bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Kinase CK2 Protects Multiple Myeloma Cells from ER Stress–Induced Apoptosis and from the Cytotoxic Effect of HSP90 Inhibition through Regulation of the Unfolded Protein Response
Authors: Manni Sabrina , Brancalion Alessandra , Tubi Laura Quotti , Colpo Anna , Pavan Laura , Cabrelle Anna , Ave Elisa , Zaffino Fortunato , Di Maira Giovanni , Ruzzene Maria , Adami Fausto , Zambello Renato , Pitari Maria Rita , Tassone Pierfrancesco , Pinna Lorenzo A. , Gurrieri Carmela , Semenzato Gianpietro , Piazza Francesco 
Published: February 2012

AbstractPurpose: Protein kinase CK2 promotes multiple myeloma cell growth by regulating critical signaling pathways. CK2 also modulates proper HSP90-dependent client protein folding and maturation by phosphorylating its co-chaperone CDC37. Because the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is central in myeloma pathogenesis, we tested the hypothesis that the CK2/CDC37/HSP90 axis could be involved in UPR in myeloma cells.Experimental Design: We analyzed CK2 activity upon ER stress, the effects of its inactivation on the UPR pathways and on ER stress–induced apoptosis. The consequences of CK2 plus HSP90 inhibition on myeloma cell growth in vitro and in vivo and CK2 regulation of HSP90-triggered UPR were determined.Results: CK2 partly localized to the ER and ER stress triggered its kinase activity. CK2 inhibition reduced the levels of the ER stress sensors IRE1α and BIP/GRP78, increased phosphorylation of PERK and EIF2α, and enhanced ER stress–induced apoptosis. Simultaneous inactivation of CK2 and HSP90 resulted in a synergic anti-myeloma effect (combination index = 0.291) and in much stronger alterations of the UPR pathways as compared with the single inhibition of the two molecules. Cytotoxicity from HSP90 and CK2 targeting was present in a myeloma microenvironment model, on plasma cells from patients with myeloma and in an in vivo mouse xenograft model. Mechanistically, CK2 inhibition led to a reduction of IRE1α/HSP90/CDC37 complexes in multiple myeloma cells.Conclusions: Our results place CK2 as a novel regulator of the ER stress/UPR cascades and HSP90 function in myeloma cells and offer the groundwork to design novel combination treatments for this disease. Clin Cancer Res; 18(7); 1888–900. ©2012 AACR.
Connexin 47 Mutations Increase Risk for Secondary Lymphedema Following Breast Cancer Treatment
Authors: Finegold David N. , Baty Catherine J. , Knickelbein Kelly Z. , Perschke Shelley , Noon Sarah E. , Campbell Diana , Karlsson Jenny M. , Huang Diana , Kimak Mark A. , Lawrence Elizabeth C. , Feingold Eleanor , Meriney Stephen D. , Brufsky Adam M. , Ferrell Robert E. 
Published: February 2012

Abstract
Purpose: Secondary lymphedema is a frequent complication of breast cancer associated with surgery, chemotherapy, or radiation following breast cancer treatment. The potential contribution of genetic susceptibility to risk of developing secondary lymphedema following surgical trauma, radiation, and other tissue insults has not been studied.
Experimental Design: To determine whether women with breast cancer and secondary lymphedema had mutations in candidate lymphedema genes, we undertook a case–control study of 188 women diagnosed with breast cancer recruited from the University of Pittsburgh Breast Cancer Program (http://www.upmccancercenter.com/breast/index.cfm) between 2000 and 2010.
Candidate lymphedema genes, GJC2 (encoding connexin 47 [Cx47]), FOXC2, HGF, MET, and FLT4 (encoding VEGFR3), were sequenced for mutation. Bioinformatics analysis and in vitro functional assays were used to confirm significance of novel mutations.
Results: Cx47 mutations were identified in individuals having secondary lymphedema following breast cancer treatment but not in breast cancer controls or normal women without breast cancer. These novel mutations are dysfunctional as assessed through in vitro assays and bioinformatics analysis and provide evidence that altered gap junction function leads to lymphedema.
Conclusions: Our findings challenge the view that secondary lymphedema is solely due to mechanical trauma and support the hypothesis that genetic susceptibility is an important risk factor for secondary lymphedema. A priori recognition of genetic risk (i) raises the potential for early detection and intervention for a high-risk group and (ii) allows the possibility of altering surgical approach and/or chemo- and radiation therapy, or direct medical treatment of secondary lymphedema with novel connexin-modifying drugs. Clin Cancer Res; 18(8); 2382–90. ©2012 AACR.
Antarctic Sea Ice Climatology, Variability, and Late Twentieth-Century Change in CCSM4
Authors: Landrum Laura , Holland Marika M. , Schneider David P. , Hunke Elizabeth 
Published: February 2012

Abstract
A preindustrial control run and an ensemble of twentieth-century integrations of the Community Climate System Model, version 4 (CCSM4), are evaluated for Antarctic sea ice climatology, modes of variability, trends, and covariance with related physical variables such as surface temperature and sea level pressure. Compared to observations, the mean ice cover is too extensive in all months. This is in part related to excessively strong westerly winds over ~50°–60°S, which drive a large equatorward meridional ice transport and enhanced ice growth near the continent and also connected with a cold bias in the Southern Ocean. In spite of these biases in the climatology, the model’s sea ice variability compares well to observations. The leading mode of austral winter sea ice concentration exhibits a dipole structure with anomalies of opposite sign in the Atlantic and Pacific sectors. Both the El Niño–Southern Oscillation and the southern annular mode (SAM) project onto this mode. In twentieth-century integrations, Antarctic sea ice area exhibits significant decreasing annual trends in all six ensemble members from 1950 to 2005, in apparent contrast to observations that suggest a modest ice area increase since 1979. Two ensemble members show insignificant changes when restricted to 1979–2005. The ensemble mean shows a significant increase in the austral summer SAM index over 1960–2005 and 1979–2005 that compares well with the observed SAM trend. However, Antarctic warming and sea ice loss in the model are closely connected to each other and not to the trend in the SAM.
The Impact of Rainfall Error Characterization on the Estimation of Soil Moisture Fields in a Land Data Assimilation System
Authors: Maggioni Viviana , Reichle Rolf H. , Anagnostou Emmanouil N. 
Published: February 2012

Abstract
This study presents a numerical experiment to assess the impact of satellite rainfall error structure on the efficiency of assimilating near-surface soil moisture observations. Specifically, the study contrasts a multidimensional satellite rainfall error model (SREM2D) to a simpler rainfall error model (CTRL) currently used to generate rainfall ensembles as part of the ensemble-based land data assimilation system developed at the NASA Global Modeling and Assimilation Office. The study is conducted in the Oklahoma region using rainfall data from a NOAA multisatellite global rainfall product [the Climate Prediction Center (CPC) morphing technique (CMORPH)] and the National Weather Service rain gauge–calibrated radar rainfall product [Weather Surveillance Radar-1988 Doppler (WSR-88D)] representing the “uncertain” and “reference” model rainfall forcing, respectively. Soil moisture simulations using the Catchment land surface model (CLSM), obtained by forcing the model with reference rainfall, are randomly perturbed to represent satellite retrieval uncertainty, and assimilated into CLSM as synthetic near-surface soil moisture observations. The assimilation estimates show improved performance metrics, exhibiting higher anomaly correlation coefficients (e.g., ~0.79 and ~0.90 in the SREM2D nonassimilation and assimilation experiments for root zone soil moisture, respectively) and lower root-mean-square errors (e.g., ~0.034 m3 m−3 and ~0.024 m3 m−3 in the SREM2D nonassimilation and assimilation experiments for root zone soil moisture, respectively). The more elaborate rainfall error model in the assimilation system leads to slightly improved assimilation estimates. In particular, the relative enhancement due to SREM2D over CTRL is larger for root zone soil moisture and in wetter rainfall conditions.
Accounting for Skewness in Ensemble Data Assimilation
Authors: Hodyss Daniel 
Published: February 2012

AbstractA practical data assimilation algorithm is presented that explicitly accounts for skewness in the prior distribution. The algorithm operates as a global solve (all observations are considered at once) using a minimization-based approach and Schur–Hadamard (elementwise) localization. The central feature of this technique is the squaring of the innovation and the ensemble perturbations so as to create an extended state space that accounts for the second, third, and fourth moments of the prior distribution. This new technique is illustrated in a simple scalar system as well as in a Boussinesq model configured to simulate nonlinearly evolving shear instabilities (Kelvin–Helmholtz waves). It is shown that an ensemble size of at least 100 members is needed to adequately resolve the third and fourth moments required for the algorithm. For ensembles of this size it is shown that this new technique is superior to a state-of-the-art ensemble Kalman filter in situations with significant skewness; otherwise, the new algorithm reduces to the performance of the ensemble Kalman filter.
Comparison of Subcutaneous and Intravenous Administration of Trastuzumab: A Phase I/Ib Trial in Healthy Male Volunteers and Patients With HER2‐Positive Breast Cancer
Authors: Wynne Chris , Harvey Vernon , Schwabe Christian , Waaka Devonie , McIntyre Christine , Bittner Beate 
Published: February 2012

AbstractTrastuzumab is a key component of treatment for human epidermal growth factor receptor 2 (HER2)–positive breast cancer in both the early and metastatic settings. It is administered intravenously, with between 17 and 52 infusions in standard regimens over 1 year. Intravenous administration of trastuzumab requires substantial time commitments for patients and health care professionals and can result in patient discomfort. A subcutaneous formulation of trastuzumab, containing recombinant human hyaluronidase to overcome subcutaneous absorption barriers, would reduce the administration duration and remove the need to establish intravenous access, thus improving the overall convenience of trastuzumab administration. This open‐label, 2‐part, phase I/Ib study (NCT00800436) was undertaken in healthy male volunteers and female patients with HER2‐positive early breast cancer to identify the dose of subcutaneous trastuzumab that resulted in exposure comparable with the approved intravenous trastuzumab dose. A subcutaneous trastuzumab dose of 8 mg/kg was found to result in exposure comparable with the intravenous trastuzumab dose of 6 mg/kg. The subcutaneous formulation was well tolerated, with a trend toward fewer adverse events versus intravenous administration; most adverse events were mild in intensity. These results support an ongoing phase III efficacy and safety study comparing a fixed subcutaneous trastuzumab dose with intravenous trastuzumab administration.
Exploring the role narrative free-text plays in discrepancies between physician coding and the InterVA regarding determination of malaria as cause of death, in a malaria holo-endemic region
Authors: Rankin Johanna C , Lorenz Eva , Neuhann Florian , Yé Maurice , Sié Ali , Becher Heiko , Ramroth Heribert 
Published: February 2012

Abstract

Background
In countries where tracking mortality and clinical cause of death are not routinely undertaken, gathering verbal autopsies (VA) is the principal method of estimating cause of death. The most common method for determining probable cause of death from the VA interview is Physician-Certified Verbal Autopsy (PCVA). A recent alternative method to interpret Verbal Autopsy (InterVA) is a computer model using a Bayesian approach to derive posterior probabilities for causes of death, given an a priori distribution at population level and a set of interview-based indicators. The model uses the same input information as PCVA, with the exception of narrative text information, which physicians can consult but which were not inputted into the model. Comparing the results of physician coding with the model, large differences could be due to difficulties in diagnosing malaria, especially in holo-endemic regions. Thus, the aim of the study was to explore whether physicians' access to electronically unavailable narrative text helps to explain the large discrepancy in malaria cause-specific mortality fractions (CSMFs) in physician coding versus the model.

Methods
Free-texts of electronically available records (N = 5,649) were summarised and incorporated into the InterVA version 3 (InterVA-3) for three sub-groups: (i) a 10%-representative subsample (N = 493) (ii) records diagnosed as malaria by physicians and not by the model (N = 1035), and (iii) records diagnosed by the model as malaria, but not by physicians (N = 332). CSMF results before and after free-text incorporation were compared.

Results
There were changes of between 5.5-10.2% between models before and after free-text incorporation. No impact on malaria CSMFs was seen in the representative sub-sample, but the proportion of malaria as cause of death increased in the physician sub-sample (2.7%) and saw a large decrease in the InterVA subsample (9.9%). Information on 13/106 indicators appeared at least once in the free-texts that had not been matched to any item in the structured, electronically available portion of the Nouna questionnaire.

Discussion
Free-texts are helpful in gathering information not adequately captured in VA questionnaires, though access to free-text does not explain differences in physician and model determination of malaria as cause of death.
Preparation, characterization, and application of titanium nano-tube array in dye-sensitized solar cells
Authors: Ho Shih-Yu , Su Chaochin , Cheng Chieh-Chung , Kathirvel Sasipriya , Li Chung-Yen , Li Wen-Ren 
Published: February 2012

Abstract
The vertically orientated TiO2 nanotube array (TNA) decorated with TiO2 nano-particles was successfully fabricated by electrochemically anodizing titanium (Ti) foils followed by Ti-precursor post-treatment and annealing process. The TNA morphology characterized by SEM and TEM was found to be filled with TiO2 nano-particles interior and exterior of the TiO2 nano-tubes after titanium (IV) n-butoxide (TnB) treatment, whereas TiO2 nano-particles were only found inside of TiO2 nano-tubes upon titanium tetrachloride (TiCl4) treatment. The efficiency in TNA-based DSSCs was improved by both TnB and TiCl4 treatment presumably due to the increase of dye adsorption.
Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models
Authors: Lee Young-Jung , Choi Dong-Young , Choi Im Seop , Kim Ki Ho , Kim Young Hee , Kim Hwan Mook , Lee Kiho , Cho Won Gil , Jung Jea Kyung , Han Sang Bae , Han Jin-Yi , Nam Sang-Yoon , Yun Young Won , Jeong Jae Hwang , Oh Ki-Wan , Hong Jin Tae 
Published: February 2012

Abstract

Background
Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms.

Methods
We investigated whether 4-O-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-O-methylhonkiol (0.5, 1 and 2 μM).

Results
Oral administration of 4-O-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-O-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4-O-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-O-methylhonokiol inhibited LPS-induced Aβ1-42 generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.

Conclusion
These results suggest that 4-O-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-O-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.
Segmental correction of adolescent idiopathic scoliosis by all-screw fixation method in adolescents and young adults. minimum 5 years follow-up with SF-36 questionnaire
Authors: Yu Ching-Hsiao , Chen Po-Quang , Ma Shu-Chuang , Pan Chee-Huan 
Published: February 2012

Abstract

Background
In our institution, the fixation technique in treating idiopathic scoliosis was shifted from hybrid fixation to the all-screw method beginning in 2000. We conducted this study to assess the intermediate -term outcome of all-screw method in treating adolescent idiopathic scoliosis (AIS).

Methods
Forty-nine consecutive patients were retrospectively included with minimum of 5-year follow-up (mean, 6.1; range, 5.1-7.3 years). The average age of surgery was 18.5 ± 5.0 years. We assessed radiographic measurements at preoperative (Preop), postoperative (PO) and final follow-up (FFU) period. Curve correction rate, correction loss rate, complications, accuracy of pedicle screws and SF-36 scores were analyzed.

Results
The average major curve was corrected from 58.0 ± 13.0° Preop to 16.0 ± 9.0° PO(p < 0.0001), and increased to 18.4 ± 8.6°(p = 0.12) FFU. This revealed a 72.7% correction rate and a correction loss of 2.4° (3.92%). The thoracic kyphosis decreased little at FFU (22 ± 12° to 20 ± 6°, (p = 0.25)). Apical vertebral rotation decreased from 2.1 ± 0.8 PreOP to 0.8 ± 0.8 at FFU (Nash-Moe grading, p < 0.01). Among total 831 pedicle screws, 56 (6.7%) were found to be malpositioned. Compared with 2069 age-matched Taiwanese, SF-36 scores showed inferior result in 2 variables: physical function and role physical.

Conclusion
Follow-up more than 5 years, the authors suggest that all-screw method is an efficient and safe method.
Ultrasound-guided foam sclerotherapy within a rolling treatment programme is an effective low-cost treatment for superficial venous insufficiency
Authors: Abbassi-Ghadi N , Hafez H 
Published: February 2012

Aims To review the results and cost of a rolling ultrasound-guided foam sclerotherapy (UGFS) treatment programme for patients with chronic superficial venous insufficiency. Method A prospective study of a rolling treatment programme where patients were offered unlimited follow-up at intervals of 6–8 weeks and further (top up) UGFS when necessary, until occlusion criteria were met. Results A total of 213 lower limbs with complete follow-up were included in the study. Median (range) age was 57 (16–94) years, maximum diameter of varicose vein was 10 (3–18) mm, C of CEAP (clinical, aetiological, anatomical and pathological elements) was 4 (2–6), number of treatment sessions was one (1–4) and follow-up was three (1.5–33) months. Satisfactory occlusion could not be achieved in nine (4%) limbs. The ratio of odds (95% CI) for requiring more than one treatment session was 3.58 (1.46–8.77), P = 0.002 for great saphenous varicosity and 2.11 (1.13–3.94), P = 0.015 for age 50 or more. There were 20 (9.3%) immediate and 63 (29.5%) delayed adverse effects. All were minor except for one cutaneous nerve injury, one pulmonary embolism and one infected haematoma. The ratio for odds (95% CI) for post-treatment skin discolouration was 2.59 (1.14–5.87), P = 0.017 for women and 1.32 (1.02–1.71), P = 0.032 for increasing sclerosant volume used. Service line costing per completed treatment episode was £115.22 (€130.07, $188.60). Conclusion UGFS in a rolling treatment programme is safe and can achieve high occlusion rates at a low cost. Patients above the age of 50 with great saphenous varicosity are likely to require more than one treatment session.
Polished Person or Parasite? The Implications of Education for Social Identities and Self Concepts and the Culturally Diverse Emotional Consequences. An Indian Example
Authors: Clemens Iris 
Published: February 2012

Abstract
Education is not only an innocent tool but leads to many conflicts all over the world as well. For an analysis of these conflicts one has to keep in mind that education as a concept is a culturally diverse construction with very different connotations in theory as much as in the everyday world. Taking the example of an empirical study on concepts of education and educated persons in an Indian urban middle class sample, the implications of cultural constructions of education for self concepts, social identities and therefore for social inclusion and exclusion will be discussed. Following the figure of Sanskritization by Srinivas, the founded pattern of argumentation in the data is called educationalization.