bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galiximab Signals B-NHL Cells and Inhibits the Activities of NF-κB–Induced YY1- and Snail-Resistant Factors: Mechanism of Sensitization to Apoptosis by Chemoimmunotherapeutic Drugs
Authors: Martinez-Paniagua Melisa A. , Vega Mario I. , Huerta-Yepez Sara , Baritaki Stavroula , Vega Gabriel G. , Hariharan Kandasamy , Bonavida Benjamin 
Published: January 2012

AbstractGaliximab (anti-CD80 monoclonal antibody) is a primatized (human IgG1 constant regions and cynomologus macaque variable regions) monoclonal antibody that is currently in clinical trials. Galiximab inhibits tumor cell proliferation through possibly cell signaling–mediated effects. Thus, we hypothesized that galiximab may signal the tumor cells and modify intracellular survival/antiapoptotic pathways such as the NF-κB pathway. This hypothesis was tested using various CD80+ Burkitt B-NHL (non–Hodgkin lymphomas) cell lines as models. Treatment of B-NHL cells with galiximab (25–100 μg/mL) resulted in significant inhibition of NF-κB activity and its target resistant factors such as YY1, Snail, and Bcl-2/Bcl-XL. Treatment of B-NHL cells with galiximab sensitized the tumor cells to both cis-diamminedichloroplatinum(II) (CDDP)- and TRAIL-induced apoptosis. The important roles of YY1- and Snail-induced inhibition by galiximab in the sensitization to CCDP and TRAIL were corroborated following transfection of Raji cells with YY1 or Snail short interfering RNA. The transfected cells were shown to become sensitive to both CCDP- and TRAIL-induced apoptosis in the absence of galiximab. Furthermore, knockdown of YY1 or Snail inhibited Bcl-XL. The involvement of Bcl-XL inhibition in sensitization was corroborated by the use of the pan-Bcl-2 inhibitor 2MAM-3 whereby the treated cells were sensitive to both CDDP- and TRAIL-induced apoptosis. These findings show that galiximab inhibits the NF-κB/Snail/YY1/Bcl-XL circuit that regulates drug resistance in B-NHL and in combination with cytotoxic drugs results in apoptosis. The findings also support the therapeutic application of the combination of galiximab and cytotoxic drugs in the treatment of drug-resistant CD80-positive B-cell malignancies. Mol Cancer Ther; 11(3); 572–81. ©2012 AACR.
Diagnosing Snowband Predictability Using a Multimodel Ensemble System
Authors: Novak David R. , Colle Brian A. 
Published: January 2012

Abstract
The forecast uncertainty of mesoscale snowband formation and evolution is compared using predictions from a 16-member multimodel ensemble at 12-km grid spacing for the 25 December 2002, 12 February 2006, and 14 February 2007 northeast U.S. snowstorms. Using these predictions, the case-to-case variability in the predictability of band formation and evolution is demonstrated. Feature-based uncertainty information is also presented as an example of what may be operationally feasible from postprocessing information from future short-range ensemble forecast systems. Additionally, the initial condition sensitivity of band location in each case is explored by contrasting the forecast evolutions of initial condition members with large differences in snowband positions. Considerable uncertainty in the occurrence, and especially timing and location, of band formation and subsequent evolution was found, even at forecast projections &lt;24 h. The ensemble provided quantitative mesoscale band uncertainty information, and differentiated between high-predictability (14 February 2007) and low-predictability (12 February 2006) cases. Among the three cases, large (small) initial differences in the upper-level PV distribution and surface mean sea level pressure of the incipient cyclone were associated with large (small) differences in forecast snowband locations, suggesting that case-to-case differences in predictability may be related to the quality of the initial conditions. The complexity of the initial flow may also be a discriminator. Error growth was evident in each case, consistent with previous mesoscale predictability research, but predictability differences were not correlated to the degree of convection. Discussion of these results and future extensions of the work are presented.
The Use of Real‐Time Image Stabilization and Augmented Reality Eyewear in the Treatment of Oscillopsia
Authors: Pothier David D. , Hughes Cian , Dillon Wanda , Ranalli Paul J. , Rutka John A. 
Published: January 2012

Objectives/HypothesisThe symptom of oscillopsia in patients with bilateral vestibular loss (BVL) can be reduced as dynamic visual acuity (DVA), the reduction in visual acuity during head movement, is improved by using real‐time image stabilization, delivered by augmented reality eyewear.SettingTertiary multidisciplinary neurotology clinic.Study DesignProspective experimental study.MethodsImmersive virtual reality glasses used in combination with a compact digital video camera were used. A software algorithm was developed that used a center‐weighted Lucas‐Kanade optical flow method to stabilize video in real time. Six patients with BVL were tested for changes in DVA using the eyewear. The ability to read a Snellen chart during a 2‐Hz oscillating head rotation DVA test was measured.ResultsFor combined scores of vertical and horizontal head rotations, the mean number of lines readable at rest was 7.86, which dropped to 2.77 with head movement (a combination of vertical and horizontal perturbations). This increased to a mean of 6.14 lines with the image stabilization software being activated. This difference was statistically significant (P<. 001).ConclusionThis is the first successful attempt to improve dynamic visual acuity in patients with bilateral vestibular loss. Recent hardware upgrades are promising in improving these results even further.
Individual finger synchronized robot-assisted hand rehabilitation in subacute to chronic stroke: a prospective randomized clinical trial of efficacy
Authors: Hwang Chang Ho , Seong Jin Wan , Son Dae-Sik 
Published: January 2012

Objective: To evaluate individual finger synchronized robot-assisted hand rehabilitation in stroke patients. Design: Prospective parallel group randomized controlled clinical trial. Subjects: The study recruited patients who were ≥18 years old, more than three months post stroke, showed limited index finger movement and had weakened and impaired hand function. Patients with severe sensory loss, spasticity, apraxia, aphasia, disabling hand disease, impaired consciousness or depression were excluded. Interventions: Patients received either four weeks (20 sessions) of active robot-assisted intervention (the FTI (full-term intervention) group, 9 patients) or two weeks (10 sessions) of early passive therapy followed by two weeks (10 sessions) of active robot-assisted intervention (the HTI (half-term intervention) group, 8 patients). Patients underwent arm function assessments prior to therapy (baseline), and at 2, 4 and 8 weeks after starting therapy. Results: Compared to baseline, both the FTI and HTI groups showed improved results for the Jebsen Taylor test, the wrist and hand subportion of the Fugl-Meyer arm motor scale, active movement of the 2nd metacarpophalangeal joint, grasping, and pinching power ( P < 0.05 for all) at each time point (2, 4 and 8 weeks), with a greater degree of improvement for the FTI compared to the HTI group ( P < 0.05); for example, in Jebsen Taylor test (65.9 ± 36.5 vs. 46.4 ± 37.4) and wrist and hand subportion of the Fugl-Meyer arm motor scale (4.3 ± 1.9 vs. 3.4 ± 2.5) after eight weeks. Conclusions: A four-week rehabilitation using a novel robot that provides individual finger synchronization resulted in a dose-dependent improvement in hand function in subacute to chronic stroke patients.
Osteoblast viability on hydroxyapatite with well-adjusted submicron and micron surface roughness as monitored by the proliferation reagent WST-1
Authors: Holthaus Marzellus Große , Treccani Laura , Rezwan Kurosch 
Published: January 2012

The impact of the cell surface roughness on titanium alloys used for biomedical implants has been extensively studied, whereas the dependency of human osteoblast viability on hydroxyapatite (HA) submicron and micron surface roughness has hitherto not yet been investigated in detail. Therefore, we investigate in this study the effect of HA substrates with different well-adjusted surface roughness on human osteoblast proliferation using the standard colorimetric reagent WST-1. By grinding, we obtained HA surfaces with six levels of well-defined surface roughness ranging from Sa = 3.36 µm down to 0.13 µm, resulting in hydrophilic contact angles from 11° to 27°. Energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray fluorescence measurements confirmed that neither grinding paper residues nor changes of the crystal structure were introduced to the HA substrates by the grinding process. By applying this simple surface treatment, we were able to isolate other effects from surface chemistry, crystal structure, and relative density. The changes of the osteoblast proliferation (WST-1 assay) on these different roughened HA surfaces after 7 days were found to be insignificant ( p > 0.05), evaluated by one-way analysis of variance and Tuckey’s Multiple Comparison Method. The results of this study show that all roughened HA surfaces, regardless of the microtopography, are biocompatible and allow osteoblast attachment, proliferation, and collagen type I production. The comparison with surface roughness used for standard Ti-based implants yielded that for HA no finishing process is necessary to ensure a sound human osteoblast cell proliferation in vitro.
Houttuyniae Herba protects rat primary cortical cells from Aβ25–35-induced neurotoxicity via regulation of calcium influx and mitochondria-mediated apoptosis
Authors: Park H , Oh MS 
Published: January 2012

Amyloid beta (Aβ) fibrils are believed to play a major role in the pathogenesis of Alzheimer’s disease. Although the mechanisms underlying Aβ toxicity remain largely unknown, Aβ fibrils disrupt calcium homeostasis and generate free radicals, resulting in oxidative stress, mitochondrial dysfunction, and apoptotic cell death. Houttuyniae Herba, the aerial part of Houttuynia cordata Thunb. (Saururaceae), is a commonly used herb in traditional Asian medicine. It has been reported to have various bioactivities, including antioxidant effects. In the present study, we investigated the protective effect of standardised Houttuyniae Herba water extract (HCW) against Aβ25–35-induced neurotoxicity and its possible mechanisms in rat primary cortical cells. Pretreatment with HCW attenuated the cell damage caused by 8 μM Aβ25–35 exposure, as evidenced by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a lactate dehydrogenase assay, and microtubule-associated protein 2 immunostaining. Moreover, HCW inhibited the Aβ25–35-induced elevation of the intracellular calcium level, reactive oxygen species overproduction, mitochondrial membrane potential disruption, and caspase 3 activation. These results indicate that HCW protects rat primary cortical neurons against Aβ25–35-induced toxicity via the regulation of calcium and the inhibition of mitochondria-mediated apoptosis.
Targeting of GSK3β promotes imatinib-mediated apoptosis in quiescent CD34+ chronic myeloid leukemia progenitors, preserving normal stem cells
Authors: Reddiconto Giovanni , Toto Claudia , Palamà Ilaria , De Leo Simone , de Luca Emanuela , De Matteis Serena , Dini Luciana , Passerini Carlo Gambacorti , Di Renzo Nicola , Maffia Michele , Coluccia Addolorata Maria Luce 
Published: January 2012

Abstract
The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)–initiating cells. Activation of β-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL–dependent Y phosphorylation and impaired binding to GSK3β (glycogen synthase kinase 3β). Herein, we show that GSK3β is constitutively Y216 phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3β activity and its altered subcellular localization were correlated with BCR-ABL–dependent and –independent activation of MAPK and p60-SRC/GSK3β complex formation. Specifically, GSK3β activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL– and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl–negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the β-catenin, cyclinD1, C-EBPα, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib.
Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma
Authors: Santo Loredana , Hideshima Teru , Kung Andrew L. , Tseng Jen-Chieh , Tamang David , Yang Min , Jarpe Matthew , van Duzer John H. , Mazitschek Ralph , Ogier Walter C. , Cirstea Diana , Rodig Scott , Eda Homare , Scullen Tyler , Canavese Miriam , Bradner James , Anderson Kenneth C. , Jones Simon S. , Raje Noopur 
Published: January 2012

Abstract
Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.
Benchmarks for flexible and rigid transcription factor-DNA docking
Authors: Kim RyangGuk , Corona Rosario I , Hong Bo , Guo Jun-tao 
Published: January 2012

Abstract

Background
Structural insight from transcription factor-DNA (TF-DNA) complexes is of paramount importance to our understanding of the affinity and specificity of TF-DNA interaction, and to the development of structure-based prediction of TF binding sites. Yet the majority of the TF-DNA complexes remain unsolved despite the considerable experimental efforts being made. Computational docking represents a promising alternative to bridge the gap. To facilitate the study of TF-DNA docking, carefully designed benchmarks are needed for performance evaluation and identification of the strengths and weaknesses of docking algorithms.

Results
We constructed two benchmarks for flexible and rigid TF-DNA docking respectively using a unified non-redundant set of 38 test cases. The test cases encompass diverse fold families and are classified into easy and hard groups with respect to the degrees of difficulty in TF-DNA docking. The major parameters used to classify expected docking difficulty in flexible docking are the conformational differences between bound and unbound TFs and the interaction strength between TFs and DNA. For rigid docking in which the starting structure is a bound TF conformation, only interaction strength is considered.

Conclusions
We believe these benchmarks are important for the development of better interaction potentials and TF-DNA docking algorithms, which bears important implications to structure-based prediction of transcription factor binding sites and drug design.
Geographic Information System and tools of spatial analysis in a pneumococcal vaccine trial
Authors: Tanskanen Antti , Nillos Leilani T , Lehtinen Antti , Nohynek Hanna , Sanvictores Diozele Hazel M , Simões Eric AF , Tallo Veronica L , Lucero Marilla G ,   ARIVAC Consortium
Published: January 2012

Abstract

Background
The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns.

Method
A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area.

Results
We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way.

Conclusions
The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural.

Trial registration number
ISRCTN: ISRCTN62323832
Interleukin-34 produced by human fibroblast-like synovial cells in rheumatoid arthritis supports osteoclastogenesis
Authors: Hwang Seung-Jun , Choi Bongkun , Kang Soon-Suk , Chang Jae-Ho , Kim Yong-Gil , Chung Yeon-Ho , Sohn Dong Hyun , So Min Wook , Lee Chang-Keun , Robinson William H , Chang Eun-Ju 
Published: January 2012

Abstract
Introduction
Interleukin-34 (IL-34) is a recently defined cytokine, showing a functional overlap with macrophage colony stimulating factor (M-CSF). This study was undertaken to address the expression of IL-34 in rheumatoid arthritis (RA) patients and to investigate its regulation and pathogenic role in RA.

Methods
IL-34 levels were determined in the RA synovium, synovial fluid (SF) and fibroblast-like synovial cells (FLS) by immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay and immunoblotting. RA activity was assessed using Disease Activity Score 28 (DAS28) activity in the plasma collected at baseline and one year after treatment. Conditioned media (CM) were prepared from RA FLS culture with tumor necrosis factor alpha (TNFα) for 24 hours and used for functional assay.

Results
IL-34 was expressed in the synovium, SF, and FLS from RA patients. The production of IL-34 in FLS was up-regulated by TNFα in RA samples compared with osteoarthritis (OA) patients. Importantly, the preferential induction of IL-34 rather than M-CSF by TNFα in RAFLS was mediated by the transcription factor nuclear factor kappa B (NF-κB) and activation of c-Jun N-terminal kinase (JNK). IL-34 elevation in plasma from RA patients was decreased after the administration of disease-modifying anti-rheumatic drugs (DMARDs) in accordance with a decrease in DAS28. CM from RAFLS cultured with TNFα promoted chemotactic migration of human peripheral blood mononuclear cells (PBMCs) and subsequent osteoclast (OC) formation, effects that were attenuated by an anti-IL-34 antibody.

Conclusions
These data provide novel information about the production of IL-34 in RA FLS and indicate that IL-34 is an additional osteoclastogenic factor regulated by TNFα in RA, suggesting a discrete role of IL-34 in inflammatory RA diseases.
A novel p38-MAPK signaling axis modulates neutrophil biology in head and neck cancer
Authors: Dumitru Claudia A , Fechner Maren K , Hoffmann Thomas K , Lang Stephan , Brandau Sven 
Published: January 2012

ABSTRACTNeutrophils are emerging as important mediators in cancer progression. Recent studies associated neutrophils with poor clinical outcome of HNC patients and showed that HNC induces recruitment, survival, and release of proinflammatory factors by neutrophils in vitro. The molecular mechanisms through which HNC and other cancers modulate neutrophil biology are currently unknown. To explore these mechanisms, we used an in vitro system that models the interaction between human HNC cells and neutrophils or neutrophilic-differentiated HL-60 cells, respectively. We show that HNC-derived factors activate p38-MAPK in neutrophils, which partly promotes neutrophil survival, but not neutrophil recruitment and motility. Most importantly, HNC-induced p38-MAPK activation strongly stimulates the release of CCL4, CXCL8, and MMP9 by neutrophils. We identify CREB and interestingly, p27 phosphorylated at T198 as downstream members of the HNC-induced p38-MAPK signaling cascade. Using siRNA technology, we demonstrate that p27 and CREB mediate the release of CCL4 and CXCL8 and that CREB, additionally, mediates the release of MMP9. These data unravel novel molecular mechanisms involved in regulation of neutrophil proinflammatory functions. Our studies on human HNC tissues indicate that tumor-infiltrating neutrophils might be a major source of CCL4 and particularly, MMP9 in cancer patients. Thus, our findings provide novel, mechanistic insights relevant for the pathophysiology of HNC and possibly, other types of cancer as well.
Doing Nothing: Adults With Disabilities With No Daily Activities and Their Siblings
Authors: Taylor Julie Lounds , Hodapp Robert M 
Published: January 2012

Abstract
A significant concern of parents and professionals is that adults with intellectual and developmental disabilities will go without regular educational–vocational activities. The authors examined predictors of such inactivity in individuals with intellectual and developmental disabilities, as well as how inactivity related to their sibling's well-being and the sibling relationship. Participants included 796 siblings of adults with intellectual and developmental disabilities who responded to a web-based survey. Nearly 13% of adults with intellectual and developmental disabilities were without daytime activities; these adults had more emotional–behavioral and health problems, were more underserved by the formal service system, and had parents who were less able to provide care. Although siblings of adults without activities reported more depressive symptoms, worse health, and less close sibling relationships, inactivity no longer predicted these problems after controlling for characteristics that predisposed adults with intellectual and developmental disabilities to have no activities.