bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-17–Dependent, IFN-γ–Independent Tumor Rejection Is Mediated by Cytotoxic T Lymphocytes and Occurs at Extraocular Sites, but Is Excluded from the Eye
Authors: Coursey Terry G. , Chen Peter W. , Niederkorn Jerry Y. 
Published: September 2011

Abstract
Although intraocular tumors reside in an immune-privileged site where immune responses are suppressed, some tumors are rejected. An example of this is the rejection of intraocular adenovirus-induced (adenovirus type 5 early region 1 [Ad5E1]) tumors in C57BL/6 mice. We previously identified an Ad5E1 tumor clone in which the rejection is IFN-γ dependent and culminates in the destruction of both the tumor and the eye. Although Ad5E1 tumors are not rejected when transplanted into the eyes of IFN-γ KO mice, they are rejected after s.c. transplantation. Thus, outside of the eye Ad5E1 tumors elicit a form of tumor immunity that is IFN-γ independent. In this article, we demonstrate that IFN-γ–independent s.c. rejection requires both CD4+ and CD8+ T cells. Furthermore, s.c. tumor rejection requires IL-17, which is produced by IFN-γ–deficient CD4+ T cells in response to tumor Ags (TAs). Splenocytes from CD4-depleted IFN-γ KO mice produce significantly less IL-17 compared with splenocytes from isotype-treated IFN-γ KO animals in response to TAs. Furthermore, depletion of IL-17 decreases CTL activity against Ad5E1 tumor cells. In this model we propose that, in the absence of IFN-γ, CD4+ T cells produce IL-17 in response to TAs, which increases CTL activity that mediates tumor rejection; however, this does not occur in the eye. IL-6 production within the eye is severely reduced, which is consistent with the failure to induce Th17 cells within the intraocular tumors. In contrast, the s.c. environment is replete with IL-6 and supports the induction of Th17 cells. Therefore, IFN-γ–independent tumor rejection is excluded from the eye and may represent a newly recognized form of ocular immune privilege.
Myeloid Differentiation Factor-2 Interacts with Lyn Kinase and Is Tyrosine Phosphorylated Following Lipopolysaccharide-Induced Activation of the TLR4 Signaling Pathway
Authors: Gray Pearl , Dagvadorj Jargalsaikhan , Michelsen Kathrin S. , Brikos Constantinos , Rentsendorj Altan , Town Terrence , Crother Timothy R. , Arditi Moshe 
Published: September 2011

Abstract
Stimulation with LPS induces tyrosine phosphorylation of numerous proteins involved in the TLR signaling pathway. In this study, we demonstrated that myeloid differentiation factor-2 (MD-2) is also tyrosine phosphorylated following LPS stimulation. LPS-induced tyrosine phosphorylation of MD-2 is specific; it is blocked by the tyrosine kinase inhibitor, herbimycin A, as well as by an inhibitor of endocytosis, cytochalasin D, suggesting that MD-2 phosphorylation occurs during trafficking of MD-2 and not on the cell surface. Furthermore, we identified two possible phospho-accepting tyrosine residues at positions 22 and 131. Mutant proteins in which these tyrosines were changed to phenylalanine had reduced phosphorylation and significantly diminished ability to activate NF-κB in response to LPS. In addition, MD-2 coprecipitated and colocalized with Lyn kinase, most likely in the endoplasmic reticulum. A Lyn-binding peptide inhibitor abolished MD-2 tyrosine phosphorylation, suggesting that Lyn is a likely candidate to be the kinase required for MD-2 tyrosine phosphorylation. Our study demonstrated that tyrosine phosphorylation of MD-2 is important for signaling following exposure to LPS and underscores the importance of this event in mediating an efficient and prompt immune response.
Retinal Self-Antigen Induces a Predominantly Th1 Effector Response in Axl and Mertk Double-Knockout Mice
Authors: Ye Fei , Han Lixia , Lu Qingjun , Dong Wanwei , Chen Zhenwen , Shao Hui , Kaplan Henry J. , Li Qiutang , Lu Qingxian 
Published: September 2011

Abstract
The TAM family of receptors (Tyro3, Axl, and Mertk) plays an important role in the negative regulation of response of dendritic cells (DCs) and macrophages to pathogenic stimuli, and mice lacking this receptor family develop spontaneous lupus-like systemic autoimmunity against a variety of tissues, including retina. To study the molecular mechanism underlying the TAM regulation of APC functions and subsequent effects on the induction of an autoimmune response against the eye, we examined CD4 T cell differentiation following retinal self-antigen immunization. CD4 T cells prepared from naive or interphotoreceptor retinoid-binding protein (IRBP)1-20–immunized Axl and Mertk double-knockout (dko) mice reacted to activation using anti-CD3 and anti-CD28 Abs or to bolster by self-antigen in vitro with a predominantly Th1 effector response, as characterized by increased IFN-γ production and higher frequency of IFN-γ–positive CD4 T cells. The Th17 effector response to IRBP immunization was similar in dko mice to that in wild-type controls, as shown by ELISA measurement of IL-17A in the culture medium and flow cytometric analysis of IL-17A–secreting CD4 T cells. Interestingly, APCs or DCs isolated from IRBP-immunized dko mice exhibited a greater ability to drive the Th1 response. The production of two driving cytokines for Th1 differentiation, IL-12 and IL-18, was dramatically increased in dko DCs and macrophages, and LPS stimulation bolstered their production. The preferential development into the Th1 subset in dko mice suggests that the cytokine milieu produced by the mutant mice in vivo or by mutant APCs in vitro selectively creates a differentiation environment favoring the Th1 effector response.
Characterization of a Transitional Preplasmablast Population in the Process of Human B Cell to Plasma Cell Differentiation
Authors: Jourdan Michel , Caraux Anouk , Caron Gersende , Robert Nicolas , Fiol Geneviève , Rème Thierry , Bolloré Karine , Vendrell Jean-Pierre , Le Gallou Simon , Mourcin Frédéric , De Vos John , Kassambara Alboukadel , Duperray Christophe , Hose Dirk , Fest Thierry , Tarte Karin , Klein Bernard 
Published: September 2011

Abstract
The early steps of differentiation of human B cells into plasma cells are poorly known. We report a transitional population of CD20low/−CD38− preplasmablasts along differentiation of human memory B cells into plasma cells in vitro. Preplasmablasts lack documented B cell or plasma cell (CD20, CD38, and CD138) markers, express CD30 and IL-6R, and secrete Igs at a weaker level than do plasmablasts or plasma cells. These preplasmablasts further differentiate into CD20−CD38highCD138− plasmablasts and then CD20−CD38highCD138+ plasma cells. Preplasmablasts were fully characterized in terms of whole genome transcriptome profiling and phenotype. Preplasmablasts coexpress B and plasma cell transcription factors, but at a reduced level compared with B cells, plasmablasts, or plasma cells. They express the unspliced form of XBP1 mRNA mainly, whereas plasmablasts and plasma cells express essentially the spliced form. An in vivo counterpart (CD19+CD20low/−CD38−IL-6R+ cells) of in vitro-generated preplasmablasts could be detected in human lymph nodes (0.06% of CD19+ cells) and tonsils (0.05% of CD19+ cells). An open access “B to Plasma Cell Atlas,” which makes it possible to interrogate gene expression in the process of B cell to plasma cell differentiation, is provided. Taken together, our findings show the existence of a transitional preplasmablast population using an in vitro model of plasma cell generation and of its in vivo counterpart in various lymphoid tissues.
Regulatory T Cells in Patients with Whipple’s Disease
Authors: Schinnerling Katina , Moos Verena , Geelhaar Anika , Allers Kristina , Loddenkemper Christoph , Friebel Julian , Conrad Kristina , Kühl Anja A. , Erben Ulrike , Schneider Thomas 
Published: September 2011

Abstract
Classical Whipple’s disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflammatory reaction and the absence of T. whipplei-specific Th1 reactivity support persistence and systemic spread of the pathogen. In this article, we hypothesized that regulatory T cells (Treg) are involved in immunomodulation in CWD, and we asked for the distribution, activation, and regulatory capacity of Treg in CWD patients. Whereas in the lamina propria of CWD patients before treatment numbers of Treg were increased, percentages in the peripheral blood were similar in CWD patients and healthy controls. However, peripheral Treg of CWD patients were more activated than those of controls. Elevated secretion of IL-10 and TGF-β in the duodenal mucosa of CWD patients indicated locally enhanced Treg activity. Enhanced CD95 expression on peripheral memory CD4+ T cells combined with reduced expression of IFN-γ and IL-17A upon polyclonal stimulation by CD4+ cells from untreated CWD patients further hinted to Treg activity-related exhaustion of effector CD4+ T cells. In conclusion, increased numbers of Treg can be detected within the duodenal mucosa in untreated CWD, where huge numbers of T. whipplei-infected macrophages are present. Thus, Treg might contribute to the chronic infection and systemic spread of T. whipplei in CWD but in contrast prevent mucosal barrier defect by reducing local inflammation.
Liposomal Encapsulation of Glucocorticoids Alters Their Mode of Action in the Treatment of Experimental Autoimmune Encephalomyelitis
Authors: Schweingruber Nils , Haine Axel , Tiede Karsten , Karabinskaya Anna , van den Brandt Jens , Wüst Simone , Metselaar Josbert M. , Gold Ralf , Tuckermann Jan P. , Reichardt Holger M. , Lühder Fred 
Published: September 2011

Abstract
Glucocorticoids (GCs) are widely used to treat acute relapses of multiple sclerosis (MS). In this study, we demonstrate that liposomal encapsulation augments the therapeutic potency of GCs as they ameliorate experimental autoimmune encephalomyelitis (EAE) to the same extent as free GC, but at strongly reduced dosage and application frequency. Importantly, this is accompanied by an altered mode of action. Unlike free GCs, which mainly target T lymphocytes during EAE therapy, liposomal GCs only marginally affect T cell apoptosis and function. In contrast, liposomal GCs efficiently repress proinflammatory macrophage functions and upregulate anti-inflammatory genes associated with the alternatively activated M2 phenotype. The GC receptor (GR) per se is indispensable for the therapeutic efficacy of liposomal GC. In contrast to free GCs, however, the individual deletion of the GR either in T cells or myeloid cells has little effect on the efficacy of liposomal GCs in the treatment of EAE. Only the combined deletion of the GR in both cellular compartments markedly compromises the therapeutic effect of liposomal GCs on disease progression. In conclusion, encapsulation of GC does not only enhance their efficacy in the treatment of EAE but also alters their target cell specificity and their mode of action compared with free GCs.
Insights into HLA-Restricted T Cell Responses in a Novel Mouse Model of Dengue Virus Infection Point toward New Implications for Vaccine Design
Authors: Weiskopf Daniela , Yauch Lauren E. , Angelo Michael A. , John Daisy V. , Greenbaum Jason A. , Sidney John , Kolla Ravi V. , De Silva Aruna D. , de Silva Aravinda M. , Grey Howard , Peters Bjoern , Shresta Sujan , Sette Alessandro 
Published: September 2011

Abstract
The frequency of dengue virus (DENV) infection has increased dramatically in the last few decades, and the lack of a vaccine has led to significant morbidity and mortality worldwide. To date, a convenient murine system to study human T cell responses to DENV has not been available. Mice transgenic for HLA are widely used to model human immune responses, and it has been shown that mouse-passaged DENV is able to replicate to significant levels in IFN-α/βR−/− mice. To cover a wide range of HLA phenotypes, we backcrossed IFN-α/βR−/− mice with HLA A*0201, A*0101, A*1101, B*0702, and DRB1*0101-transgenic mice. A DENV proteome-wide screen identified a total of 42 epitopes across all HLA-transgenic IFN-α/βR−/− strains tested. In contrast, only eight of these elicited responses in the corresponding IFN-α/βR+/+ mice. We were able to identify T cell epitopes from 9 out of the 10 DENV proteins. However, the majority of responses were derived from the highly conserved nonstructural proteins NS3 and NS5. The relevance of this model is further demonstrated by the fact that most of the epitopes identified in our murine system are also recognized by PBMC from DENV-exposed human donors, and a dominance of HLA B*0702-restricted responses has been detected in both systems. Our results provide new insights into HLA-restricted T cell responses against DENV, and we describe in this study a novel murine model that allows the investigation of T cell-mediated immune mechanisms relevant to vaccine design.
Liquid Chromatography‐Mass Spectrometry in Analytical Clinical Chemistry
Authors: Sluss, PhD Patrick M. 
Published: September 2011

Abstract
This article is intended to provide a basic understanding of the principles and current configurations of liquid chromatography tandem mass spectrometry (LC/MS/MS) technologies used in clinical laboratories. Multidimensional liquid chromatography (LC), interfacing with mass spectrometry (MS) using soft ionization systems, and the principles of modern mass spectrometers, quadrupole, time‐of‐flight (TOF), and Fourier transform ion cyclotron resonance, are discussed. The principles of ion traps and orbitraps are discussed as these technologies are increasingly being applied in clinical laboratories. As LC/MS/MS applications in the clinical laboratory continue to grow at an unprecedented rate, it is critical for clinical pathologists and laboratorians to understand the principles, design, and limitations of the technologies involved.
Microwave‐Assisted Sample Preparation for Spectrochemistry
Authors: Nóbrega Joaquim A. , Donati George L. 
Published: September 2011

AbstractMicrowave‐assisted sample preparation was a major developmental step in combining the overall quality and speediness of spectrochemical analysis with the initial step of converting solid samples into representative solutions. Instrumentation and applications for organic and inorganic samples are discussed in detail after briefly addressing the fundamentals of the method. The feasibility of using diluted acid solutions and pressurized oxygen vessels for sample digestion is rationalized and clearly related to recent advances in reaction vessel materials and the interaction between matter and microwave radiation. Applications based on microwave‐induced combustion (MIC) and procedures developed for chemical speciation are also highlighted. A list of ideal attributes for microwave‐assisted sample preparation is proposed and evaluated considering the state of the art. Major needs, mainly related to the capacity of digesting large sample masses and improvements in sample throughput, are also pointed out.
Structure and Dynamics of Carbohydrate Residues. Fluorescence Spectroscopy Studies
Authors: Albani Jihad R. 
Published: September 2011

AbstractStructure of carbohydrate residues are in general studied via NMR. In the present study, we are describing structural and dynamical studies of carbohydrates bound to α1‐acid glycoprotein using fluorescence spectroscopy as a tool. Also, we applied fluorescence spectroscopy to show importance of a specific fucose in the interaction and stability of two proteins.
Earprint Comparison: Admissibility of Evidence in Court
Authors: Moenssens Andre 
Published: September 2011

Abstract
The admissibility of the conclusion an examiner reached comparing anatomical features observed in a crime scene latent earprint of unknown provenance with corresponding features that may exist in the known image of a suspect's ears has long been a contentious issue in courts that operate in an adversarial system of justice based on Common Law. This article explores the two major appellate‐level decisions on that issue, both of which concluded that the earprint comparison evidence offered in the cases should not have been admitted as evidence. Some further analysis of legal principles that may come into play in such cases is also presented.
Eyewitness Memory Issues in Civil Litigation
Authors: Weaver Charles A. , Krug Kevin S. , Trent Terrell J. , Holmes Amanda E. , Parra Karenna F. 
Published: September 2011

AbstractThe reconstructive nature of memory affects all long‐term recollection—all of us have misremembered events from our past, confused events from different time frames, or failed to remember the names of colleagues. Memory errors in the courtroom are significantly more serious. Mistaken identification can send an innocent person to prison, and those in the legal community acknowledge the valuable contribution of memory researchers in minimizing these errors. But memory plays an equally large role in many areas of civil litigation. Focusing particularly on product liability cases, this article addresses memory in civil litigation. Memory experts do not have any special ability to distinguish true from false memories, in the absence of corroboration. Their expertise, however, encompasses a scientific understanding of factors that are likely to affect the reliability of memories beyond common knowledge and of material assistance to the trier of fact.
Relativistic Electronic Structure Theory for Molecular Spectroscopy
Authors: Mastalerz Remigius , Reiher Markus 
Published: September 2011

AbstractThis review provides a concise introduction to relativistic electronic structure theory with a focus on the prediction of parameters relevant for molecular spectroscopy. For this purpose, a brief overview of wave‐function‐based electronic structure methods with a special focus on the calculation of electron correlation effects is given. These are essential for an accurate prediction of spectroscopic parameters from first‐principles calculations. Then approximate relativistic Hamiltonians are discussed in detail regarding their accuracy and range of application. Thea posterioricalculation of spin–orbit effects from correlated wave functions is briefly described and reviewed. The presentation concludes with an extensive discussion of calculated results for prototypical molecules. The focus is mainly on small molecules to which highly accurate relativistic methods can be applied and close agreement with experimental data can be achieved.
Global Analytical Potential Energy Surfaces for High‐resolution Molecular Spectroscopy and Reaction Dynamics
Authors: Marquardt Roberto , Quack Martin 
Published: September 2011

AbstractAnalytical representations of potential energy hypersurfaces for the nuclear motion in polyatomic molecules from ab initio theory and experiment are discussed in a general way. The qualification of potential hypersurface representations from ab initio theory regarding the description of experimental data from rovibrational high‐resolution spectroscopy and chemical reaction kinetics is analyzed in more detail for a restricted group of molecules including methane, CH4, ammonia, NH3, H2O2, and (HF)2. Current methods for the derivation of analytical representations of potential energy surfaces as well as some applications are reviewed.
Indeterminacies of Fitting Parameters in Molecular Spectroscopy
Authors: Watson James K.G. 
Published: September 2011

AbstractAnalyses of molecular spectra often use the idea of aneffective Hamiltonian, in which the dynamical variables are the degrees of freedom involved in the spectrum, and the effects of the other degrees of freedom are represented by the values of various parameters. However, it may not be possible to determine all these parameters by empirical fits of the spectra because different parameters may make indistinguishable contributions to the eigenvalues of the Hamiltonian. This article reviews a number of examples of such indeterminacies, including applications to vibration–rotation spectra of diatomic molecules, without or with corrections for the breakdown of the Born–Oppenheimer approximations; electron‐spin structure in diatomic molecules; centrifugal distortion in asymmetric‐top molecules; vibration–rotation resonances in polyatomic molecules; vibration–rotation interactions in degenerate vibrational states; and internal rotation. The discussion of these indeterminacies involves unitary transformations that are expanded as infinite series. This procedure may break down if the convergence of the series is slow. The study of near‐singularities of least‐squares matrices associated with the presence of indeterminacies is also discussed.
Using Iterative Methods to Compute Vibrational Spectra
Authors: Carrington Tucker 
Published: September 2011

AbstractIn this article, some modern methods for computing vibrational energies of polyatomic molecules are reviewed. The emphasis is on iterative methods with which a spectrum is obtained by evaluating matrix–vector products. To use such methods one does not need to compute or store Hamiltonian matrix elements. If each basis function is a product of functions of a single coordinate, matrix–vector products can be computed by doing sequentailly sums associated with indices of the individual coordinates. The corresponding algorithm is simple and useful, but, with current computers, it cannot be applied to compute the spectrum of a six‐atom molecule. For molecules with six or more atoms (and often for molecules with five atoms), it is necessary to use basis set contraction. A contraction method is presented that has been used for methane and CH5+.
Fourier Transform Microwave Spectroscopy of Doped Helium Clusters
Authors: Jäger Wolfgang , Xu Yunjie 
Published: September 2011

Abstract

In this article, we describe investigations of rotational spectra of complexes and clusters containing helium atoms. These systems are of much interest mainly because of their very low binding energies and the associated relatively large zero‐point energies. As a result, these very weakly bonded systems undergo large amplitude internal stretching and bending motions and the semirigid rotor Hamiltonian can often not describe the spectra appropriately. Microwave spectra of clusters of the type He

N

‐linear molecule are discussed. The number of helium atoms in the cluster,
N
, ranges from 1 up to 39 in the case of He

N

‐carbonyl sulfide. It was possible to record transitions of clusters of successively increasing size and to extract spectroscopic parameters of clusters with atom‐by‐atom resolution. Probably the most significant outcome from these studies is the observation of an increase in the rotational constant,
B
, with increasing
N
. This turnaround occurs at relatively small numbers of helium atoms, e.g.,
N
= 9 for He

N

‐OCS. The corresponding decrease in moment of inertia with increasing
N
is attributed to a decoupling of helium density from the rotational motion of the dopant molecule. This is interpreted in terms of the occurrence of superfluid effects on the microscopic scale. Throughout the article, we emphasize the importance of our colleagues in infrared spectroscopy and theory collaborating in this research endeavor.