bluuebunny/crossref_metadata_2025 huggingface dataset:
The transcription factor RBP-J-mediated signaling is essential for dendritic cells to evoke efficient anti-tumor immune responses in mice
Authors: Feng Fan , Wang Yao-Chun , Hu Xing-Bin , Liu Xiao-Wei , Ji Gang , Chen Yun-Ru , Wang Lin , He Fei , Dou Guo-Rui , Liang Liang , Zhang Hong-Wei , Han Hua
Published: April 2010

Background

Dendritic cells (DCs) are professional antigen presenting cells that initiate specific immune responses against tumor cells. Transcription factor RBP-J-mediated Notch signaling regulates DC genesis, but whether this pathway regulates DC function in anti-tumor immunity remains unclear. In the present work we attempted to identify the role of Notch signaling in DC-mediated anti-tumor immune response.

Results

When DCs were co-inoculated together with tumor cells, while the control DCs repressed tumor growth, the RBP-J deficient DCs had lost tumor repression activity. This was most likely due to that DCs with the conditionally ablated RBP-J were unable to evoke anti-tumor immune responses in the solid tumors. Indeed, tumors containing the RBP-J deficient DCs had fewer infiltrating T-cells, B-cells and NK-cells. Similarly, the draining lymph nodes of the tumors with RBP-J-/- DCs were smaller in size, and contained fewer cells of the T, B and NK lineages, as compared with the controls. At the molecular level, the RBP-J deficient DCs expressed lower MHC II, CD80, CD86, and CCR7, resulting in inefficient DC migration and T-cell activation in vitro and in vivo. T-cells stimulated by the RBP-J deficient DCs did not possess efficient cytotoxicity against tumor cells, in contrast to the control DCs.

Conclusion

The RBP-J-mediated Notch signaling is essential for DC-dependent anti-tumor immune responses. The deficiency of RBP-J impairs the DC-based anti-tumor immunity through affecting series of processes including maturation, migration, antigen presentation and T-cell activation. The Notch signaling pathway might be a target for the establishment of the DC-based anti-tumor immunotherapies.
Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission
Authors: Li Lin , Qiao Pengyuan , Yang Jie , Lu Lu , Tan Suiyi , Lu Hong , Zhang Xiujuan , Chen Xi , Wu Shuguang , Jiang Shibo , Liu Shuwen
Published: April 2010

Background

Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission.

Results

Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low in vitro cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells.

Conclusion

ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.
Inflammation and Nerve Injury Induce Expression of Pancreatitis-Associated Protein-II in Primary Sensory Neurons
Authors: He Shao-Qiu , Yao Jun-Ru , Zhang Fang-Xiong , Wang Qiong , Bao Lan , Zhang Xu
Published: April 2010

Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.
The BARRIERS scale -- the barriers to research utilization scale: A systematic review
Authors: Kajermo Kerstin Nilsson , Boström Anne-Marie , Thompson David S , Hutchinson Alison M , Estabrooks Carole A , Wallin Lars
Published: April 2010

Background

A commonly recommended strategy for increasing research use in clinical practice is to identify barriers to change and then tailor interventions to overcome the identified barriers. In nursing, the BARRIERS scale has been used extensively to identify barriers to research utilization.

Aim and objectives

The aim of this systematic review was to examine the state of knowledge resulting from use of the BARRIERS scale and to make recommendations about future use of the scale. The following objectives were addressed: To examine how the scale has been modified, to examine its psychometric properties, to determine the main barriers (and whether they varied over time and geographic locations), and to identify associations between nurses' reported barriers and reported research use.

Methods

Medline (1991 to September 2009) and CINHAL (1991 to September 2009) were searched for published research, and ProQuest® digital dissertations were searched for unpublished dissertations using the BARRIERS scale. Inclusion criteria were: studies using the BARRIERS scale in its entirety and where the sample was nurses. Two authors independently assessed the study quality and extracted the data. Descriptive and inferential statistics were used.

Results

Sixty-three studies were included, with most using a cross-sectional design. Not one study used the scale for tailoring interventions to overcome identified barriers. The main barriers reported were related to the setting, and the presentation of research findings. Overall, identified barriers were consistent over time and across geographic locations, despite varying sample size, response rate, study setting, and assessment of study quality. Few studies reported associations between reported research use and perceptions of barriers to research utilization.

Conclusions

The BARRIERS scale is a nonspecific tool for identifying general barriers to research utilization. The scale is reliable as reflected in assessments of internal consistency. The validity of the scale, however, is doubtful. There is no evidence that it is a useful tool for planning implementation interventions. We recommend that no further descriptive studies using the BARRIERS scale be undertaken. Barriers need to be measured specific to the particular context of implementation and the intended evidence to be implemented.
Tetrabenazine is neuroprotective in Huntington's disease mice
Authors: Wang Hongyu , Chen Xi , Li Yuemei , Tang Tie-Shan , Bezprozvanny Ilya
Published: April 2010

Background

Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in Huntingtin protein (Htt). PolyQ expansion in Httexp causes selective degeneration of striatal medium spiny neurons (MSN) in HD patients. A number of previous studies suggested that dopamine signaling plays an important role in HD pathogenesis. A specific inhibitor of vesicular monoamine transporter (VMAT2) tetrabenazine (TBZ) has been recently approved by Food and Drug Administration for treatment of HD patients in the USA. TBZ acts by reducing dopaminergic input to the striatum.

Results

In previous studies we demonstrated that long-term feeding with TBZ (combined with L-Dopa) alleviated the motor deficits and reduced the striatal neuronal loss in the yeast artificial chromosome transgenic mouse model of HD (YAC128 mice). To further investigate a potential beneficial effects of TBZ for HD treatment, we here repeated TBZ evaluation in YAC128 mice starting TBZ treatment at 2 months of age ("early" TBZ group) and at 6 months of age ("late" TBZ group). In agreement with our previous studies, we found that both "early" and "late" TBZ treatments alleviated motor deficits and reduced striatal cell loss in YAC128 mice. In addition, we have been able to recapitulate and quantify depression-like symptoms in TBZ-treated mice, reminiscent of common side effects observed in HD patients taking TBZ.

Conclusions

Our results further support therapeutic value of TBZ for treatment of HD but also highlight the need to develop more specific dopamine antagonists which are less prone to side-effects.
Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma
Authors: Liu Huiqing , Brannon Angela R , Reddy Anupama R , Alexe Gabriela , Seiler Michael W , Arreola Alexandra , Oza Jay H , Yao Ming , Juan David , Liou Louis S , Ganesan Shridar , Levine Arnold J , Rathmell WK , Bhanot Gyan V
Published: April 2010

Background

MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation.

Results

We describe a simple method to identify direct mRNA targets of microRNA dysregulated in cancers from expression level measurements in patient matched tumor/normal samples. The word "direct" is used here in a strict sense to: a) represent mRNA which have an exact seed sequence match to the microRNA in their 3'UTR, b) the seed sequence match is strictly conserved across mouse, human, rat and dog genomes, c) the mRNA and microRNA expression levels can distinguish tumor from normal with high significance and d) the microRNA/mRNA expression levels are strongly and significantly anti-correlated in tumor and/or normal samples. We apply and validate the method using clear cell Renal Cell Carcinoma (ccRCC) and matched normal kidney samples, limiting our analysis to mRNA targets which undergo degradation of the mRNA transcript because of a perfect seed sequence match. Dysregulated microRNA and mRNA are first identified by comparing their expression levels in tumor vs normal samples. Putative dysregulated microRNA/mRNA pairs are identified from these using seed sequence matches, requiring that the seed sequence be conserved in human/dog/rat/mouse genomes. These are further pruned by requiring a strong anti-correlation signature in tumor and/or normal samples. The method revealed many new regulations in ccRCC. For instance, loss of miR-149, miR-200c and mir-141 causes gain of function of oncogenes (KCNMA1, LOX), VEGFA and SEMA6A respectively and increased levels of miR-142-3p, miR-185, mir-34a, miR-224, miR-21 cause loss of function of tumor suppressors LRRC2, PTPN13, SFRP1, ERBB4, and (SLC12A1, TCF21) respectively. We also found strong anti-correlation between VEGFA and the miR-200 family of microRNA: miR-200a*, 200b, 200c and miR-141. Several identified microRNA/mRNA pairs were validated on an independent set of matched ccRCC/normal samples. The regulation of SEMA6A by miR-141 was verified by a transfection assay.

Conclusions

We describe a simple and reliable method to identify direct gene targets of microRNA in any cancer. The constraints we impose (strong dysregulation signature for microRNA and mRNA levels between tumor/normal samples, evolutionary conservation of seed sequence and strong anti-correlation of expression levels) remove spurious matches and identify a subset of robust, tissue specific, functional mRNA targets of dysregulated microRNA.
CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo
Authors: He Songbing , Wang Liang , Wu Yugang , Li Dechun , Zhang Yanyun
Published: April 2010

Background

To investigate whether dendritic cell (DC) precursors, recruited by injection of chemokine ligand 3 (CCL3) and CCL20, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1) ex vivo and in vivo.

Methods

B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR). For adenoviral (Ad)-mediated gene transduction, cultured F4/80-B220-CD11c+ cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-γ production was determined with an INF-γ ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines.

Results

F4/80-B220-CD11c+ cell numbers increased after CCL3 and CCL20 injection. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-γ ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (P < 0.05). Kaplan-Meier survival curves showed that survival of the experimental group mice was significantly longer than the control groups (P < 0.05). In addition, MAGE-1-transduced DCs were also a therapeutic benefit on an established metastatic tumor, resulting in a tremendous decrease in the number of pulmonary metastatic foci.

Conclusions

CCL3 and CCL20-recruited DCs modified by adenovirus-trasnsduced, tumor-associated antigen, MAGE-1, can stimulate anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.
Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats
Authors: Priyadarshani Anjali , Chuttani Krishna , Mittal Gaurav , Bhatnagar Aseem
Published: April 2010

Background

Noscapine, an alkaloid fromPapaver somniferum, widely used as an antitussive, is being clinically studied in the treatment of polycystic ovary syndrome (PCOS) and a few other cancers primarily because of its anti-angiogenesis properties. With the advent of diverse application of noscapine, we sought to determine whether the radiolabeling method can be useful in studying uptake and kinetics of the molecule in-vivo. Specific objectives of this study were to radiolabel noscapine with Technetium-99m (Tc-99m), to determine its organ biodistribution in rat model and study its uptake kinetics in PCOS model.

Methods

A method for radiolabeling noscapine with Tc-99m was standardized using stannous reduction method and its in vitro and in vivo stability parameters were studied. The radiopharmaceutical was also evaluated for blood kinetics and biodistribution profile. An animal model of PCOS was created by using antiprogesterone RU486 and uptake of99mTc-noscapine in normal and PCOS ovaries was compared using gamma scintigraphy.

Results

Noscapine hydrochloride was successfully radiolabeled with Tc-99m with high labeling efficiency and in vitro stability. Most of the blood clearance of the drug (80%) took place in first hour after intravascular injection with maximum accumulation being observed in liver, spleen, kidney followed by the ovary. At 4 hours post injection, radiolabeled complex accumulation doubled in PCOS ovaries in rats (0.9 ± 0.03% ID/whole organ) compared to normal cyclic rats (0.53 ± 0.01% ID/whole organ). This observation was further strengthened by scintigraphic images of rats taken at different time intervals (1 h, 2 h, 4 h, and 24 h) where SPECT images suggested discrete accumulation in the PCOS ovaries.

Conclusion

Through our study we report direct radiolabeling of noscapine and its biodistribution in various organs and specific uptake in PCOS that may show its utility for imaging ovarian pathology. The increased ovarian uptake in PCOS may be related to its receptor binding suggesting possible role of99mTc-noscapine in PCOS diagnostics and therapeutics.
Phylogenetic detection of numerous gene duplications shared by animals, fungi and plants
Authors: Zhou Xiaofan , Lin Zhenguo , Ma Hong
Published: April 2010

Background

Gene duplication is considered a major driving force for evolution of genetic novelty, thereby facilitating functional divergence and organismal diversity, including the process of speciation. Animals, fungi and plants are major eukaryotic kingdoms and the divergences between them are some of the most significant evolutionary events. Although gene duplications in each lineage have been studied extensively in various contexts, the extent of gene duplication prior to the split of plants and animals/fungi is not clear.

Results

Here, we have studied gene duplications in early eukaryotes by phylogenetic relative dating. We have reconstructed gene families (with one or more orthogroups) with members from both animals/fungi and plants by using two different clustering strategies. Extensive phylogenetic analyses of the gene families show that, among nearly 2,600 orthogroups identified, at least 300 of them still retain duplication that occurred before the divergence of the three kingdoms. We further found evidence that such duplications were also detected in some highly divergent protists, suggesting that these duplication events occurred in the ancestors of most major extant eukaryotic groups.

Conclusions

Our phylogenetic analyses show that numerous gene duplications happened at the early stage of eukaryotic evolution, probably before the separation of known major eukaryotic lineages. We discuss the implication of our results in the contexts of different models of eukaryotic phylogeny. One possible explanation for the large number of gene duplication events is one or more large-scale duplications, possibly whole genome or segmental duplication(s), which provides a genomic basis for the successful radiation of early eukaryotes.
On seismic interferometry, the generalized optical theorem, and the scattering matrix of a point scatterer
Authors: Wapenaar Kees , Slob Evert , Snieder Roel
Published: April 2010

We have analyzed the far-field approximation of the Green’s function representation for seismic interferometry. By writing each of the Green’s functions involved in the correlation process as a superposition of a direct wave and a scattered wave, the Green’s function representation is rewritten as a superposition of four terms. When the scattered waves are modeled with the Born approximation, it appears that a three-term approximation of the Green’s function representation (omitting the term containing the crosscorrelation of the scattered waves) yields a nearly exact retrieval, whereas the full four-term expression leads to a significant nonphysical event. This is because the Born approximation does not conserve energy and therefore is an insufficient model to explain all aspects of seismic interferometry. We use the full four-term expression of the Green’s function representation to derive the generalized optical theorem. Unlike other recent derivations, which use stationary phase analysis, our derivation uses reciprocity theory. From the generalized optical theorem, we derive the nonlinear scattering matrix of a point scatterer. This nonlinear model accounts for primary and multiple scattering at the point scatterer and conforms with well-established scattering theory of classical waves. The model is essential to explain fully the results of seismic interferometry, even when it is applied to the response of a single point scatterer. The nonlinear scattering matrix also has implications for modeling, inversion, and migration.
Spectral balancing GPR data using time-variant bandwidth in the t-f domain
Authors: Economou Nikos , Vafidis Antonis
Published: April 2010

Ground-penetrating radar (GPR) sections encounter a resolution reduction with depth because, for electromagnetic (EM) waves propagating in the subsurface, attenuation is typically more pronounced at higher frequencies. To correct for these effects, we have applied a spectral balancing technique, using the S-transform (ST). This signal-processing technique avoids the drawbacks of inverse [Formula: see text] filtering techniques, namely, the need for estimation of the attenuation factor [Formula: see text] from the GPR section and instability caused by scattering effects that result from methods of dominant frequency-dependent estimation of [Formula: see text]. The method designs and applies a gain in the time-frequency ([Formula: see text]) domain and involves the selection of a time-variant bandwidth to reduce high-frequency noise. This method requires a reference amplitude spectrum for spectral shaping. It performs spectral balancing, which works efficiently for GPR data when it is applied in very narrow time windows. Furthermore, we have found that spectral balancing must be applied prior to deconvolution, instead of being an alternative technique.
Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication
Authors: Vickers Andrew , Cronin Angel , Roobol Monique , Savage Caroline , Peltola Mari , Pettersson Kim , Scardino Peter T. , Schröder Fritz , Lilja Hans
Published: April 2010

Purpose

We previously reported that a panel of four kallikrein forms in blood—total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)—can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.

Patients and Methods

The study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (≥ 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.

Results

Addition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.

Conclusion

We have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.
Intensity-Modulated Chemoradiotherapy Aiming to Reduce Dysphagia in Patients With Oropharyngeal Cancer: Clinical and Functional Results
Authors: Feng Felix Y. , Kim Hyungjin M. , Lyden Teresa H. , Haxer Marc J. , Worden Francis P. , Feng Mary , Moyer Jeffrey S. , Prince Mark E. , Carey Thomas E. , Wolf Gregory T. , Bradford Carol R. , Chepeha Douglas B. , Eisbruch Avraham
Published: April 2010

Purpose

To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia.

Patients and Methods

This was a prospective study of weekly chemotherapy (carboplatin dosed at one times the area under the curve [AUC, AUC 1] and paclitaxel 30 mg/m2) concurrent with IMRT aiming to spare noninvolved parts of the swallowing structures: pharyngeal constrictors, glottic and supraglottic larynx, and esophagus as well as the oral cavity and major salivary glands. Swallowing was assessed by patient-reported Swallowing and Eating Domain scores, observer-rated scores, and videofluoroscopy (VF) before therapy and periodically after therapy through 2 years.

Results

Overall, 73 patients with stages III to IV OPC participated. At a median follow-up of 36 months, 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. All measures of dysphagia worsened soon after therapy; observer-rated and patient-reported scores recovered over time, but VF scores did not. At 1 year after therapy, observer-rated dysphagia was absent or minimal (scores 0 to 1) in all patients except four: one who was feeding-tube dependent and three who required soft diet. From pretherapy to 12 months post-therapy, the Swallowing and Eating Domain scores worsened on average (± standard deviation) by 10 ± 21 and 13 ± 19, respectively (on scales of 0 to 100), and VF scores (on scale of 1 to 7) worsened from 2.9 ± 1.5 (mild dysphagia) to 4.1 ± 0.9 (mild/moderate dysphagia).

Conclusion

Chemoradiotherapy with IMRT aiming to reduce dysphagia can be performed safely for OPC and has high locoregional tumor control rates. On average, long-term patient-reported, observer-rated, and objective measures of swallowing were only slightly worse than pretherapy measures, representing potential improvement compared with previous studies.
Incidence and Clinical Complications of Myelodysplastic Syndromes Among United States Medicare Beneficiaries
Authors: Goldberg Stuart L. , Chen Er , Corral Mitra , Guo Amy , Mody-Patel Nikita , Pecora Andrew L. , Laouri Marianne
Published: April 2010

Purpose

To determine the incidence and complications of myelodysplastic syndromes (MDS) among Medicare beneficiaries.

Methods

Retrospective review of 2003 Medicare Standard Analytic Files utilizing International Classification of Diseases for Oncology ninth edition CM code 238.7 to identify new MDS patients, with 3-year follow-up.

Results

Among 1,394,343 individuals in Medicare Standard Analytic Files age ≥ 65 years, 162 per 100,000 were coded as newly diagnosed MDS during 2003 yielding a calculated 45,000 new cases in the United States Medicare ≥ 65 years population. Patients with MDS were older (median age, 77 years), and over-represented by males. Among patients with MDS diagnosed during first quarter of 2003, 73.2% suffered cardiac-related events during 3-year follow-up, which exceeded the Medicare population (54.5%; P < .01) even when age adjusted (odds ratio, 2.10; P < .01). Significant increases in prevalence of diabetes (40.0% v 33.1%), dyspnea (49.4% v 28.5%), hepatic diseases (0.8% v 0.2%), and infections (sepsis: 22.5% v 6.1%) were noted in MDS (all P < .01) compared with the Medicare population. Patients with MDS requiring RBC transfusions had greater prevalence of these comorbidities. Acute myeloid leukemia developed within 3 years in 9.6%, with increased transformation among transfused (24.6%; P < .001). The 3-year Kaplan-Meier age-adjusted survival for MDS was 60.0%, which was significantly lower than the Medicare population (84.7%; hazard ratio, 3.08; P < .001), and mortality was further increased among transfused MDS (P < .01). In 2003, median payment for MDS was $16,181, compared to $1,575 for the Medicare population (P < .001).

Conclusion

MDS is a common hematologic malignancy of the elderly, which places patients at risk for comorbid conditions. Transfusion dependency identifies patients with MDS at additional increased risk of organ impairment and shortened survival.
Functional Activity of the OCT-1 Protein Is Predictive of Long-Term Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib
Authors: White Deborah L. , Dang Phuong , Engler Jane , Frede Amity , Zrim Stephanie , Osborn Michael , Saunders Verity A. , Manley Paul W. , Hughes Timothy P.
Published: April 2010

Purpose

Organic cation transporter-1 (OCT-1) activity (OA), a measure of the OCT-1–mediated influx of imatinib into CML mononuclear cells (MNCs), is predictive of major molecular response (MMR) at 12 and 24 months in patients with untreated CML. We now report the impact of OA on loss of response, disease transformation, and survival after 5 years of imatinib.

Patients and Methods

OA is defined as the difference in intracellular concentration of carbon-14–imatinib with and without OCT-1 inhibition. OA was measured in blood from 56 patients with untreated chronic-phase CML.

Results

More patients who had high OA (ie, > median OA value) achieved MMR by 60 months compared with patients who had low OA (89% v 55%; P = .007). A low OA was associated with a significantly lower overall survival (87% v 96%; P = .028) and event-free survival (EFS; 48% v 74%; P = .03) as well as a higher kinase domain mutation rate (21% v 4%; P = .047). These differences were highly significant in patients who averaged less than 600 mg/d of imatinib in the first 12 months but were not significant in patients averaging ≥ 600 mg/d. Patients with very low OA (ie, quartile 1) were the only group who developed leukemic transformation (21% in quartile 1 v 0% in all other quartiles; P = .002).

Conclusion

Measurement of OA pretherapy is a predictor for the long-term risk of resistance and transformation in patients with imatinib-treated CML. Early dose-intensity may reduce the negative prognostic impact of low OA. We propose that OA could be used to individualize dosage strategies for patients with CML to maximize molecular response and optimize long-term outcome.
High Expression of the Very Late Antigen-4 Integrin Independently Predicts Reduced Risk of Relapse and Improved Outcome in Pediatric Acute Myeloid Leukemia: A Report From the Children's Oncology Group
Authors: Walter Roland B. , Alonzo Todd A. , Gerbing Robert B. , Ho Phoenix A. , Smith Franklin O. , Raimondi Susana C. , Hirsch Betsy A. , Gamis Alan S. , Franklin Janet L. , Hurwitz Craig A. , Loken Michael R. , Meshinchi Soheil
Published: April 2010

Purpose

To evaluate the prognostic significance of the integrin cell adhesion molecule very late antigen-4 (VLA-4) in acute myeloid leukemia (AML).

Patients and Methods

We prospectively quantified VLA-4 expression in 216 patients enrolled onto COG-AAML03P1 by flow cytometry and correlated expression levels with disease characteristics and clinical outcome.

Results

VLA-4 mean fluorescence intensity (MFI) varied 35-fold (range, 30 to 1,110; median, 219.5). High VLA-4 expression (> median MFI), compared with low expression, was associated with younger age (7.1 v 12.1 years, respectively; P < .001), lower FLT3 internal tandem duplication prevalence (4% v 21%, respectively; P < .001), and higher likelihood of extramedullary disease (16% v 5%, respectively; P = .013). In low- and high-expression groups, rates of remission (89% v 80%, respectively; P = .137) and minimal residual disease (29% v 25%, respectively; P = .700) were similar. Patients with low VLA-4 expression, compared with high expression, had a higher relapse rate (RR; 44% ± 10% v 24% ± 9%, respectively; P = .011) and lower disease-free survival (DFS; 48% ± 11% v 67% ± 10%, respectively; P = .023) after 3 years. Multivariate analyses showed that low VLA-4 expression was an independent adverse prognostic factor for DFS (hazard ratio [HR] = 1.98; P = .038) and RR (HR = 2.77; P = .009). Subgroup analyses indicated that the prognostic role of VLA-4 expression was most prominent in patients with standard-risk AML, in whom low VLA-4 expression was associated with inferior DFS (34% ± 16% v 69% ± 14% for high expression; P = .011) and higher RR (61% ± 16% v 26% ± 14% for high expression; P = .009). A similar trend was seen in low-risk but not high-risk patients.

Conclusion

High VLA-4 expression is associated with better clinical outcome in pediatric AML and is an independent predictor of relapse that may refine our abilities to stratify patients without identifiable cytogenetic or molecular risk factors.
Results of Microsurgical Extra-Intracranial Arterial Bypass in the Treatment of Cerebral Ischemia
Authors: Yasargil Gazi M. , Yonekawa Yasuhiro
Published: April 2010

The authors report the operative and follow-up results (3 months to 9 years) of 86 consecutive extra-intracranial bypass operations on 84 patients with cerebral ischemia, emphasizing both the prophylactic role of the operation in preventing further catastrophic cerebral ischemia, and the low morbidity and mortality of the operation.
The Treatment of Intracranial Aneurysms by Injection with a Tissue Adhesive
Authors: Sheptak Peter E. , Zanetti Paul H. , Susen Anthony F.
Published: April 2010

The authors have developed a technique of occluding intracranial aneurysms by the direct injection of a tissue adhesive. Previous work in our laboratory had revealed the unusual intravascular characteristics and physiological properties of isobutyl-2-cyanoacrylate (IBC). These findings had indicated the feasibility of utilizing IBC in the treatment of intracranial aneurysms by its direct injection. We have now treated twenty patients by this method. Eighteen aneurysms were injected during open craniotomy and two were treated by closed stereotactic injection utilizing electronic radiography. Follow-up data, ranging from 1 to 6 years after operation, are available on these patients. Sixteen patients (80% of the series) have had good to excellent results. Our experience and the application of this technique as a potential tool in the treatment of intracranial aneurysms are discussed.
Cranial Computed Tomographic Demonstration of Intracranial Penetration by an Orbital Foreign Body
Authors: Lunsford Dade L. , Woodford Jack , Drayer Burton P.
Published: April 2010

A 9-year-old boy suffered intracerebral penetration by a stick driven into his right orbit. Diagnosis was obtained by cranial computed tomography (CT), and this test directed appropriate immediate surgical intervention. Combined orbital exploration and craniotomy was followed by a gratifying recovery. The importance of CT in orbital and possible intracranial trauma is stressed.
Dysregulation of cell-to-cell connectivity and stomatal patterning by loss-of-function mutation inArabidopsis CHORUS(GLUCAN SYNTHASE-LIKE 8)
Authors: Guseman Jessica M. , Lee Jin Suk , Bogenschutz Naomi L. , Peterson Kylee M. , Virata Rebecca E. , Xie Bo , Kanaoka Masahiro M. , Hong Zonglie , Torii Keiko U.
Published: April 2010

Patterning of stomata, valves on the plant epidermis, requires the orchestrated actions of signaling components and cell-fate determinants. To understand the regulation of stomatal patterning, we performed a genetic screen using a background that partially lacks stomatal signaling receptors. Here, we report the isolation and characterization of chorus (chor), which confers excessive proliferation of stomatal-lineage cells mediated by SPEECHLESS (SPCH). chor breaks redundancy among three ERECTA family genes and strongly enhances stomatal patterning defects caused by loss-of-function in TOO MANY MOUTHS. chor seedlings also exhibit incomplete cytokinesis and growth defects, including disruptions in root tissue patterning and root hair cell morphogenesis. CHOR encodes a putative callose synthase, GLUCAN SYNTHASE-LIKE 8 (GSL8), that is required for callose deposition at the cell plate, cell wall and plasmodesmata. Consistently, symplastic macromolecular diffusion between epidermal cells is significantly increased in chor, and proteins that do not normally move cell-to-cell, including a fluorescent protein-tagged SPCH, diffuse to neighboring cells. Such a phenotype is not a general trait caused by cytokinesis defects. Our findings suggest that the restriction of symplastic movement might be an essential step for the proper segregation of cell-fate determinants during stomatal development.
Hysteresis-loop representation for strain energy calculation and fatigue assessment
Authors: Scott-Emuakpor O , George T , Cross C , Shen M-H Herman
Published: April 2010

Improvements have been made to the cyclic strain energy density expression used in a fatigue life prediction method. The theory behind the prediction method is based on the understanding that the same amount of strain energy is dissipated during a monotonic fracture and a cyclic fatigue process. From this understanding, the failure cycle for a fatigue process can be determined by dividing monotonic strain energy by the average strain energy per cycle. Though this technique has been shown to be acceptable, it needs to be improved to account from the experimentally observed increase in the strain energy per cycle as the loading cycles approach fatigue. In order to improve the fatigue life prediction technique, experimental strain energy density per cycle is observed during the fatigue process of Aluminium 6061-T6 (Al 6061-T6) specimens. The results show exponential change in the strain energy density through the first 20 per cent and the last 30 per cent of the total failure cycles. The results lead to a new representation of strain energy density per cycle, which leads to an improved fatigue life prediction method. A comparison is made between the improved prediction method and experimental fatigue results. The comparison result validates the precision of the new hysteresis-loop representation.
Impact, penetration, and perforation of a bonded carbon-fibre-reinforced plastic composite panel by a high-velocity steel sphere: An experimental study
Authors: Hazell P J , Appleby-Thomas G J , Kister G
Published: April 2010

In this work, the response of a bonded carbon-fibre-reinforced plastic composite panel, which had been manufactured by bonding two laminates together, to impact, penetration, and perforation by a high-velocity steel sphere has been studied. The response of a relatively thick (about 12 mm) laminate has been compared with similar data from previous work by Hazell et al. where relatively thin monolithic laminates were impacted by the same type of projectile. It was found that the ballistic performance of the system was increased over the impact energy range of interest when compared with these similar, relatively thin composite laminates. Furthermore, both the energy absorbed per unit thickness of laminate and the level of damage as measured by a C-Scan system when the panels were perforated at normal incidence and oblique incidence were similar. This raises the prospect of reducing experimental testing at oblique angles, if the behaviour at normal incidence is known.
Identification of Poisson's ratios of standard and auxetic low-density polymeric foams from full-field measurements
Authors: Pierron F
Published: April 2010

This exploratory paper presents some preliminary results on the use of full-field deformation measurements on low-density polymeric foams to identify the evolution of Poisson's ratio with compressive strain. Two types of foams were tested: a standard low-density polyurethane foam and an auxetic foam manufactured from a similar precursor. Two-dimensional digital image correlation was used to measure the strain field at the specimens' surfaces. Then, Poisson's ratios were identified using a dedicated inverse method called the virtual fields method (VFM) and the results compared with the standard approaches. The results illustrate the advantages of the VFM compared to the standard procedure. It was also found that for the standard foam, very strong localization effects resulted in biased Poisson's ratio evaluation. It was shown that this could be corrected by taking into account these localization effects thanks to the full-field information.
Position Tracking Control of a Flexible Beam Using a Piezoceramic Actuator with a Hysteretic Compensator
Authors: Nguyen P-B , Sohn J W , Choi S-B
Published: April 2010

This article presents position tracking control of a flexible beam using a piezoelectric actuator. This is achieved by implementing both a feedforward hysteretic compensator of the actuator and a proportional-integral-derivative (PID) feedback controller. The Preisach model is adopted to develop the feedforward hysteretic compensator. In the design of the compensator, estimated displacement of the piezoceramic actuator is used based on the limiting triangle database that results from collecting data of the main reversal curve and the first-order ascending curves. Modal parameters of the flexible beam, such as natural frequency, are obtained using a finite element method. Experimental implementation is conducted for position tracking control and performance comparison is made among an open-loop feedforward compensator, a PID feedback controller without considering the effect of hysteresis, and a PID feedback controller integrated with the feedforward hysteretic compensator.
A New Method for Analysing Large Elasto-Plastic Deformations of a Thin Cosserat Shell
Authors: Ghassemi A , Shahidi A , Farzin M
Published: April 2010

One of the best approaches for modelling the large deformation of shells is the Cosserat surface; however, the finite-element implementation of this model suffers from membrane and shear locking, especially for very thin shells. If the director vector is constrained to remain perpendicular to the mid-surface, during deformation, locking will be prevented. This constraint is in fact a limiting analysis of the Cosserat theory in which Kirchhoff's hypothesis is enforced. This has been considered for the first time. Simo's plastic approach is modified to implement the constrained director. This model includes both kinematic and isotropic hardening behaviours. A consistent elasto-plastic tangent modular matrix is extracted. Numerical solution is performed by interpolation of displacement on the whole domain, and a hierarchical finite-element scheme is developed. The principle of virtual work is used to obtain the weak form of the governing differential equations and the material and geometric stiffness matrices are derived through a linearization process. The validity and the accuracy of the method are illustrated by numerical examples.
Robust Design Optimization of Gear Parameters for a Wind Turbine Using Interval Analysis
Authors: Dong R , Sun W , Xu H
Published: April 2010

A robust design optimization method is suggested to optimize the system parameters of a gear transmission for a wind turbine with minimum sensitivity of fatigue strength to variations in uncertain application factor, dynamic load coefficient, material property parameters, and other coefficients representing unknown working condition. Interval numbers are employed to model the uncertainties by which only the upper and lower bounds are needed. Based on interval mathematics, the original real-valued objective and constraint functions are replaced by the interval-valued functions, which directly represent the variation bounds of the new functions under uncertainty. The single-objective function is converted into two-objective functions for minimizing the mean value and the variation, and the constraint functions are reformulated with the acceptable robustness level, resulting in a bi-level mathematical model. The optimization results of gear parameter demonstrate the validity and feasibility of the presented method.
Investigation into the Dynamics of Layered and Jointed Cantilevered Beams
Authors: Mohanty R C , Nanda B K
Published: April 2010

Damping occurring at the joints due to interfacial relative motion is the major source of inherent damping in fabricated structures. In the present investigation, the dynamic analysis of layered cantilever beams jointed with rivets was carried out using the finite element approach for the Euler—Bernoulli beam model. The solution is based on one-dimensional beam elements, with each element consisting of two nodes having two degrees of freedom (i.e. transverse displacement and rotation) at each node. The cubic shape functions are considered for the transverse vibration of the beam in terms of nodal variables. The stiffness and mass matrices are evaluated from the bending strain energy and kinetic energy of the beam, respectively, which are further used to determine the natural frequency and mode shapes by modal analysis. The damping capacity of the cantilever specimens was computed using the energy approach. Experiments were conducted for validating the numerical results. The results establish that the damping capacity of built-up structures having lower beam thickness ratio and higher cantilever length can be improved substantially using larger diameter rivets at lower amplitude of excitation.
Reduction of Solid-Particle Erosion on the Control-Stage Nozzle of a Steam Turbine through Improved End-Wall Contouring
Authors: Wang S-S , Mao J-R , Liu G-W , Feng Z-P
Published: April 2010

The iron oxide scales exfoliated from the inner wall of a boiler tube and a main steam pipe is known to cause solid-particle erosion on the control-stage nozzle. A combined experimental and numerical investigation was conducted to explore the optimization method of end-wall contouring for reducing the nozzle's erosion damage most effectively. The results indicate that increasing the end-wall contraction ratio and (or) decreasing the distance between the starting point of end-wall contouring and the trailing edge can significantly reduce the erosion-induced weight-loss of the nozzle, and can slightly improve the nozzle efficiency, irrespective of the variation in the particles size distribution and the aerodynamic parameters of a steam turbine. A main reason of erosion reduction is that the movement of loading towards the rear of the nozzle cascade caused by these contoured end walls has reduced the incident velocity of particles. In this study, the weight-loss of the nozzle was reduced by 40—50 per cent, and the nozzle efficiency was improved by 0.4—0.5 per cent by improving the end-wall contouring of the nozzle according to the methods mentioned above.