A model of defiance : Reimaging the comparative analysis of concealed discourse in text

This paper proposes that texts produced in diverse oral-traditional environments exhibit similarities in their disguise of subversion, particularly social or political resistance to the status quo. The disguise used in a particular text reflects the relationship between the text and its referents, or the cultural environment in which the text is produced and used. Cross-textual similarities reflect the similar processes used to disguise subversive ideas. This paper explores the following questions: 1) How might a particular text have been used to disguise resistance to the dominant hegemony? 2) What is the nature of that resistance as it is presented in the text? 3) What comparisons might we find among textual disguises of resistance from various literatures?Not

Quantifying biogenic bias in screening libraries.

In lead discovery, libraries of 10(6) molecules are screened for biological activity. Given the over 10(60) drug-like molecules thought possible, such screens might never succeed. The fact that they do, even occasionally, implies a biased selection of library molecules. We have developed a method to quantify the bias in screening libraries toward biogenic molecules. With this approach, we consider what is missing from screening libraries and how they can be optimized

Ligand Similarity Complements Sequence, Physical Interaction, and Co-Expression for Gene Function Prediction

The expansion of protein-ligand annotation databases has enabled large-scale networking of proteins by ligand similarity. These ligand-based protein networks, which implicitly predict the ability of neighboring proteins to bind related ligands, may complement biologically-oriented gene networks, which are used to predict functional or disease relevance. To quantify the degree to which such ligand-based protein associations might complement functional genomic associations, including sequence similarity, physical protein-protein interactions, co-expression, and disease gene annotations, we calculated a network based on the Similarity Ensemble Approach (SEA: sea.docking.org), where protein neighbors reflect the similarity of their ligands. We also measured the similarity with functional genomic networks over a common set of 1,131 genes, and found that the networks had only small overlaps, which were significant only due to the large scale of the data. Consistent with the view that the networks contain different information, combining them substantially improved Molecular Function prediction within GO (from AUROC~0.63-0.75 for the individual data modalities to AUROC~0.8 in the aggregate). We investigated the boost in guilt-by-association gene function prediction when the networks are combined and describe underlying properties that can be further exploited

Kriteria Visibilitas Hilal Rukyatul Hilal Indonesia (Rhi) (Konsep, Kriteria, dan Implementasi)

Telah dilaksanakan observasi hilal dan hilal tua selama periode Zulhijjah 1427–Zulhijjah 1430 H (Januari 2007–Desember 2009) oleh jejaring titik observasi Rukyatul Hilal Indonesia (RHI) yang merentang dari lintang 5° LU hingga 31° LS, dengan ataupun tanpa bantuan alat bantu optik. Observasi menghasilkan 174 data visibilitas yang terdiri dari 107 visibilitas positif dan 67 visibilitas negatif. Analisis korelasi linier Lag dengan Best Time Bulan menghasilkan definisi baru tentang hilal, yaitu Bulan pasca konjungsi yang memiliki Lag ≤ 24 menit hingga Lag ≤ 40 menit saat Matahari terbenam. Hubungan Best Time dan Lag memenuhi persamaan linear Yallop hanya untuk Lag ≤ 40 menit. Analisis korelasi aD dan DAz dengan metode least–square menghasilkan persamaan kriteria RHI aD ≥ 0,099 DAz2–1,490 DAz + 10,382 yang bentuknya hampir sama dengan kriteria LAPAN, namun sangat berbeda dibanding kriteria Fotheringham–Maunder maupun Bruin. Analisa komparatif menyimpulkan asumsi yang dipergunakan “kriteria” Imkanur Rukyat versi MABIMS dan konsep wujudul hilal tidak terbukti. Sebaliknya, terdapat kesesuaian antara hasil observasi dengan kriteria Odeh

Structure-Based Optimization of a Non-\u3b2-lactam Lead Results in Inhibitors That Do Not Up-Regulate \u3b2-Lactamase Expression in Cell Culture

Bacterial expression of \u3b2-lactamases is the most widespread resistance mechanism to \u3b2 -lactam antibiotics. There is a pressing need for novel, non-\u3b2-lactam inhibitors of these enzymes. Our lead, compound 1, is chemically dissimilar to \u3b2 -lactams and is a noncovalent, competitive inhibitor of the enzyme. However, at 26 \u3bcM its activity is modest (Figure 1). Using the X-ray structure of the AmpC/1 complex as a template, 14 analogues were designed and synthesized. Among these, compound 10, had a Ki of 1 \u3bcM, 26-fold better than the lead. The structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 \uc5, respectively. Compound 10 was active in cell culture, reversing resistance to the third generation cephalosporin ceftazidime in bacterial pathogens expressing AmpC. In contrast to \u3b2-lactam-based inhibitors compound 10 did not up-regulate \u3b2-lactamase expression in cell culture but simply inhibited the enzyme expressed by the resistant bacteria. Its escape from this resistance mechanism derives from its dissimilarity to \u3b2 -lactam antibiotics

The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate

The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels–Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG–GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.: Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/40684/2007, Science 2007 Programe, PTDC/SAU-BMA/114059/2009).Ontario Ministry of Research and Innovation (Ontario Neurotrauma FoundationCanadian Institute of Health Research (MSS)Stem Cell Network (MJC

Modulation of bone marrow mesenchymal stem cell secretome by ECM-like hydrogels

It has been demonstrated that bone marrow mesenchymal stem cell (BM-MSCs) transplantation has beneficial effects on several central nervous system (CNS) debilitating conditions. Growing evidence indicate that trophic factors secreted by these cells are the key mechanism by which they are acting. These cells are frequently used in combination with 3D artificial matrices, for instance hydrogels, in tissue engineering-based approaches. However, so far, no study has been reported on the influence of such matrices, namely the presence or absence of extracellular matrix motifs, on BM-MSCs secretome and its effects in neuronal cell populations. In this sense, we herein studied the impact of a hydrogel, gellan gum, on the behavior and secretome of BM-MSCs, both in its commercial available form (commonly used in tissue engineering) and in a fibronectin peptide-modified form. The results showed that in the presence of a peptide in the gellan gum hydrogel, BM-MSCs presented higher proliferation and metabolic activity than in the regular hydrogel. Moreover, the typical spindle shape morphology of BM-MSCs was only observed in the modified hydrogel. The effects of the secretome of BM-MSCs were also affected by the chemical nature of the extracellular matrix. BM-MSCs cultured in the modified hydrogel were able to secrete factors that induced higher metabolic viabilities and neuronal cell densities, when compared to those of the unmodified hydrogel. Thus adding a peptide sequence to the gellan gum had a significant effect on the morphology, activity, proliferation and secretome of BM-MSCs. These results highlight the importance of mimicking the extracellular matrix when BM-MSCs are cultured in hydrogels for CNS applications.We would like to acknowledge the funds attributed by the Portuguese Foundation for Science and Technology (FCT) (Grant No PTDC/SAU-BMA/114059/2009; pre-doctoral fellowships to N.A. Silva, SFRH/BD/40684/2007; Ciencia 2007 Program to A.J. Salgado; PEst-C/SAU/LA0001/2013-2014 and RNEM-REDE/1506/REM/2005). This work was partially funded by EU-FP7-Health-2011-Collaborative Project 278612, Biohybrid Templates for Peripheral Nerve Regeneration, and co-funded by Programa Operacional Regional do Norte (ON.2 - O Novo Norte), ao abrigo do Quadro de Referencia Estrategico Nacional (QREN), atraves do Fundo Europeu de Desenvolvimento Regional (FEDER)

Quantifying osmotic membrane fouling to enable comparisons across diverse processes

In this study, a method of in situ membrane fouling quantification is developed that enables comparisons of foulant accumulation between desalination processes with different membranes, driving forces, and feed solutions. Unlike the conventional metric of flux decline, which measures the response of a process to fouling, the proposed method quantifies the foulant accumulation. Foulant accumulation is parameterized by two variables, cake structural parameter and hydraulic diameter, that are calculated from flux measurements using a model for salt and water transport through fouled reverse osmosis (RO) and forward osmosis (FO) membranes, including dispersive mass transfer in the FO membrane support layer. Model results show that pressure declines through the foulant layer and can, in FO, reach negative absolute values at the membrane. Experimental alginate gel fouling rates are measured within a range of feed ionic compositions where cake hydraulic resistance is negligible. Using both flux decline and cake structural parameter as metrics, the effect of feed salinity on RO fouling is tested and RO is compared to FO. When RO is fouled with alginate, feed salinity and membrane permeability affect flux decline but not foulant accumulation rate. Between FO and RO, the initial rates of foulant accumulation are similar; however, FO exhibits slower flux decline, which causes greater foulant accumulation over time. The new methodology enables meaningful quantification and comparison of fouling rates with the aim of improving fundamental understanding of fouling processes.Center for Clean Water and Clean Energy at MIT and KFUPM (Project R4-CW-11)MIT Martin Family Society of Fellows for SustainabilityNational Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374