diversification of disease control measures aimed at delaying the development of resistance to other classes of fungicides.
Herbicides: Inhibitors of Glutamine Synthetase
Authors: Plimmer Jack , Gammon D. W.
Published: April 2009

Glufosinate‐ammonium is a nonselective contract herbicide. Glufosinate was introduced as a herbicide in 1981 and is used for controlling a wide range of annual and perennial broad‐leaved weeds in fruit orchards, vineyards, rubber and palm oil plantations, ornamental trees and brushes, noncropland, and pre‐emergence in vegetables. It is also used as a desiccant in potatoes, sunflowers, and so on. A number of crops have been genetically modified to tolerate glufosinate. These include field corn, canola, soybeans, and sugar beet.
Soil Microorganisms: Role in Biodegradation
Authors: Turco Ron
Published: April 2009

Over the last 100 years, the study of soil microbiology has revealed that a wide array of inherent biochemical abilities exist in each gram of soil. The study of microorganisms was hampered for many years by our inability to separate the cells from their growth environment. This makes the study of soil ecology unique because few other areas of ecological investigation have such difficulty in separating the studied organisms from their habitat. Therefore, the structure and function of soil reflects the interrelatedness of the organism and their habitat.
Microwave Phase Shifters
Authors: White Joseph F.
Published: April 2009

The sections in this article are

Scanning Array Antenna Applications

The Pin Diode

Loaded Line Phase Shifter

Lumped Element Phase Shifters

Constant Phase Shift With Frequency

Varactor Diode, Continuous Phase Shifter

The Fet as a Switching Device

Acknowledgment
Interval Analysis for Circuits
Authors: Kolev Lubomir V.
Published: April 2009

The sections in this article are

Interval Analysis

The Interval Approach

Areas of Application

Virtues and Drawbacks of the Interval Approach

Interval Arithmetic

Interval Functions

Interval Methods for Linear Equations

Interval Methods for Nonlinear Equations

Tolerances of Linear Circuits

Transient Tolerance Analysis

Global Analysis of Nonlinear DC Circuits

Alternative Applications

Robust Stability

Performance Characteristics

Improved Numerical Efficiency

Trends for Future Development
Multimedia Information Systems
Authors: Al‐Khatib Wasfi , Khan M. F. , Dağtaş Serhan , Ghafoor Arif
Published: April 2009

The sections in this article are

Requirements of Multimedia Information Systems

Notion of Time for Multimedia Data

Content‐Based Retrieval of Multimedia Data

Multimedia Document Modeling and Retrieval

Conclusion
Microstrip Lines
Authors: Ma Zhewang , Yamashita Eikichi , Atsuki Kazuhiko
Published: April 2009

The sections in this article are

Transverse Electromagnetic Transmission Lines

Striplines

Microstrip Lines

Other Topics
Microwave Detectors
Authors: Ham Ronald E.
Published: April 2009

The sections in this article are

Thermally Dependent Detectors

Diode Detectors
Microwave Isolators
Authors: Dunn Vernon E.
Published: April 2009

The sections in this article are

Terminated Circulators

Faraday Rotation Isolator

Resonance Isolators

Field Displacement Isolators
Microwave Oscillators
Authors: Mortazawi Amir
Published: April 2009

The sections in this article are

Modeling of Microwave Oscillators

Injection Locking of Microwave Oscillators

Noise in Oscillators

Gunn Oscillators

Impatt Oscillators

Dielectric Resonator Oscillators

Electronically Tunable Oscillators

Phase Lock Loops
Microwave Receivers
Authors: Bao‐yen Tsui James
Published: April 2009

The sections in this article are

Generic Receivers

Definitions Used in Receivers

Classification Of Receivers

Analog Intercept Receivers

Digital Receivers

Comparison of Different Types of Receivers
Microwave Switches
Authors: Caverly Robert H.
Published: April 2009

The sections in this article are

Microwave Switch: Terminology and Types

Microwave Switch Modeling

Microwave Switch Elements

Nonideal Microwave Switch Element Operation

Other Microwave Switch Elements

Additional Reading
International Communication
Authors: Driskill Linda P.
Published: April 2009

The sections in this article are

Language Issues in International Communication

Simplified Language Systems

Translation

Effects of National Laws on Communication

Effects of Cultural Differences

Interaction of National, Regional, Ethnic, and Corporate Factors

Influence of Corporate Norms and Policies

Corporate Policies About International Communication

Where to Find Help

The Demand for Increased International Communication

Influences of Culture on Communication Practices

Problems Related to International Communication

How to Communicate with International Audiences

Ethical Issues

Theories of International Communication

Research Methods

Issues for Future Study in International Communication
Intellectual Property in Engineering
Authors: Lechter Michael A.
Published: April 2009

The sections in this article are

The Different Types of Intellectual Property

Overview and Comparison of the Basic Mechanisms for Protecting Engineering Information

Need for Keeping Accurate Records

Conclusion
Injectable Biomaterials for Regenerating Complex Craniofacial Tissues
Authors: Kretlow James D. , Young Simon , Klouda Leda , Wong Mark , Mikos Antonios G.
Published: April 2009

Engineering complex tissues requires a precisely formulated combination of cells, spatiotemporally released bioactive factors, and a specialized scaffold support system. Injectable materials, particularly those delivered in aqueous solution, are considered ideal delivery vehicles for cells and bioactive factors and can also be delivered through minimally invasive methods and fill complex 3D shapes. In this review, we examine injectable materials that form scaffolds or networks capable of both replacing tissue function early after delivery and supporting tissue regeneration over a time period of weeks to months. The use of these materials for tissue engineering within the craniofacial complex is challenging but ideal as many highly specialized and functional tissues reside within a small volume in the craniofacial structures and the need for minimally invasive interventions is desirable due to aesthetic considerations. Current biomaterials and strategies used to treat craniofacial defects are examined, followed by a review of craniofacial tissue engineering, and finally an examination of current technologies used for injectable scaffold development and drug and cell delivery using these materials.
In Pursuit of Zero: Polymer Brushes that Resist the Adsorption of Proteins
Authors: Hucknall Angus , Rangarajan Srinath , Chilkoti Ashutosh
Published: April 2009

Protein resistant or “non‐fouling” surfaces are of great interest for a variety of biomedical and biotechnology applications. This article briefly reviews the development of protein resistant surfaces, followed by recent research on a new methodology to fabricate non‐fouling surfaces by surface‐initiated polymerization. We show that polymer brushes synthesized by surface‐initiated polymerization that present short oligo(ethylene glycol) side chains are exceptionally resistant to protein adsorption and cell adhesion. The importance of the protein and cell resistance conferred by these polymer brushes is illustrated by their use as substrates for the fabrication of antibody microarrays that exhibit femtomolar limits of detection in complex fluids such as serum and blood with relaxed requirements for intermediate wash steps. This example highlights the important point that the reduction in background noise afforded by protein‐resistant surfaces can greatly simplify the development of ultrasensitive heterogeneous, surface‐based clinical and proteomic assays with increased sensitivity and utility.
Richer milk for sons but more milk for daughters: Sex‐biased investment during lactation varies with maternal life history in rhesus macaques
Authors: Hinde Katherine
Published: April 2009

Lactation represents the greatest postnatal energetic expenditure for human and non‐human primate females, and the ability to sustain the costs of lactation is influenced by a mother's physical condition. This is especially true for young mothers that initiate reproduction shortly after adolescence. These mothers have fewer bodily reserves available for lactation and face tradeoffs between reproduction and their own growth. Milk synthesis among captive rhesus macaques (Macaca mulatta) was investigated at the California National Primate Research Center from 2005 to 2007 (N = 114). Rhesus macaques produced low energy density milk typical of the primate order, but there was substantial individual variation among mothers in both milk energy density and yield. As a consequence, the available milk energy (AME), the product of milk energy density and milk yield, to support infant growth, development, and activity, varied tenfold among mothers. Primiparous mothers (N = 40) had fewer bodily resources, as measured by mass and body mass index, available for lactation than did multiparous mothers (N = 74) and showed poorer lactational performance. Mothers of sons produced milk of higher energy density, especially primiparous mothers, but lower milk yield, such that AME was the same for sons and daughters. Although AME from the mother was the same for sons and daughters, there was significant sexual dimorphism in infant mass. These data indicate that selection has likely favored sex‐specific regulation of growth and development that is not necessarily contingent on greater maternal investment. Am. J. Hum. Biol. 2009. © 2009 Wiley‐Liss, Inc.
Inside Cover: hallium(I) as a Coordination Site Protection Agent: Preparation of an Isolable Zero‐Valent Nickel Tris‐Isocyanide (Angew. Chem. Int. Ed. 19/2009)
Authors: Fox Brian J. , Millard Matthew D. , DiPasquale Antonio G. , Rheingold Arnold L. , Figueroa Joshua S.
Published: April 2009

Binding of thallium(I) by low‐valent nickel establishes the use of main‐group ions as coordination site protection agents for transition‐metal centers. As described by J. S. Figueroa and co‐workers in their Communication on page 3473 ff., Tl(I) coordination provides a route to the preparation of a coordinatively unsaturated nickel tris‐isocyanide complex. Thallium functions as a protecting group towards Lewis bases and is readily removed upon addition of halide ions.

magnified image

Binding of thallium(I) by low‐valent nickel establishes the use of main‐group ions as coordination site protection agents for transition‐metal centers. As described by J. S. Figueroa and co‐workers in their Communication on page 3473 ff., Tl(I) coordination provides a route to the preparation of a coordinatively unsaturated nickel tris‐isocyanide complex. Thallium functions as a protecting group towards Lewis bases and is readily removed upon addition of halide ions.

magnified image
Insulin‐Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating Diabetes
Authors: Zhang Yu‐Hua , Wang He‐Feng , Liu Wei , Wei Bin , Bing Lu‐Jun , Gao Ying‐Mao
Published: April 2009

Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow‐derived mesenchymal stem cells (BMSCs) into insulin‐producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse‐transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox‐1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC‐implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test‐induced responses were observed in the IPC‐implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728–735, 2009. © 2009 Wiley‐Liss, Inc.
Comparative Anatomy and Evolution of the Cardiac Innervation in New World Monkeys (Platyrrhini, E. Geoffroy, 1812)
Authors: Kawashima Tomokazu , Thorington Richard W. , Whatton James F.
Published: April 2009

The morphology of the autonomic cardiac nervous system (ACNS) was examined in 24 sides of 12 New World monkeys (Platyrrhini) of all four families to document the morphology systematically and to study the evolutionary changes of the ACNS in this primate lineage. We report the following: (1) Although several trivial intra‐ and inter‐specific variations are present, a family‐dependent morphology of the ACNS does not exist in New World monkeys. (2) The sympathetic ganglia in New World monkeys consist of the superior cervical, the middle cervical, and the cervicothoracic which is composed of the inferior cervical and first and second thoracic, and the thoracic ganglia starting with the third thoracic. The general cardiac nervous system is the sympathetic middle and inferior cardiac nerves and all parasympathetic vagal cardiac branches. (3) The morphology of the ACNS in the New World monkeys is almost consistent regardless of the number of vertebrae, the cardiac position and deviation (axis), and the great arterial branching pattern of the aortic arch, and it is very similar to that in the Old World monkeys, with only one difference: the superior cervical ganglion in the New World monkeys tends to be relatively smaller, higher, and provides a narrower contribution to the spinal nerves than in the Old World monkeys. The ACNS morphology exhibits significant evolutionary changes within the primate lineage from New and Old World monkeys to humans. The comparative morphology within the lineage is concordant with the phylogeny, suggesting that the primate ACNS preserves its evolutionary history in close alignment with phylogeny. Anat Rec, 292:670–691, 2009. © 2009 Wiley‐Liss, Inc.
A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil
Authors: Kreiss Alexandre , Obendorf David L. , Hemsley Susan , Canfield Paul J. , Woods Gregory M.
Published: April 2009

Tasmanian devil (Sarcophilus harrisii) the world's largest carnivorous marsupial, at risk from extinction due to an infectious cancer, devil facial tumour disease. (This is one of the devils in our research population). See Kriess, et al., on page 611, in this issue.Anatomical Record 292:611–620.
Metal‐Promoted Nucleophilic Addition and Cyclization of Diamines with Dicyanonitrosomethanide, [C(CN)2(NO)]−
Authors: Chesman Anthony S. R. , Turner David R. , Deacon Glen B. , Batten Stuart R.
Published: April 2009

Additional cyclization: Dicyanonitrosomethanide, [C(CN)2(NO)]− undergoes nucleophilic addition and cyclization of 1,2‐diaminoethane and 1,3‐diaminopropane on the nitrile groups to form imidazolinyl and 1,4,5,6‐tetrahydropyrimidinyl groups, respectively. Ethanolamine has lower reactivity and fails to cyclize.

magnified image

The metal‐promoted nucleophilic addition of diaminoalkanes to dicyanonitrosomethanide, C(CN)2(NO)− (dcnm), and subsequent cyclization has been utilized in the synthesis of novel anionic species. The addition and cyclization of 1,2‐diaminoethane (en) to both nitrile groups of dcnm forms the anion diimidazolinylnitrosomethanide (dinm), isolated in the dinuclear complex [{Cu(dinm)(en)}2en][ClO4]2 (1). The same reaction solution yields [Cu(cinm)(ainm)] (cinm=cyanoimidazolinylnitrosomethanide, ainm=(((2‐aminoethyl)amino)iminomethyl)imidazolinylnitrosomethanide) (2), which contains intermediates of the dinm species, supporting a stepwise mechanism of addition of the diamine followed by cyclization. 1,3‐Diaminopropane (pn) added and cyclized on only one nitrile group to form a 1,4,5,6‐tetrahydropyrimidine ring. This resulted in the formation of the cyanonitroso‐1,4,5,6‐tetrahydropyrimidinylmethanide ligand (cnpm) in complexes with the general formula [M(cnpm)2(pn)] (M=Cu (3 a), Ni (3 b), Zn (3 c)). These reactions are contrasted to the addition of ethanolamine in the pyridine (py) complex [Ni(chnm)2(py)2]⋅(py) (4) (chnm=cyano((2‐hydroxyethyl)amino)iminomethylnitrosomethanide) with no cyclization, demonstrating the higher reactivity of amines compared with alcohols. The formation of the complexes [M(cmnm)2(mame)] (M=Co (5 a), Ni (5 b), cmnm=cyano(imino(methoxy)methyl)nitrosomethanide, mame=1‐dimethylamino‐2‐methylaminoethane) indicate mame may be too sterically hindered to add to dcnm under similar reaction conditions.
The immediate‐early oncoproteins Fra‐1, c‐Fos, and c‐Jun have distinguishable surface behavior and interactions with phospholipids
Authors: Gaggiotti María Cecilia , Del Boca Maximiliano , Castro Gonzalo , Caputto Beatriz L. , Borioli Graciela A.
Published: April 2009

This work explores the surface properties of the transcription factor Fra‐1 and compares them with those of two other immediate early proteins, c‐Fos and c‐Jun, to establish generalities and differences in the surface behavior and interaction with phospholipids of this type of proteins. We present several experimental clues of the flexible nature of Fra‐1, c‐Fos, and c‐Jun that support sequence‐based predictions of their intrinsical disorder. The values of surface parameters for Fra‐1 are similar in general to those of c‐Fos and c‐Jun. However, we find differences in the interactions of the three proteins with phospholipids. The closely related Fra‐1 and c‐Fos share affinity for anionic lipids but the former has more affinity for a condensed phase and senses a change in DPPC phase, while the latter has more affinity for an expanded phase. These features are in contrast with our previous finding that c‐Jun is not selective for phospholipid polar head group or charge. We show here that at least some immediate early transcription factors can interact with membrane phospholipids in a distinguishable manner, and this shall provide a basis for their potential capacity to regulate membrane‐mediated cellular processes. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 710–718, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Model‐based data evaluation of polyhydroxybutyrate producing mixed microbial cultures in aerobic sequencing batch and fed‐batch reactors
Authors: Johnson Katja , Kleerebezem Robbert , van Loosdrecht Mark C.M.
Published: April 2009

The production of polyhydroxyalkanoates (PHAs) with mixed microbial cultures is a promising approach for the sustainable production of bioplastics. Usually a two‐step process is employed consisting of (i) the enrichment of a PHA producing mixed culture in a sequencing batch reactor (SBR) and (ii) the subsequent PHA production in a fed‐batch reactor. Both reactors are highly dynamic systems, particularly if the SBR is working at low sludge residence times (SRTs) or if growth is (partly) permitted in fed‐batch systems. Under these conditions the concentrations of substrate, PHA and biomass change rapidly, complicating the identification of biomass specific conversion rates as required for process characterization. We developed a structured approach for the evaluation of such SBR and fed‐batch experiments consisting of five steps: (1) Measurement of a sufficiently large set of parameters including off‐gas concentrations, (2) Corrections of measurements for effects of sampling and addition of liquids (pH control, substrate), (3) Calculation of oxygen uptake and carbon dioxide evolution rates, the latter including inorganic carbon dissolved in the liquid phase, (4) Balancing of the measured conversions, (5) Evaluation of the measurements by means of a metabolic model. This approach has been successfully applied to a large number of data sets. Steps 1–4 ensured that data sets of high quality were obtained. Step 5 allowed to find the best estimates for all conversions and biomass specific rates for the measured data sets, while complying with material balances. Conversions of the substrate acetate, the nitrogen source ammonia and of the storage polymer PHA (here polyhydroxybutyrate (PHB)) were described very accurately by the model. Modeled off‐gas conversions often deviated somewhat from measured conversions, which might be partly due to an inaccurate model stoichiometry. Nonetheless, the described approach proved to be a very useful tool for the evaluation and comparison of PHB producing cultures. Biotechnol. Bioeng. 2009; 104: 50–67 © 2009 Wiley Periodicals, Inc.
Measurement of anal cushions in idiopathic faecal incontinence
Authors: Thekkinkattil D K , Dunham R J , O'Herlihy S , Finan P J , Sagar P M , Burke D A
Published: April 2009

Background

Faecal incontinence affects a heterogeneous population and aetiology can be multifactorial. In a subset of patients the aetiology remains idiopathic despite standard investigations. Anal cushions are important in normal continence, but have rarely been studied. The aim of this study was to measure the size of the anal cushions and to evaluate their role in patients with idiopathic faecal incontinence.

Methods

Women in whom idiopathic faecal incontinence was diagnosed after standard anorectal investigations underwent transvaginal ultrasonography. The area of the anal cushions was measured and a cushion : canal (C : C) ratio derived, which was compared with that in a control group of women without faecal incontinence.

Results

Some 21 patients with incontinence (median age 60 years) and 102 asymptomatic controls (median age 41 years) underwent scanning. The median (interquartile range) C : C ratio in the symptomatic group was significantly lower than that for controls (0·57 (0·54–0·66) versus 0·68 (0·61–0·73) respectively; P = 0·001). C : C ratio was not influenced by age (r = 0·023, P = 0·821).

Conclusion

The C : C ratio was reduced in patients with idiopathic faecal incontinence.
Web‐based laboratory for engineering education
Authors: Stefanovic Miladin , Matijevic Milan , Cvijetkovic Vladimir , Simic Visnja
Published: April 2009

Laboratory experiments and practical work by their nature are unavoidable, important, and costly in the engineering education environment. The web laboratory is an educational tool for teaching students the basic principles and methodology in performing a series of experiments on different equipment at any time and from any location through the Internet. In this paper, pre‐requests, architecture, and software realization of the Web Laboratory at University of Kragujevac are presented. Organization, development, goals, and possible demands of the laboratory exercise: The inverted pendulum/gantry crane controls (with the capability to test different control algorithms) are also discussed. The applications of the web lab have been tested with the students enrolled at University of Kragujevac and the initial educational results of the implementation of this laboratory exercise are presented. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 526–536, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20222