Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning the local molecular pattern of Alzheimer's disease by non-negative matrix factorization

Gene microarray technology is an effective tool to monitor simultaneous activity of multiple cellular pathways from thousands of genes in a single chip. Many clustering methods have been developed to identify groups of genes or experimental conditions that exhibit similar expression patterns from gene expression data, such as hierarchical clustering, k-means, and self-organizing maps (SOM). The limitations of these clustering algorithms are: they group genes (or conditions) based on global similarities in their expression profiles and only assign each gene to a single cluster. In this work we present a biclustering method-nonnegtive matrix factorization (NMF) to avoid the above drawbacks and discover the local molecular pattern from gene expression datasets of Alzheimer's disease (AD). NMF can be applied to reduce the dimensionality of the data and describe the data as a positive linear combination of a reduced number of factors. By applying a sparseness enforcement variable into classical NMF, the more local structures with meaningful biological information inherent in the data are captured by clustering genes and samples simultaneously, and the classification of samples is well improved. The analysis and discussion of the identified local structures demonstrated that they related many pathways which play a prominent role in AD and the activation patterns to AD phenotypes.
Membrane-associated cytochrome cy of Rhodobacter capsulatus is an electron carrier from the cytochrome bc1 complex to the cytochrome c oxidase during respiration

We have recently established that the facultative phototrophic bacterium Rhodobacter capsulatus has two different pathways for reduction of the photooxidized reaction center during photosynthesis (F.E. Jenney and F. Daldal, EMBO J. 12:1283-1292, 1993; F.E. Jenney, R.C. Prince, and F. Daldal, Biochemistry 33:2496-2502, 1994). One pathway is via the well-characterized, water-soluble cytochrome c2 (cyt c2), and the other is via a novel membrane-associated c-type cytochrome named cyt cy. In this work, we probed the role of cyt cy in respiratory electron transport by isolating a set of R. capsulatus mutants lacking either cyt c2 or cyt cy, in the presence or in the absence of a functional quinol oxidase-dependent alternate respiratory pathway. The growth and inhibitor sensitivity patterns of these mutants, their respiratory rates in the presence of specific inhibitors, and the oxidation-reduction kinetics of c-type cytochromes monitored under appropriate conditions demonstrated that cyt cy, like cyt c2, connects the bc1 complex and the cyt c oxidase during respiratory electron transport. Whether cyt c2 and cyt cy are the only electron carriers between these two energy-transducing membrane complexes of R. capsulatus is unknown.
The Fearful and Anxious Professional: Partner Experiences of Working in the Financialized Professional Services Firm

This article explores the work and career of law firm partners in the context of a financialized organizational regime, highlighting the effects of performance measures and metrics on the ways partners see themselves and their careers. The empirical analysis reveals a sense of fear and anxiety as partners experience the scrutiny and pressure of financialized performance management. Furthermore, it reveals partners face contradictory demands as they are pushed to meet financial and ‘citizen’ objectives within the firm. The result is a career as a ‘project of the self’ that relies on various protection strategies and which results in professionals captured by ‘financialization’ and unable to assimilate its demands in ways that protect traditional professional values.
Identification of a Novel Virulence Factor in Burkholderia cenocepacia H111 Required for Efficient Slow Killing of Caenorhabditis elegans

ABSTRACT Burkholderia cenocepacia H111, which was isolated from a cystic fibrosis patient, employs a quorum-sensing (QS) system, encoded by cep, to control the expression of virulence factors as well as the formation of biofilms. The QS system is thought to ensure that pathogenic traits are expressed only when the bacterial population density is high enough to overwhelm the host before it is able to mount an efficient response. While the wild-type strain effectively kills the nematode Caenorhabditis elegans, the pathogenicity of mutants with defective quorum sensing is attenuated. To date, very little is known about the cep-regulated virulence factors required for nematode killing. Here we report the identification of a cep-regulated gene, whose predicted amino acid sequence is highly similar to the QS-regulated protein AidA of the plant pathogen Ralstonia solanacearum. By use of polyclonal antibodies directed against AidA, it is demonstrated that the protein is expressed in the late-exponential phase and accumulates during growth arrest. We show that B. cenocepacia H111 AidA is essential for slow killing of C. elegans but has little effect on fast killing, suggesting that the protein plays a role in the accumulation of the strain in the nematode gut. Thus, AidA appears to be required for establishing an infection-like process rather than acting as a toxin. Furthermore, evidence is provided that AidA is produced not only by B. cenocepacia but also by many other strains of the Burkholderia cepacia complex.
Discrimination of DNA binding sites by mutant p53 proteins

Critical determinants of DNA recognition by p53 have been identified by a molecular genetic approach. The wild-type human p53 fragment containing amino acids 71 to 330 (p53(71-330)) was used for in vitro DNA binding assays, and full-length human p53 was used for transactivation assays with Saccharomyces cerevisiae. First, we defined the DNA binding specificity of the wild-type p53 fragment by using systematically altered forms of a known consensus DNA site. This refinement indicates that p53 binds with high affinity to two repeats of PuGPuCA.TGPyCPy, a further refinement of an earlier defined consensus half site PuPuPuC(A/T). (T/A) GPyPyPy. These results were further confirmed by transactivation assays of yeast by using full-length human p53 and systematically altered DNA sites. Dimers of the pentamer AGGCA oriented either head-to-head or tail-to-tail bound efficiently, but transactivation was facilitated only through head-to-head dimers. To determine the origins of specificity in DNA binding by p53, we identified mutations that lead to altered specificities of DNA binding. Single-amino-acid substitutions were made at several positions within the DNA binding domain of p53, and this set of p53 point mutants were tested with DNA site variants for DNA binding. DNA binding analyses showed that the mutants Lys-120 to Asn, Cys-277 to Gln or Arg, and Arg-283 to Gln bind to sites with noncanonical base pair changes at positions 2, 3, and 1 in the pentamer (PuGPuCA), respectively. Thus, we implicate these residues in amino acid-base pair contacts. Interestingly, mutant Cys-277 to Gln bound a consensus site as two and four monomers, as opposed to the wild-type p53 fragment, which invariably binds this site as four monomers.
Species Delimitation and Description of Mesocriconema nebraskense n. sp. (Nematoda: Criconematidae), a Morphologically Cryptic, Parthenogenetic Species from North American Grasslands

Abstract Nematode surveys of North American grasslands conducted from 2010 to 2015 frequently recovered a species of crico- nematid nematode morphologically resembling Mesocriconema curvatum. These specimens were recovered from remnant native prairies in the central tallgrass ecoregion of North America, and not from surrounding agroecosystems. Historical records indicate that M. curvatum is a cosmopolitan species feeding on a wide range of agronomic and native plants. DNA barcoding indicates North American grasslands contain at least 10 phylogenetically distinct lineages of Mesocriconema that resemble, but are not, M. curvatum. Analysis of the two most common lineages reveals two distinctly different population structures. The variation in population structure suggests unique evolutionary histories associated with their diversification. These two major lineages share a sympatric distribution and their slight morphological differences contrast with a high level of genetic separation. Based on their genetic divergence, fixed diagnostic nucleotides, population structure, species delimitation metrics, and a sympatric distribution, we believe that one of these distinct lineages warrants formal nomenclatural recognition. Herein, we provide formal recognition for Mesocriconema nebraskense n. sp. and discuss its relationship to other Mesocriconema lineages discovered in native North American grasslands.
A computational approach to inferring cellular protein‐binding affinities from quantitative fluorescence resonance energy transfer imaging

Fluorescence resonance energy transfer (FRET) microscopy can measure the spatial distribution of protein interactions inside live cells. Such experiments give rise to complex data sets with many images of single cells, motivating data reduction and abstraction. In particular, determination of the value of the equilibrium dissociation constant (Kd) will provide a quantitative measure of protein–protein interactions, which is essential to reconstructing cellular signaling networks. Here, we investigate the feasibility of using quantitative FRET imaging of live cells to estimate the local value of Kd for two interacting labeled molecules. An algorithm is developed to infer the values of Kd using the intensity of individual voxels of 3‐D FRET microscopy images. The performance of our algorithm is investigated using synthetic test data, both in the absence and in the presence of endogenous (unlabeled) proteins. The influence of optical blurring caused by the microscope (confocal or wide field) and detection noise on the accuracy of Kd inference is studied. We show that deconvolution of images followed by analysis of intensity data at local level can improve the estimate of Kd. Finally, the performance of this algorithm using cellular data on the interaction between yellow fluorescent protein‐Rac and cyan fluorescent protein‐PBD in mammalian cells is shown.
Polarized Localization of Epithelial CXCL11 in Chronic Obstructive Pulmonary Disease and Mechanisms of T Cell Egression1

The exit of lymphocytes from the interstitium of the lung, across the bronchial epithelium and into the airway lumen, is known as egression, or luminal clearance. Egression is important for immune surveillance and the resolution of inflammation, but the mechanisms involved are unknown. We show that egression of human T cells across the bronchial epithelium is a multistep process, driven in part by a polarized transepithelial gradient of CXCL11 that is up-regulated in patients with chronic obstructive airways disease. Previous studies have shown that T cells can migrate across a disrupted bronchial epithelium, but we provide evidence that egression does not require epithelial injury, and can take place across an intact epithelial barrier. After negotiating the extracellular matrix, the T cell adheres to the basal surface of the bronchial epithelial cell using α4 and leukocyte function associated-1 integrins before crossing the epithelium in an leukocyte function associated-1-dependent way. We demonstrate an egression-dependent decrease in transepithelial resistance across the epithelium without gross alteration in tight-junction proteins. The process of egression has been relatively overlooked when considering the control of leukocyte trafficking in the lung and other epithelial organs. This study highlights the role of the respiratory epithelium in the trafficking of T lymphocytes from the pulmonary interstitium and into the large airways, during the onset and resolution of pulmonary inflammation.
Dual effect of prostaglandins on isolated intraocular porcine ciliary arteries

Purpose: Prostaglandin analogues are used to reduce the intraocular pressure (IOP) in glaucoma, but also affect the tone of the arteries supplying the ciliary body. Previously, the effect of prostaglandins has been studied on the extraocular ciliary arteries, whereas the effect on intraocular ciliary arteries has not been studied in detail.
Age‐associated dysregulation of protein metabolism in the mammalian oocyte

Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA‐Seq on individual growing follicles from reproductively young and old mice to identify age‐dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism. We further validated our RNA‐Seq data by comparing nucleolar structure and function in oocytes from reproductively young and old mice, as this organelle is central for protein production. We examined key nucleolar markers, including upstream binding transcription factor (UBTF), an RNA polymerase I cofactor, and fibrillarin, an rRNA methyltransferase. In oocytes from mice of advanced reproductive age, UBTF was primarily expressed in giant fibrillar centers (GFCs), structures associated with high levels of rDNA transcription, and fibrillarin expression was increased ~2‐fold. At the ultrastructural level, oocyte nucleoli from reproductively old mice had correspondingly more prominent fibrillar centers and dense fibrillar centers relative to young controls and more ribosomes were found in the cytoplasm. Taken together, our findings are significant because the growing oocyte is one of the most translationally active cells in the body and must accumulate high‐quality maternally derived proteins to support subsequent embryo development. Thus, perturbations in protein metabolism are likely to have a profound impact on gamete health.
Equitable and Quality Education for All of Africa? The Challenges of Using ict in Education

Technological advances are increasing interest in the potential role of information and communication technologies ( ICT ) in enabling quality education outcomes in Africa. At present, however, the geographies of ICT use in Africa is poorly understood, and ICT education policy development has occurred in a relative empirical void. Relevant studies have largely been focused on wealthier African nations, largely neglecting poorer regions where education issues are most acute. This article works to address this lacuna. Drawing upon extensive fieldwork, it provides a detailed snapshot of ICT use in education in the northern Sierra Leonean district of Koinadugu. We subsequently argue that a lack of access to electricity, along with limited numbers of qualified teaching staff, presents fundamental barriers for realizing ICT use in classroom settings. Nevertheless, we also identify some promising trends with respect to the informal use of mobile Internet by teachers and students to augment learning in the classroom.
Peptide arrays for kinome analysis: New opportunities and remaining challenges

Phosphorylation is the predominant mechanism of post‐translational modification for regulation of protein function. With central roles in virtually every cellular process, and strong linkages with many diseases, there is a considerable interest in defining, and ultimately controlling, kinase activities. Investigations of human cellular phosphorylation events, which includes over 500 different kinases and tens of thousands of phosphorylation targets, represent a daunting challenge for proteomic researchers and cell biologists alike. As such, there is a priority to develop tools that enable the evaluation of cellular phosphorylation events in a high‐throughput, and biologically relevant, fashion. Towards this objective, two distinct, but functionally related, experimental approaches have emerged; phosphoproteome investigations, which focus on the sub‐population of proteins which undergo phosphorylation and kinome analysis, which considers the activities of the kinase enzymes mediating these phosphorylation events. Within kinome analysis, peptide arrays have demonstrated considerable potential as a cost‐effective, high‐throughput approach for defining phosphorylation‐mediated signal transduction activity. In particular, a number of recent advances in the application of peptide arrays for kinome analysis have enabled researchers to tackle increasingly complex biological problems in a wider range of species. In this review, recent advances in kinomic analysis utilizing peptides arrays including several of the biological questions studied by our group, as well as outstanding challenges still facing this technology, are discussed.
Survival after failure of first-line chemotherapy in advanced gastric cancer patients: differences between Japan and the rest of the world

In this review, we focus on post-progression survival after first-line chemotherapy of advanced gastric cancer, and particularly the differences between Japan and the rest of the world. We reviewed 15 recent phase III trials of which 4 were solely recruited from Japanese and 11 from rest of the world. The patient characteristics age, performance status, previous gastrectomy and the number of metastatic sites were similar in Japan and rest of the world. However, the diffuse histological type was more common in Japan. While overall survival was longer in Japan (10.5-14.1 vs. 7.9-12.2 months), progression-free survival tended to be shorter in Japan (3.6-6.0 vs. 3.1-7.4 months). Post-progression survival calculated as the difference between median overall survival and progression-free survival was clearly longer in Japan (6.9-8.6 vs. 2.4-6.2 months). The proportion of patients receiving second-line chemotherapy (%2nd-CX) was quite different in Japan and rest of the world (69-85% vs. 11-59%). Correlations between %2nd-CX and post-progression survival were strong (Spearman's rank correlation coefficient; ρ = 0.86, P < 0.001). Correlations between %2nd-CX and ratio of post-progression survival to total overall survival were also strong (ρ = 0.84, P < 0.001). Because a survival benefit of second-CX was documented in several phase III trials, it can be concluded that higher %2nd-CX partly contributed to extended post-progression survival. However, considering that second-CX increased survival only by ~1.5 months at median, other factors such as third-line chemotherapy may have some influences to prolonged post-progression survival.
Gender and equitable benefit-sharing mechanisms through Agricultural Innovation Platforms in Rwanda

ABSTRACT The low level of participation of women in the marketing and selling of crops in some patriarchal societies in the developing world has been documented. This article uses a case studies approach to document in detail two successful Agricultural Innovation Platforms (AIPs), out of nine studied, in order to understand what makes a successful AIP. The study shows that AIP activities in Rwanda are contributing to the achievement of gender mainstreaming through the equitable sharing of benefits supported by social, policy, and capacity factors. The article then provides evidence of how such policy or social factors are operationalized; how AIPs utilize policy; and how AIP processes integrate with local social norms and capital.
Time Series with Interdependent Level and Second Moment: Statistical Testing and Applications with Greek External Trade and Simulated Data

This work aims to fill an existing gap in the literature regarding the statistical testing for the existence and the identification of the character of time-varying second moment in its dependence on a non-constant mean level in time series. To this end a new statistical testing procedure is introduced with some considerable advantages over the existing ones. Amongst others it is argued that the existing statistical tests are insufficient and sometimes lead to biased results. Further the effect of the application of this methodology on some crucial elements of time series modelling such as outlier detection and seasonal adjustment is examined, through case studies conducted on a comparative basis using both the new methodology and an established one. The severe consequences of the improper treatment of the type of time-varying second moment dealt with in this work are evidenced and emphasized. The data set comprises time series on monthly external trade statistics for Greece. Overall, the resulting empirical evidence favours the new approach. Further supporting evidence is provided by the application of the new methodology to simulated data.
Teamwork and place-based curriculum and instruction in teaching English to speakers of other languages

The purpose of this project is to apply the theories , of the educational reformer, John Dewey, to the discipline of English as a Foreign Language (EFL). Dewey's 1 revelations on the importance of experiential learning provide the foundation of the place-based curriculum movement in regular education. This project puts forth a j framework to incorporate community investigation, outdoor i education, and project-based learning into an EFL curriculum that is taught in the area of Big Bear Lake, l California. This project also features a curriculum component consisting of team-building activities aimed at J increasing self-esteem and intercultural communicative i competence. Five key concepts serve in the development of the ! curriculum design: background and present theories of experiential education; the importance of place-based ! curriculum and instruction; team-building; intercultural , communicative competence, and second language acquisition theories. The above concepts, though different in nature, intersect to provide the basis for a curriculum plan that emphasizes direct experience and students' in-depth knowledge of place. In light of the need for intercultural
Small RNA in rice genome

Rice has many characteristics of a model plant. The recent completion of the draft of the rice genome represents an important advance in our knowledge of plant biology and also has an important contribution to the understanding of general genomic evolution. Besides the rice genome finishing map, the next urgent step for rice researchers is to annotate the genes and noncoding functional sequences. The recent work shows that noncoding RNAs (ncRNAs) play significant roles in biological systems. We have explored all the known small RNAs (a kind of ncRNA) within rice genome and other six species sequences, including Arabidopsis, maize, yeast, worm, mouse and pig. As a result we find 160 out of 552 small RNAs (sRNAs) in database have homologs in 108 rice scaffolds, and almost all of them (99.41%) locate in intron regions of rice by gene predication. 19 sRNAs only appear in rice. More importantly, we find two special LJ14 sRNAs: one is located in a set of sRNA ZMU14SNR9(s) which only appears in three plants, 86% sequences of them can be compared as the same sequence in rice, Arabidopsis and maize; the other conserved sRNA XLHS7CU14 has a segment which appears in almost all these species from plants to animals. All these results indicate that sRNA do not have evident borderline between plants and animals.
A novel hypothesis on the sensitivity of the fecal occult blood test

Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening.