bluuebunny/crossref_metadata_2025_split huggingface dataset:
GVHD after haploidentical transplantation: a novel, MHC-defined rhesus macaque model identifies CD28− CD8+ T cells as a reservoir of breakthrough T-cell proliferation during costimulation blockade and sirolimus-based immunosuppression
Authors: Miller Weston P. , Srinivasan Swetha , Panoskaltsis-Mortari Angela , Singh Karnail , Sen Sharon , Hamby Kelly , Deane Taylor , Stempora Linda , Beus Jonathan , Turner Alexa , Wheeler Caleb , Anderson Daniel C. , Sharma Prachi , Garcia Anapatricia , Strobert Elizabeth , Elder Eric , Crocker Ian , Crenshaw Timothy , Penedo M. Cecilia T. , Ward Thea , Song Mingqing , Horan John , Larsen Christian P. , Blazar Bruce R. , Kean Leslie S. 
Published: September 2010

AbstractWe have developed a major histocompatibility complex–defined primate model of graft-versus-host disease (GVHD) and have determined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this disease. Severe GVHD developed after haploidentical transplantation without prophylaxis, characterized by rapid clinical decline and widespread T-cell infiltration and organ damage. Mechanistic analysis showed activation and possible counter-regulation, with rapid T-cell expansion and accumulation of CD8+ and CD4+ granzyme B+ effector cells and FoxP3pos/CD27high/CD25pos/CD127low CD4+ T cells. CD8+ cells down-regulated CD127 and BCl-2 and up-regulated Ki-67, consistent with a highly activated, proliferative profile. A cytokine storm also occurred, with GVHD-specific secretion of interleukin-1 receptor antagonist (IL-1Ra), IL-18, and CCL4. Costimulation Blockade and Sirolimus (CoBS) resulted in striking protection against GVHD. At the 30-day primary endpoint, CoBS-treated recipients showed 100% survival compared with no survival in untreated recipients. CoBS treatment resulted in survival, increasing from 11.6 to 62 days (P < .01) with blunting of T-cell expansion and activation. Some CoBS-treated animals did eventually develop GVHD, with both clinical and histopathologic evidence of smoldering disease. The reservoir of CoBS-resistant breakthrough immune activation included secretion of interferon-γ, IL-2, monocyte chemotactic protein-1, and IL-12/IL-23 and proliferation of cytotoxic T-lymphocyte–associated antigen 4 immunoglobulin-resistant CD28− CD8+ T cells, suggesting adjuvant treatments targeting this subpopulation will be needed for full disease control.
Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma
Authors: Reis Patricia P , Tomenson Miranda , Cervigne Nilva K , Machado Jerry , Jurisica Igor , Pintilie Melania , Sukhai Mahadeo A , Perez-Ordonez Bayardo , Grénman Reidar , Gilbert Ralph W , Gullane Patrick J , Irish Jonathan C , Kamel-Reid Suzanne 
Published: September 2010

AbstractBackgroundThe tumor suppressor Programmed Cell Death 4 (PDCD4) has been found to be under-expressed in several cancers and associated with disease progression and metastasis. There are no current studies characterizing PDCD4 expression and its clinical relevance in Oral Squamous Cell Carcinoma (OSCC). Since nodal metastasis is a major prognostic factor in OSCC, we focused on determining whether PDCD4 under-expression was associated with patient nodal status and had functional relevance in OSCC invasion. We also examinedPDCD4regulation by microRNA 21 (miR-21) in OSCC.ResultsPDCD4mRNA expression levels were assessed in 50 OSCCs and 25 normal oral tissues.PDCD4was under-expressed in 43/50 (86%) OSCCs, with significantly reduced mRNA levels in patients with nodal metastasis (p = 0.0027), and marginally associated with T3-T4 tumor stage (p = 0.054). PDCD4 protein expression was assessed, by immunohistochemistry (IHC), in 28/50 OSCCs and adjacent normal tissues; PDCD4 protein was absent/under-expressed in 25/28 (89%) OSCCs, and marginally associated with nodal metastasis (p = 0.059). A matrigel invasion assay showed that PDCD4 expression suppressed invasion, and siRNA-mediated PDCD4 loss was associated with increased invasive potential of oral carcinoma cells. Furthermore, we showed that miR-21 levels were increased in PDCD4-negative tumors, and thatPDCD4expression may be down-regulated in OSCC by direct binding of miR-21 to the 3'UTRPDCD4mRNA.ConclusionsOur data show an association between the loss of PDCD4 expression, tumorigenesis and invasion in OSCC, and also identify a mechanism of PDCD4 down-regulation by microRNA-21 in oral carcinoma. PDCD4 association with nodal metastasis and invasion suggests that PDCD4 may be a clinically relevant biomarker with prognostic value in OSCC.
An ethnobotanical survey of plants used to manage HIV/AIDS opportunistic infections in Katima Mulilo, Caprivi region, Namibia
Authors: Chinsembu Kazhila C , Hedimbi Marius 
Published: September 2010

AbstractKatima Mulilo has the highest burden of HIV/AIDS in Namibia. Due to several constraints of the antiretroviral therapy programme, HIV-infected persons still use ethnomedicines to manage AIDS-related opportunistic infections. Despite the reliance on plants to manage HIV/AIDS in Katima Mulilo, there have been no empirical studies to document the specific plant species used by traditional healers to treat AIDS-related opportunistic infections. In this study, an ethnobotanical survey was conducted to record the various plant families, species, and plant parts used to manage different HIV/AIDS-related opportunistic infections in Katima Mulilo, Caprivi region, Namibia. The results showed that a total of 71 plant species from 28 families, mostly the Combretaceae (14%), Anacardiaceae (8%), Mimosaceae (8%), and Ebanaceae (7%), were used to treat conditions such as herpes zoster, diarrhoea, coughing, malaria, meningitis, and tuberculosis. The most plant parts used were leaves (33%), bark (32%), and roots (28%) while the least used plant parts were fruits/seeds (4%). Further research is needed to isolate the plants' active chemical compounds and understand their modes of action.
In Situ Electrodeposited FePt Nanoparticles for Oxygen Reduction with High Activity and Long-term Stability
Authors: Liu Di , Tian Yang , Zhu Anwei , Luo Yongping 
Published: September 2010

Abstract
In this letter, a low-cost, procedurally simple, and environmentally friendly strategy has been developed for in situ electrodeposition of FePt nanoparticles on l-cysteine-modified gold electrode surfaces. The as-prepared 20 nm FePt nanoparticles show high activity toward ORR, which is comparable with that of commercial Pt catalyst. In addition, the electrodeposited FePt nanoparticles exhibit relatively long-term stability, possibly because the alloyed Fe may prevent the dissolution of small Pt nanoparticles in the ORR.
Soziale Interaktion über Real-Time Collaboration-Systeme – Empirische Befunde und Entwurfsmuster
Authors: Joisten Martina , Gross Tom 
Published: September 2010

Zusammenfassung
Real-Time Collaboration-Systeme unterstützen die einfache Kommunikation und die Zusammenarbeit zwischen zwei oder mehreren Benutzern, die gleichzeitig im System online sind. Obgleich sich diese Systeme in den letzten Jahren in der Praxis enorm verbreitet haben, fehlen größtenteils systematische Befunde zu deren Gestaltung, die auf langfristigen Nutzerstudien basieren. In diesem Artikel präsentieren wir Gestaltungserkenntnisse und -empfehlungen für Real-Time Collaboration-Systeme, die sowohl auf soziologischen Theorien zur Technologienutzung und zu sozialer Interaktion als auch auf einer empirischen Untersuchung fußen.
The Virtual Patient for Education and Training: A Critical Review of the Literature
Authors: Haag Martin , Huwendiek Sören 
Published: September 2010

Abstract
Nowadays, virtual patients are becoming increasingly essential for high-quality medical education since there are not enough actual patients available for educational and training purposes. However, development and curricular integration of virtual patients is challenging and time consuming. This review gives an overview on relevant aspects of development and usage of virtual patients and shows the current state of development. The included information is sourced from relevant literature of the last 15 years and the longstanding experience of the authors in the relevant fields.
Acute Pancreatitis in Association With Type 2 Diabetes and Antidiabetic Drugs
Authors: Gonzalez-Perez Antonio , Schlienger Raymond G. , Rodríguez Luis A. García 
Published: September 2010

OBJECTIVE
Previous observational studies have found an increased risk of acute pancreatitis among type 2 diabetic patients. However, limited information is available on this association and specifically on the role of antidiabetic treatment. Our aim, therefore, was to further assess the risk of acute pancreatitis in adult patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
We performed a population-based case-control analysis nested in a cohort of 85,525 type 2 diabetic patients and 200,000 diabetes-free individuals from the general population using data from The Health Improvement Network database. Subjects were followed up to ascertain incident cases of acute pancreatitis.

RESULTS
We identified 419 cases of acute pancreatitis, 243 in the general population and 176 in the diabetes cohort. Incidence rates were 30.1 and 54.0 per 100,000 person-years in the general population and the diabetes cohort, respectively. In the cohort analysis, the adjusted incidence rate ratio of acute pancreatitis in diabetic patients versus that in the general population was 1.77 (95% CI 1.46–2.15). The magnitude of this association decreased with adjustment for multiple factors in the nested case-control analysis (adjusted odds ratio 1.37 [95% CI 0.99–1.89]). Furthermore, we found that the risk of acute pancreatitis was decreased among insulin-treated diabetic patients (0.35 [0.20–0.61]).

CONCLUSIONS
Type 2 diabetes may be associated with a slight increase in the risk of acute pancreatitis. We also found that insulin use in type 2 diabetes might decrease this risk. Further research is warranted to confirm these associations.
A1C and Diabetes Diagnosis Among Filipino Americans, Japanese Americans, and Native Hawaiians
Authors: Araneta Maria Rosario G. , Grandinetti Andrew , Chang Healani K. 
Published: September 2010

OBJECTIVE
To examine the sensitivity and specificity of A1C ≥6.5% to diagnose diabetes among Filipino Americans, Japanese Americans, and Native Hawaiians.

RESEARCH DESIGN AND METHODS
This was a cross-sectional study among middle-aged adults without prior diagnosis of type 2 diabetes who completed a 2-h 75-g oral glucose tolerance test (OGTT) and A1C measures.

RESULTS
The 933 participants had a mean age of 54.2 years, and 73% were women. A total of 425 (45.5%) subjects had impaired fasting glucose or impaired glucose tolerance, 145 (15.5%) had type 2 diabetes (by OGTT), and 83 (8.9%) had A1C ≥6.5%. The sensitivity and specificity of A1C ≥6.5% to define diabetes (by OGTT) was 40.0 and 96.8% and 68.9 and 95.3%, respectively (by fasting plasma glucose only). However, (64.8%) of Filipino and Japanese subjects with diabetes had isolated postchallenge hyperglycemia; AIC ≥6.5% sensitivity and specificity was 19.1 and 92.1%, respectively, to define isolated postchallenge hyperglycemia in the total sample.

CONCLUSIONS
A1C ≥6.5% had low sensitivity and may delay diagnosis of type 2 diabetes without OGTT. This limitation is exacerbated by isolated postchallenge hyperglycemia in Asian Americans.
Induction of programmed cell death in Arabidopsis and rice by single‐wall carbon nanotubes
Authors: Shen Cong‐Xiang , Zhang Quan‐Fang , Li Jian , Bi Fang‐Cheng , Yao Nan 
Published: September 2010

• Premise of the study: Single‐walled carbon nanotubes (SWCNTs) have many unique structural and mechanical properties. Their potential applications, especially in biomedical engineering and medical chemistry, have been increasing in recent years, but the toxicological impact of nanoparticles has rarely been studied in plants.• Methods: We exposed Arabidopsis and rice leaf protoplasts to SWCNTs and examined cell viability, DNA damage, reactive oxygen species generation, and related gene expression. We also tested the effects of nanoparticles on Arabidopsis leaves after injecting a SWCNT solution. EM‐TUNEL (electron‐microscopic terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling) and a cerium chloride staining method were used.• Key results: SWCNTs caused adverse cellular responses including cell aggregation, chromatin condensation along with a TUNEL‐positive reaction, plasma membrane deposition, and H2O2 accumulation. The effect of SWCNTs on the survival of cells was dose dependent, with 25 μg/mL inducing 25% cell death in 6 h. In contrast, activated carbon, which is not a nano‐sized carbon particle, did not induce cell death even 24 h after treatments. The data indicated that the nano‐size of the particle is a critical factor for toxicity. Moreover, endocytosis‐like structures with cerium chloride deposits formed after SWCNT treatment, suggesting a possible pathway for nanoparticles to traverse the cell membrane.• Conclusions: Consequently, SWCNTs have an adverse effect on protoplasts and leaves through oxidative stress, leading to a certain amount of programmed cell death. Although nanomaterials have great advantages in many respects, the benefits and side effects still need to be assessed carefully.
Isolation and characterization of microsatellite markers in an endangered species Dracaena cambodiana (Liliaceae)
Authors: Zhang Lu , Li Qiao‐Ming 
Published: September 2010

•Premise of the study: The development of microsatellite primers in the endangered species Dracaena cambodiana will be the foundation for genetic and conservation studies of D. cambodiana and several Dracaena species.•Methods and Results: A total of 26 microsatellite markers were developed in Chinese populations of D. cambodiana, using the Fast Isolation by AFLP of Sequences Containing Repeats (FIASCO) protocol. Among them, sixteen primer pairs generated polymorphic loci (fourteen of them successfully amplified in other four Dracaena species) and ten primer pairs produced monomorphic loci.•Conclusions: These microsatellite markers could be used in the further investigation of population genetics of D. cambodiana and other Dracaena species.
Microsatellite markers for the cushion rock jasmine, Androsace tapete (Primulaceae), a species endemic to the Qinghai‐Tibetan Plateau
Authors: Zeng Liyan , Li Zhonghu , Tashi Tsering , Chen Jian , Zhong Yang , Geng Yupeng 
Published: September 2010

• Premise of the study: Microsatellite markers were developed in an alpine plant endemic to the Qinghai‐Tibetan Plateau, Androsace tapete, to investigate its spatial genetic structure, gene flow, and mating patterns.• Methods and Results: Using the combined biotin capture method, 16 microsatellite primer sets were isolated and characterized. Fifteen of these markers showed polymorphism, and the number of alleles per locus ranged from three to 13 across 56 individuals from six Tibetan populations.• Conclusions: These markers provide a useful tool to investigate the spatial genetic structure, gene flow, and mating system of A. tapete.
Inhibition of NF-κB Signaling in Human Dendritic Cells by the Enteropathogenic Escherichia coli Effector Protein NleE
Authors: Vossenkämper Anna , Marchès Olivier , Fairclough Peter D. , Warnes Gary , Stagg Andrew J. , Lindsay James O. , Evans Paul C. , Luong Le A. , Croft Nicholas M. , Naik Sandhia , Frankel Gad , MacDonald Thomas T. 
Published: September 2010

Abstract
Intestinal dendritic cells (DCs) send processes between epithelial cells into the gut lumen to sample pathogens. Noninvasive enteropathogenic Escherichia coli (EPEC) colonize the gut using a type three secretion system (T3SS) to inject effector proteins into epithelial cells. We hypothesized that EPEC might also inject proteins into DC processes to dampen immune recognition. Using a T3SS-linked fluorescence resonance energy transfer-based system we show that EPEC injects effectors into in vitro grown human myeloid DCs. Injected cells emit a blue signal due to cleavage of the green fluorescence resonance energy transfer-based substrate CCF2/AM by β-lactamase. When cultured with a mutant EPEC unable to translocate effector proteins, myeloid DCs show rapid activation of NF-κB, secrete large amounts of proinflammatory cytokines and increase expression of CD80, CD83, and CD86, whereas wild-type EPEC barely elicits cytokine production and shuts off nuclear translocation of NF-κB p65. By deleting effector protein genes, we identified NleE as being critical for this effect. Expression of NleE in HeLa cells completely prevented nuclear p65 accumulation in response to IL1-β, and luciferase production in an NF-κB reporter cell line. DCs cocultured with wild-type EPEC or NleE-complemented strains were less potent at inducing MLR. EPEC was also able to inject effectors into DCs sending processes through model gut epithelium in a transwell system and into Peyer’s patch myeloid DCs. Thus, EPEC translocate effectors into human DCs to dampen the inflammatory response elicited by its own pathogen-associated molecular patterns.
Chemoattractant Receptors and Lymphocyte Egress from Extralymphoid Tissue: Changing Requirements during the Course of Inflammation
Authors: Brown Meghan N. , Fintushel Sarah R. , Lee Michael H. , Jennrich Silke , Geherin Skye A. , Hay John B. , Butcher Eugene C. , Debes Gudrun F. 
Published: September 2010

Abstract
Memory/effector T cells traffic efficiently through extralymphoid tissues, entering from the blood and leaving via the afferent lymph. During inflammation, T cell traffic into the affected tissue dramatically increases; however, the dynamics and mechanisms of T cell exit from inflamed tissues are poorly characterized. In this study, we show, using both a mouse and a sheep model, that large numbers of lymphocytes leave the chronically inflamed skin. Many T cells capable of producing IFN-γ and IL-17 also entered the draining afferent lymph, demonstrating that memory/effector T cells egress from sites of inflammation. Whereas efficient egress from acutely inflamed skin required lymphocyte-expressed CCR7, chronic inflammation promoted significant CCR7-independent exit as well. Lymphocyte exit at late time points of inflammation was sensitive to pertussis toxin but was only partially affected by the drug FTY720, implying the contribution of alternative chemoattractant receptors other than spingosine 1-phosphate receptor 1. Our data show that CCR7 is an important receptor for lymphocyte egress from both resting and inflamed extralymphoid tissues, but that alternative exit receptors come into play during chronic inflammation.
Responses against a Subdominant CD8+ T Cell Epitope Protect against Immunopathology Caused by a Dominant Epitope
Authors: Ruckwardt Tracy J. , Luongo Cindy , Malloy Allison M. W. , Liu Jie , Chen Man , Collins Peter L. , Graham Barney S. 
Published: September 2010

Abstract
CD8+ T cell responses are critical for the control of virus infections. Following infection, epitope-specific responses establish an unpredictable but reproducible pattern of dominance that is dictated by a large number of both positive and negative factors. Immunodomination, or diminution of subdominant epitope-specific responses by dominant epitopes, can play a substantial role in the establishment of epitope hierarchy. To determine the role of a dominant (KdM282–90) and a subdominant (DbM187–195) epitope of respiratory syncytial virus in viral control and immunodomination, MHC-binding anchor residues in the two epitopes were mutated individually in recombinant infectious viruses, greatly reducing or deleting the epitope-specific CD8+ T cell responses. Neither mutation negatively affected viral clearance in mice, and compensation by the unmutated epitope was seen in both cases, whereas compensation by five other subdominant epitopes was minimal. Mutation of the dominant KdM282–90 response resulted in effective viral clearance by the subdominant epitope with less illness, whereas mutation of the subdominant DbM187–195 response resulted in overcompensation of the already dominant KdM282–90 epitope, and increased severity of illness. Increased illness was associated with poor functionality of the abundant population of CD8+ T cells specific to the dominant KdM282–90 epitope, as measured by the percentage and magnitude of IFN-γ production. These data demonstrate efficient viral clearance, and a protective effect of subdominant CD8+ T cell responses.
Novel Zirconia–Alumina Nanocomposites Combining High Strength and Toughness
Authors: Gadow Rainer , Kern Frank 
Published: September 2010

AbstractAlumina toughened zirconia (ATZ) composites, combining a matrix of tetragonal zirconia polycrystals (TZP) and an alumina dispersion, are known for their high strength, toughness, and abrasion resistance. Depending on the type of stabilizing oxide in TZP the materials can be tailored to be either extremely strong (Y–TZP) or extremely tough (Ce–TZP) with a considerable cutback in the complementary property. Novel nanocomposite ATZ materials consisting of TZP co‐stabilized by neodymium and yttrium oxide (Nd–Y–TZP) combined with a reinforcement of 0–40 vol% alumina were produced to achieve high bending strength of 1200–1500 MPa at a toughness of 8–12 MPa·√m. TZP was produced by coating monoclinic nanopowder with 1.5 mol% yttria and 1.5 mol% neodymia. The powder was then blended with submicron size alumina and consolidated by hot pressing. Mechanical and microstructural properties were investigated.
Combinatorial and High‐Throughput Screening of Biomaterials
Authors: Simon Carl G. , Lin‐Gibson Sheng 
Published: September 2010

AbstractCombinatorial and high‐throughput methods have been increasingly used to accelerate research and development of new biomaterials. These methods involve creating miniaturized libraries that contain many specimens in one sample in the form of gradients or arrays, followed by automated data collection and analysis. This article reviews recent advances in utilizing combinatorial and high‐throughput methods to better understand cell–material interactions, particularly highlighting our efforts at the NIST Polymers Division. Specifically, fabrication techniques to generate controlled surfaces (2D) and 3D cell environments (tissue engineering scaffolds) as well as methods to characterize and analyze material properties and cell–material interactions are described. In conclusion, additional opportunities for combinatorial methods for biomaterials research are noted, including streamlined sample fabrication and characterization, appropriate and automated bioassays, and data analysis.