2,064 research outputs found

    In Situ Structure Characterization in Slot-Die-Printed All-Polymer Solar Cells with Efficiency Over 9%

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    Herein, high-performance printed all-polymer solar cells (all-PSCs) based on a bulk-heterojunction (BHJ) blend film are demonstrated using PTzBI as the donor and N2200 as the acceptor. A slot-die process is used to prepare the BHJ blend, which is a cost-effective, high-throughput approach to achieve large-area photovoltaic devices. The real-time crystallization of polymers in the film drying process is investigated by in situ grazing incidence wide-angle X-ray scattering characterization. Printing is found to significantly improve the crystallinity of the polymer blend in comparison with spin coating. Moreover, printing with 1,8-diiodooctane as the solvent additive enhances the polymer aggregation and crystallization during solvent evaporation, eventually leading to multi-length-scale phase separation, with PTzBI-rich domains in-between the N2200 crystalline fibers. This unique morphology achieved by printing fabrication results in an impressively high power conversion efficiency of 9.10%, which is the highest efficiency reported for printed all-PSCs. These findings provide important guidelines for controlling film drying dynamics for processing all-PSCs

    On reducing inconsistency of pairwise comparison matrices below an acceptance threshold

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    A recent work of the authors on the analysis of pairwise comparison matrices that can be made consistent by the modification of a few elements is continued and extended. Inconsistency indices are defined for indicating the overall quality of a pairwise comparison matrix. It is expected that serious contradictions in the matrix imply high inconsistency and vice versa. However, in the 35-year history of the applications of pairwise comparison matrices, only one of the indices, namely CR proposed by Saaty, has been associated to a general level of acceptance, by the well known ten percent rule. In the paper, we consider a wide class of inconsistency indices, including CR, CM proposed by Koczkodaj and Duszak and CI by Pel\'aez and Lamata. Assume that a threshold of acceptable inconsistency is given (for CR it can be 0.1). The aim is to find the minimal number of matrix elements, the appropriate modification of which makes the matrix acceptable. On the other hand, given the maximal number of modifiable matrix elements, the aim is to find the minimal level of inconsistency that can be achieved. In both cases the solution is derived from a nonlinear mixed-integer optimization problem. Results are applicable in decision support systems that allow real time interaction with the decision maker in order to review pairwise comparison matrices.Comment: 20 page

    Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.

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    While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor-positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135)

    Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

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    <p>Abstract</p> <p>Background</p> <p>Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent.</p> <p>Discussion</p> <p>Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery.</p> <p>Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome.</p> <p>Summary</p> <p>Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.</p

    Changes in Global Gene Expression in Response to Chemical and Genetic Perturbation of Chromatin Structure

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    DNA methylation is important for controlling gene expression in all eukaryotes. Microarray analysis of mutant and chemically-treated Arabidopsis thaliana seedlings with reduced DNA methylation revealed an altered gene expression profile after treatment with the DNA methylation inhibitor 5-aza-2′ deoxycytidine (5-AC), which included the upregulation of expression of many transposable elements. DNA damage-response genes were also coordinately upregulated by 5-AC treatment. In the ddm1 mutant, more specific changes in gene expression were observed, in particular for genes predicted to encode transposable elements in centromeric and pericentromeric locations. These results confirm that DDM1 has a very specific role in maintaining transcriptional silence of transposable elements, while chemical inhibitors of DNA methylation can affect gene expression at a global level

    Spatio-temporal Models of Lymphangiogenesis in Wound Healing

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    Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

    Isocitrate Dehydrogenase of Helicobacter pylori Potentially Induces Humoral Immune Response in Subjects with Peptic Ulcer Disease and Gastritis

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    Background. H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD), an important house keeping protein of H. pylori. Methodology/Principal Findings. Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA) in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. Conclusions/Significance. ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1) and therefore, may not be a notable proinflammatory agent

    Observation of CR Anisotropy with ARGO-YBJ

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    The measurement of the anisotropies of cosmic ray arrival direction provides important informations on the propagation mechanisms and on the identification of their sources. In this paper we report the observation of anisotropy regions at different angular scales. In particular, the observation of a possible anisotropy on scales between \sim 10 ^{\circ} and \sim 30 ^{\circ} suggests the presence of unknown features of the magnetic fields the charged cosmic rays propagate through, as well as potential contributions of nearby sources to the total flux of cosmic rays. Evidence of new weaker few-degree excesses throughout the sky region 195195^{\circ}\leq R.A. 315\leq 315^{\circ} is reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich, German

    The Polycomb Repressive Complex 2 Is a Potential Target of SUMO Modifications

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    The Polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood.Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXbeta interacts and enhances the sumoylation of SUZ12 in vivo suggesting that PIASXbeta could function as an E3-ligase for SUZ12.Taken together, our data identify sumoylation as a novel post-translational modification of components of the PRC2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription
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