bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting cholesterol-rich microdomains to circumvent tamoxifen-resistant breast cancer
Authors: Tiwary Richa , Yu Weiping , deGraffenried Linda A , Sanders Bob G , Kline Kimberly 
Published: November 2011

Abstract
Introduction
Adjuvant treatment with tamoxifen substantially improves survival of women with estrogen-receptor positive (ER+) tumors. Tamoxifen resistance (TAMR) limits clinical benefit. RRR-α-tocopherol ether-linked acetic acid analogue (α-TEA) is a small bioactive lipid with potent anticancer activity. We evaluated the ability of α-TEA in the presence of tamoxifen to circumvent TAMR in human breast cancer cell lines.

Methods
Two genotypically matched sets of TAM-sensitive (TAMS) and TAM-resistant (TAMR) human breast cancer cell lines were assessed for signal-transduction events with Western blotting, apoptosis induction with Annexin V-FITC/PI assays, and characterization of cholesterol-rich microdomains with fluorescence staining. Critical involvement of selected mediators was determined by using RNA interference and chemical inhibitors.

Results
Growth-factor receptors (total and phosphorylated forms of HER-1 and HER-2), their downstream prosurvival mediators pAkt, pmTOR, and pERK1/2, phosphorylated form of estrogen receptor-α (pER-α at Ser-167 and Ser-118, and cholesterol-rich lipid microdomains were highly amplified in TAMR cell lines and enhanced by treatment with TAM. α-TEA disrupted cholesterol-rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators, and induced DR5-mediated mitochondria-dependent apoptosis via an endoplasmic reticulum stress-triggered pro-death pJNK/CHOP/DR5 amplification loop. Furthermore, methyl-β-cyclodextrin (MβCD), a chemical disruptor of cholesterol rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators and to induce apoptosis.

Conclusions
Data for the first time document that targeting cholesterol-rich lipid microdomains is a potential strategy to circumvent TAMR, and the combination of α-TEA + TAM can circumvent TAMR by suppression of prosurvival signaling via disruption of cholesterol-rich lipid microdomains and activation of apoptotic pathways via induction of endoplasmic reticulum stress.
Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial
Authors: Di Marco Fabiano , Centanni Stefano , Bellone Andrea , Messinesi Grazia , Pesci Alberto , Scala Raffaele , Perren Andreas , Nava Stefano 
Published: November 2011

Abstract
Introduction
The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven.

Methods
The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled.

Results
Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization.

Conclusions
The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged.

Trial registration
ClinicalTrials.gov NCT01291303.
Evolution of CT pulmonary angiography: referral patterns and diagnostic yield in 2009 compared with 2006
Authors: David Sarojini , Beddy Peter , Babar Judith , Devaraj Anand 
Published: November 2011

Background CT pulmonary angiography (CTPA) is an increasingly popular imaging test for assessing patients with acute chest pain. Purpose To evaluate the number of CTPA performed in 2009 compared with 2006 and assess the frequency of pulmonary embolus (PE) versus alternative diagnoses. Material and Methods Numbers of CTPA and V/Q scans performed in a six-month period of 2006 and 2009 were established by review of the hospital radiology information system. CTPAs were evaluated by two radiologists in consensus and the incidence of pulmonary embolism and alternative diagnoses in 2006 and 2009 were recorded. Results The final study groups were 99 patients who underwent CTPA in 2006 and 149 patients in 2009. There was a significant fall in the incidence of PE identified on CTPA in 2009 compared to 2006 (11% versus 21%, P = 0.04). There was a non-significant rise in the incidence of alternative diagnoses in 2009 compared to 2006 (45% versus 40%, P = 0.48). Nine types of alternative radiological diagnoses were made on CTPA, the most common of which was pneumonia in both time periods (17% and 12%). Eighty-seven V/Q scans were performed in the study period in 2006, compared to 109 in 2009. The incidence of PE identified on V/Q scanning remained stable (8% in 2009 versus 12% in 2006, P = 0.44). Conclusion The numbers of CTPAs being performed has increased in three years. The incidence of PE identified has fallen and there has been a modest increase in the number of alternative diagnoses.
Iberian intertidal turf assemblages dominated byErythroglossum lusitanicum(Ceramiales, Rhodophyta): structure, temporal dynamics, and phenology
Authors: Tapia Pilar Díaz , Bárbara Ignacio , Barreiro Rodolfo 
Published: November 2011

AbstractErythroglossum lusitanicumis a foliose, turf-forming member of the Delesseriaceae that colonizes sand-covered intertidal rocks on the Atlantic Iberian Peninsula. We examined (i) the phenology of this alga and (ii) the structure and temporal dynamics of its associated flora at two sites over one year. Species diversity was low in the assemblage, which was dominated byE. lusitanicum.Assemblage structure was essentially constant through the year. There were, however, significant differences inE. lusitanicumcharacteristics between the two sites. At one,E. lusitanicumwas more abundant, thalli were longer and wider, and the proportion of plants with tetrasporangia was higher than at the second location. At the first site, the phenological traits tracked a temporal cycle. Thallus length and blade width were highest in April; after gradual deterioration of the apical portions of the plants, individual sizes reached minimum values in July. Subsequently, individual growth rate was low and plant length was nearly constant from September to February. Tetrasporangia were common throughout most of the year; only in July they were totally absent. Temperature and daylength were inversely related to reproduction. Sexual reproductive structures were not observed. The abundant growth of basal proliferations suggests that vegetative propagation very probably plays an important role in the maintenance ofE. lusitanicumpopulations.
The Progressivity of Social Security
Authors: Coronado Julia Lynn , Fullerton Don , Glass Thomas 
Published: November 2011

Abstract
How much does the current social security system redistribute from rich to poor? We propose alternative concepts of well-being that can be used to classify individuals from rich to poor, and we show how social security redistributes differently under each concept. We use the PSID to estimate lifetime wage profiles and actual earnings each year for a sample of 1778 individuals, and we use mortality probabilities to calculate expected payroll taxes and social security benefits. For a given set of “facts” about the net flows experienced each year by each individual, measured progressivity depends on many assumptions. This paper attempts to capture and to quantify all of the data and characteristics relevant to determine each individual’s “income” under several definitions. We then use each definition of income to classify individuals from rich to poor and to calculate the progressivity of social security.
We proceed in seven steps. First, we classify individuals by annual income and use Gini coefficients to find that social security is highly progressive. Second, we reclassify individuals on the basis of lifetime income and find that social security is less progressive. Third, we remove the cap on measured earnings and find that social security is even less progressive. Fourth, we switch from actual to potential lifetime earnings (the present value of the wage rate times 4000 hours each year). This measure captures the value of leisure and home production, so those out of the labor force are less poor, and net payments to them are less progressive. Fifth, we assign to each married individual half of the couple’s income. The low-wage spouse is then not so poor, and social security becomes even less progressive. Sixth, we incorporate mortality probabilities that differ by potential lifetime income. Since the rich live longer and collect benefits longer, social security is no longer progressive. Finally, we increase the discount rate from 2% to 4%, which puts relatively more weight on the earlier-but-regressive payroll tax and less weight on the later-but-progressive benefit schedule.
Depending on the definition of income used to classify people, the overall social security system could be deemed progressive, only mildly progressive, or neutral. With an even-higher discount rate, it could even be deemed regressive.
What Are the Police Doing on Twitter? Social Media, the Police and the Public
Authors: Crump Jeremy 
Published: November 2011

AbstractThis article examines the growing interest since 2008 of UK police forces in the use of social media as a basis for engagement with the public. This interest is set in the context of a political agenda for increasing public trust and confidence in the police and enlistment of the public as jointly responsible for crime reduction. An ambitious national police agenda led by the Association of Chief Police Officers has promoted the use of social media to engage groups previously uninvolved in discussion of local policing, and has envisaged its use as a basis for deliberation about priorities. This article investigates how successful this endeavour has been, and how far a hierarchical organisation ‐ the police service ‐ has been able to exploit the networked characteristics of social media and the potential of user created content. The paper analyses the police use of one particular platform, Twitter, including the structure of networks and the content of the messages. The article concludes that the constraints of police culture have meant that Twitter has been used cautiously and as a reinforcement for existing means of communication. It puts forward key issues which need to be addressed if the more ambitious aims for social media are to be achieved.
Sensitivity to Change and Responsiveness of Four Balance Measures for Community-Dwelling Older Adults
Authors: Pardasaney Poonam K. , Latham Nancy K. , Jette Alan M. , Wagenaar Robert C. , Ni Pengsheng , Slavin Mary D. , Bean Jonathan F. 
Published: November 2011

BackgroundImpaired balance has a significant negative impact on mobility, functional independence, and fall risk in older adults. Although several, well-respected balance measures are currently in use, there is limited evidence regarding the most appropriate measure to assess change in community-dwelling older adults.ObjectiveThe aim of this study was to compare floor and ceiling effects, sensitivity to change, and responsiveness across the following balance measures in community-dwelling elderly people with functional limitations: Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment total scale (POMA-T), POMA balance subscale (POMA-B), and Dynamic Gait Index (DGI).DesignRetrospective data from a 16-week exercise trial were used. Secondary analyses were conducted on the total sample and by subgroups of baseline functional limitation or baseline balance scores.MethodsParticipants were 111 community-dwelling older adults 65 years of age or older, with functional limitations. Sensitivity to change was assessed using effect size, standardized response mean, and paired t tests. Responsiveness was assessed using minimally important difference (MID) estimates.ResultsNo floor effects were noted. Ceiling effects were observed on all measures, including in people with moderate to severe functional limitations. The POMA-T, POMA-B, and DGI showed significantly larger ceiling effects compared with the BBS. All measures had low sensitivity to change in total sample analyses. Subgroup analyses revealed significantly better sensitivity to change in people with lower compared with higher baseline balance scores. Although both the total sample and lower baseline balance subgroups showed statistically significant improvement from baseline to 16 weeks on all measures, only the lower balance subgroup showed change scores that consistently exceeded corresponding MID estimates.LimitationsThis study was limited to comparing 4 measures of balance, and anchor-based methods for assessing MID could not be reported.ConclusionsImportant limitations, including ceiling effects and relatively low sensitivity to change and responsiveness, were noted across all balance measures, highlighting their limited utility across the full spectrum of the community-dwelling elderly population. New, more challenging measures are needed for better discrimination of balance ability in community-dwelling elderly people at higher functional levels.
Une approche de la complementation verbale guidee par les corpus
Authors: Fabre Cécile , Rebeyrolle Josette 
Published: November 2011

Résumé Nous adoptons une approche principalement corpus-driven pour réexaminer la question de la complémentation verbale indirecte en proposant de substituer aux tests linguistiques de grammaticalité permettant de déterminer la fonction des syntagmes prépositionnels arguments ou circonstants) des mesures statistiques visant à apprécier, dans l’espace d’un corpus, le degré d’autonomie de ces syntagmes vis-à-vis du verbe. Nous montrons notamment comment de tels calculs permettent de guider la description linguistique en faisant émerger des types de fonctionnement particuliers, comme par exemple, des situations intermédiaires entre arguments et circonstants. La masse d’informations qui se trouve synthétisée à partir de deux corpus permet également de dégager des tendances générales et des usages différenciés d’un corpus à l’autre.
A Molecular Mechanism for TNF-α–Mediated Downregulation of B Cell Responses
Authors: Frasca Daniela , Romero Maria , Diaz Alain , Alter-Wolf Sarah , Ratliff Michelle , Landin Ana Marie , Riley Richard L. , Blomberg Bonnie B. 
Published: November 2011

Abstract
B cell function with age is decreased in class switch recombination (CSR), activation-induced cytidine deaminase (AID), and stability of E47 mRNA. The latter is regulated, at least in part, by tristetraprolin (TTP), which is increased in aged B cells and also negatively regulates TNF-α. In this study, we investigated whether B cells produce TNF-α, whether this changes with age, and how this affects their function upon stimulation. Our hypothesis is that in aging there is a feedback mechanism of autocrine inflammatory cytokines (TNF-α) that lowers the expression of AID and CSR. Our results showed that unstimulated B cells from old BALB/c mice make significantly more TNF-α mRNA and protein than do B cells from young mice, but after stimulation the old make less than the young; thus, they are refractory to stimulation. The increase in TNF-α made by old B cells is primarily due to follicular, but not minor, subsets of B cells. Incubation of B cells with TNF-α before LPS stimulation decreased both young and old B cell responses. Importantly, B cell function was restored by adding anti–TNF-α Ab to cultured B cells. To address a molecular mechanism, we found that incubation of B cells with TNF-α before LPS stimulation induced TTP, a physiological regulator of mRNA stability of the transcription factor E47, which is crucial for CSR. Finally, anti–TNF-α given in vivo increased B cell function in old, but not in young, follicular B cells. These results suggest new molecular mechanisms that contribute to reduced Ab responses in aging.
IL-17 Silencing Does Not Protect Nonobese Diabetic Mice from Autoimmune Diabetes
Authors: Joseph Julie , Bittner Stefan , Kaiser Fabian M. P. , Wiendl Heinz , Kissler Stephan 
Published: November 2011

Abstract
The long-held view that many autoimmune disorders are primarily driven by a Th1 response has been challenged by the discovery of Th17 cells. Since the identification of this distinct T cell subset, Th17 cells have been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Type 1 diabetes has also long been considered a Th1-dependent disease. In light of the emerging role for Th17 cells in autoimmunity, several recent studies investigated the potential of this subset to initiate autoimmune diabetes. However, direct evidence supporting the involvement of Th17 cells in actual pathogenesis, particularly during spontaneous onset, is lacking. In this study, we sought to directly address the role of IL-17, the cytokine by which Th17 cells are primarily characterized, in the pathogenesis of autoimmune diabetes. We used lentiviral transgenesis to generate NOD mice in which IL-17 is silenced by RNA interference. The loss of IL-17 had no effect on the frequency of spontaneous or cyclophosphamide-induced diabetes. In contrast, IL-17 silencing in transgenic NOD mice was sufficient to reduce the severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, consistent with reports that IL-17 deficiency is protective in this experimental model of multiple sclerosis. We concluded that IL-17 is dispensable, at least in large part, in the pathogenesis of autoimmune diabetes.
Distinct Regulation of Murine Lupus Susceptibility Genes by the IRF5/Blimp-1 Axis
Authors: Panchanathan Ravichandran , Liu Hongzhu , Liu Hongqi , Fang Chee-Mun , Erickson Loren D. , Pitha Paula M. , Choubey Divaker 
Published: November 2011

Abstract
Genome-wide association studies have identified lupus susceptibility genes such as IRF5 and PRDM1 (encoding for IFN regulatory factor 5 [IRF]5 and Blimp-1) in the human genome. Accordingly, the murine Irf5 and Prdm1 genes have been shown to play a role in lupus susceptibility. However, it remains unclear how IRF5 and Blimp-1 (a transcriptional target of IRF5) contribute to lupus susceptibility. Given that the murine lupus susceptibility locus Nba2 includes the IFN-regulated genes Ifi202 (encoding for the p202 protein), Aim2 (encoding for the Aim2 protein), and Fcgr2b (encoding for the FcγRIIB receptor), we investigated whether the IRF5/Blimp-1 axis could regulate the expression of these genes. We found that an Irf5 deficiency in mice decreased the expression of Blimp-1 and reduced the expression of the Ifi202. However, the deficiency increased the expression of Aim2 and Fcgr2b. Correspondingly, increased expression of IRF5 in cells increased levels of Blimp-1 and p202 protein. Moreover, Blimp-1 expression increased the expression of Ifi202, whereas it reduced the expression of Aim2. Interestingly, an Aim2 deficiency in female mice increased the expression of IRF5. Similarly, the Fcgr2b-deficient mice expressed increased levels of IRF5. Moreover, increased expression of IRF5 and Blimp-1 in lupus-prone C57BL/6.Nba2, New Zealand Black, and C57BL/6.Sle123 female mice (as compared with age-matched C57BL/6 female mice) was associated with increased levels of the p202 protein. Taken together, our observations demonstrate that the IRF5/Blimp-1 axis differentially regulates the expression of Nba2 lupus susceptibility genes, and they suggest an important role for the IRF5/Blimp-1/p202 axis in murine lupus susceptibility.
Arthroscopic Repair of Delaminated Acetabular Articular Cartilage Using Fibrin Adhesive. Results at One to Three Years
Authors: Stafford Giles H. , Bunn Jonathan R. , Villar Richard N. 
Published: November 2011

We describe one- to three-year results of a novel use of fibrin glue in the treatment of cartilage damage by arthroscopy in the hip. This technique uses the microfracture technique and fibrin adhesive to bond delaminated articular cartilage to the underlying subchondral bone. This is generally performed in conjunction with treatment of underlying pathology such as femoroacetabular impingement. Patients were assessed using the modified Harris Hip Score (MHHS) pre- and post-operatively, and statistical significance determined by Student's t-test. We report the mid-term results of 43 patients with femoroacetabular impingement who have undergone this technique for re-attachment of delaminated chondral flaps. There was a statistically significant improvement in MHHS at a mean of 28 months (16 to 42 months) after surgery (p<0.0001). The MHHS for pain improved significantly from 21.8 (95% CI 19.0 to 24.7) pre-operatively to 35.8 (95% CI 32.6 to 38.9) post-operatively (p<0.0001). The MHHS for function also showed significant, although more modest, improvements from 40.0 (95% CI 37.7 to 42.3) pre-operatively to 43.6 (95% CI 41.4 to 45.8) post-operatively (p=0.0006). There were three patients who had early (within 12 months of the index procedure) revision arthroscopy for iliopsoas pathology. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive is a useful technique in the treatment of early cartilage damage. We have seen encouraging mid-term results, although further studies are warranted.
Partial characterization of a novel amphibian hemoglobin as a model for graduate student investigation on peptide chemistry, mass spectrometry, and atomic force microscopy
Authors: Bemquerer Marcelo P. , Macedo Jéssica K. A. , Ribeiro Ana Carolina J. , Carvalho Andréa C. , Silva Débora O. C. , Braz Juliana M. , Medeiros Kelliane A. , Sallet Lunalva A. P. , Campos Pollyanna F. , Prates Maura V. , Silva Luciano P. 
Published: November 2011

AbstractGraduate students in chemistry, and in biological and biomedical fields must learn the fundamentals and practices of peptide and protein chemistry as early as possible. A project‐oriented approach was conducted by first‐year M.Sc and Ph.D students in biological sciences. A blind glass slide containing a cellular smear and an aqueous cellular extract were offered to the students. Qualitative and quantitative cell morphological parameters were analyzed by atomic force microscopy. The fractionation of the aqueous extract was conducted by reversed‐phase chromatography followed by analysis of the isolated and partially purified proteins and peptides by mass spectrometry (MS). The proteins were treated by peptidases and the obtained peptide fragments were sequenced by de novo MS/MS, together with peptides already present in the extract. The most abundant protein fractions were identified as the alpha and beta chains of hemoglobin from an amphibian of the Leptodactylus genera. Two of the peptides sequenced by the students were synthesized by the solid‐phase methodology, one of those being obtained by the split‐and‐pool library synthesis method. Thus, the students were able to learn some advanced principles and practices of protein chemistry and bionanotechnology in a 6‐weeks project‐oriented approach.