Miracle-dz/UniFAR-FTUs huggingface dataset:
Dectin-1 Interaction with Mycobacterium tuberculosis Leads to Enhanced IL-12p40 Production by Splenic Dendritic Cells1

Dectin-1 is a fungal pattern recognition receptor that binds to β-glucans and triggers cytokine production by facilitating interaction with TLR2 or by directly activating spleen tyrosine kinase (Syk). To assess the possible role of Dectin-1 in the innate response to mycobacteria, we used an in vitro system in which IL-12p40 production is measured in splenic dendritic cells (SpDC) following exposure to live Mycobacterium tuberculosis bacilli. Treatment of SpDC with laminarin or glucan phosphate, two molecules known to block Dectin-1-dependent activity, led to a reduction in M. tuberculosis-induced IL-12p40 as well as IL-12p70 production. Moreover, SpDC from Dectin-1−/− chimeric mice displayed reduced IL-12p40 production in response to mycobacteria when compared with Dectin-sufficient DC. Laminarin treatment also inhibited mycobacterial-induced IL-12p40 production in DC from TLR2−/− mice, arguing that Dectin-1 functions independently of TLR2 signaling in this system. Importantly, a Dectin-1 fusion protein was found to directly bind to live mycobacteria in a laminarin-inhibitable manner indicating the presence of ligands for the receptor in the bacterium and laminarin pretreatment resulted in reduced association of mycobacteria to SpDC. In additional experiments, mycobacterial stimulation was shown to be associated with increased phosphorylation of Syk and this response was inhibited by laminarin. Furthermore, pharmacologic inhibition of Syk reduced the M. tuberculosis-induced IL-12p40 response. Together, these findings support a role for Dectin-1 in promoting M. tuberculosis-induced IL-12p40 production by DC in which the receptor augments bacterial-host cell interaction and enhances the subsequent cytokine response through an unknown mechanism involving Syk signaling.
Vocational Education Course Taking and Post–High School Employment of Youth With Emotional Disturbances

Data from the National Longitudinal Transition Study–2 (NLTS2) were used to examine the patterns of career and technical education (CTE) course taking in high school by students receiving special education services for emotional disturbances (ED). Descriptive analyses indicate the extent of such course taking by students with ED and their engagement in a concentrated program of occupationally specific general education CTE, a level of CTE course taking that early research has linked to improved post–high school employment outcomes. Propensity scoring methods were used to determine the extent to which either type of CTE course taking was related to higher odds of full-time employment after high school and whether results differed with the length of time post high school. There was a significant positive effect for participating in a concentration of occupationally specific CTE in the first 2 post–high school years, but effects were non-significant for later years. Results showed no benefits of CTE course taking overall. The implications for high school programming and transition planning are discussed.
Scale-space measures for graph topology link protein network architecture to function

Motivation: The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). Results: In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions—genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture. Availability and implementation: MatlabTM code to calculate the scale-aware topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA Contact: j.deridder@tudelft.nl Supplementary information: Supplementary data are available at Bioinformatics online.
Alternative Splicing and Extensive RNA Editing of Human TPH2 Transcripts

Brain serotonin (5-HT) neurotransmission plays a key role in the regulation of mood and has been implicated in a variety of neuropsychiatric conditions. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT. Recently, we discovered a second TPH isoform (TPH2) in vertebrates, including man, which is predominantly expressed in brain, while the previously known TPH isoform (TPH1) is primarly a non-neuronal enzyme. Overwhelming evidence now points to TPH2 as a candidate gene for 5-HT-related psychiatric disorders. To assess the role of TPH2 gene variability in the etiology of psychiatric diseases we performed cDNA sequence analysis of TPH2 transcripts from human post mortem amygdala samples obtained from individuals with psychiatric disorders (drug abuse, schizophrenia, suicide) and controls. Here we show that TPH2 exists in two alternatively spliced variants in the coding region, denoted TPH2a and TPH2b. Moreover, we found evidence that the pre-mRNAs of both splice variants are dynamically RNA-edited in a mutually exclusive manner. Kinetic studies with cell lines expressing recombinant TPH2 variants revealed a higher activity of the novel TPH2B protein compared with the previously known TPH2A, whereas RNA editing was shown to inhibit the enzymatic activity of both TPH2 splice variants. Therefore, our results strongly suggest a complex fine-tuning of central nervous system 5-HT biosynthesis by TPH2 alternative splicing and RNA editing. Finally, we present molecular and large-scale linkage data evidencing that deregulated alternative splicing and RNA editing is involved in the etiology of psychiatric diseases, such as suicidal behaviour.
Category Stretching: Reorienting Research on Categories in Strategy, Entrepreneurship, and Organization Theory: Reorienting Research on Categories

We advocate for more tolerance in the manner we collectively address categories and categorization in our research. Drawing on the prototype view, organizational scholars have provided a ‘disciplining’ framework to explain how category membership shapes, impacts, and limits organizational success. By stretching the existing straightjacket of scholarship on categories, we point to other useful conceptualizations of categories – i.e. the causal-model and the goal-based approaches of categorization – and propose that depending on situational circumstances, and beyond a disciplining exercise, categories involve a cognitive test of congruence and a goal satisfying calculus. Unsettling the current consensus about categorical imperatives and market discipline, we suggest also that audiences may tolerate more often than previously thought organizations that blend, span, and stretch categories. We derive implications for research about multi-category membership and mediation in markets, and suggest ways in which work on the theme of categories in the strategy, entrepreneurship, and managerial cognition literatures can be enriched.
Flexibility of metal binding sites in proteins on a database scale

Protein metal binding sites in the pre‐bound (apo) state, and their rearrangements upon metal binding were not analyzed previously at a database scale. Such a study may provide valuable information for metal binding site prediction and design. A high resolution, nonredundant dataset of 210 metal binding sites was created, containing all available representatives of apo–holo pairs for the most populated metals in the PDB. More than 40% of the sites underwent rearrangements upon metal binding. In 30 cases rearrangements involved the backbone. The tendency for side‐chain rearrangement inversely correlates with the number of first‐shell residues. Analysis of side‐chain reorientations as a result of metal binding showed that in 95% of the rigid‐backbone binding sites at most one side chain moved. Thus, in general, part of the first coordination shell is already in place in the pre‐bound form. The frequencies of side‐chain reorientation directly correlated with metal ligand flexibility and solvent accessibility in the apo state. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Over-expression of Grhl2 causes spina bifida in the Axial defects mutant mouse

Cranial neural tube defects (NTDs) occur in mice carrying mutant alleles of many different genes, whereas isolated spinal NTDs (spina bifida) occur in fewer models, despite being common human birth defects. Spina bifida occurs at high frequency in the Axial defects (Axd) mouse mutant but the causative gene is not known. In the current study, the Axd mutation was mapped by linkage analysis. Within the critical genomic region, sequencing did not reveal a coding mutation whereas expression analysis demonstrated significant up-regulation of grainyhead-like 2 (Grhl2) in Axd mutant embryos. Expression of other candidate genes did not differ between genotypes. In order to test the hypothesis that over-expression of Grhl2 causes Axd NTDs, we performed a genetic cross to reduce Grhl2 function in Axd heterozygotes. Grhl2 loss of function mutant mice were generated and displayed both cranial and spinal NTDs. Compound heterozygotes carrying both loss (Grhl2 null) and putative gain of function (Axd) alleles exhibited normalization of spinal neural tube closure compared with Axd/+ littermates, which exhibit delayed closure. Grhl2 is expressed in the surface ectoderm and hindgut endoderm in the spinal region, overlapping with grainyhead-like 3 (Grhl3). Axd mutants display delayed eyelid closure, as reported in Grhl3 null embryos. Moreover, Axd mutant embryos exhibited increased ventral curvature of the spinal region and reduced proliferation in the hindgut, reminiscent of curly tail embryos, which carry a hypomorphic allele of Grhl3. Overall, our data suggest that defects in Axd mutant embryos result from over-expression of Grhl2.
Socialization experiences of Russian employees at the University of Alaska Fairbanks: cultural approach

This qualitative exploratory study examines Russian employees’ lived experiences at the University of Alaska Fairbanks (UAF) and the influence UAF culture has on the communicative socialization process. Like other international workers employed at various positions in American universities, Russian employees, especially Research and Teaching assistants, may experience difficulty in terms of language, culture, training, in terms of adapting to American culture, specifically American academic culture, to succeed in their jobs. The literature review for this study includes theoretical perspectives from intercultural communication, organizational communication, and the social construction of reality. Russian employees participate in in-depth narrative interviews about their communication experiences of socialization at UAF. Four repetitive themes emerge: (1) vulnerable self; (2) competition; (3) freedom; and (4) informality. Analysis also provides insight on cultural similarities and differences between Russians and Americans in their interactions at UAF, and on an interpersonal level. Implications for future research in relation to how cultural similarities and differences are revealed in a communication process between Russian graduate and professional students and their American counterparts, and how these similarities and differences affect their everyday interactions. Page SIGNATURE PAGE i TITLE PAGE „ ABSTRACT jjj TABLE OF CONTENTS . iv LIST OF APENDICES . v ACKNOWLEDGMENTS . v
Content-Based Clustered P2P Search Model Depending on Set Distance

The main issues that affect query efficiency and search cost in content-based unstructured P2P search system are the complexity of computing the similarity of the documents brought by high dimensions and the great deal of redundant messages coming with flooding. This paper defines the documents similarity by the way of set distance. This method restrains the complexity of computing the document similarity in linear time. Also, this paper clusters the peers based on content by their set distance to reduce the query time and redundant messages. Simulations show that the content-based search model constructed by set distance not only has higher recall, but also reduce the search cost and query time to the rate of 40% and 30% of Gnutella
Tissue classification with gene expression profiles

Constantly improving gene expression profiling technologies are expected to provide understanding and insight into cancer related cellular processes. Gene expression data is also expected to significantly and in the development of efficient cancer diagnosis and classification platforms. In this work we examine two sets of gene expression data measured across sets of tumor and normal clinical samples One set consists of 2,000 genes, measured in 62 epithelial colon samples [1]. The second consists of ≈ 100,000 clones, measured in 32 ovarian samples (unpublished, extension of data set described in [26]). We examine the use of scoring methods, measuring separation of tumors from normals using individual gene expression levels. These are then coupled with high dimensional classification methods to assess the classification power of complete expression profiles. We present results of performing leave-one-out cross validation (LOOCV) experiments on the two data sets. employing SVM [8], AdaBoost [13] and a novel clustering based classification technique. As tumor samples can differ from normal samples in their cell-type composition we also perform LOOCV experiments using appropriately modified sets of genes, attempting to eliminate the resulting bias. We demonstrate success rate of at least 90% in tumor vs normal classification, using sets of selected genes, with as well as without cellular contamination related members. These results are insensitive to the exact selection mechanism, over a certain range.
Some Ideas on How Political Scientists Can Develop Real World Implications From Their Research (Without Becoming Policy Wonks or Law Professors)

These quotes tell it like it is. A law review article without a prescriptive component is an oxymoron; a social science paper with a normative conclusion is just moronic. How we got to this sorry state is not just a mystery to us; it is the height of irony. Implications for the real world—whether normative, policy, design, or otherwise—should carry more weight when we derive them through a process that uses models and data. That is because statistical inference enables us (and our readers) to gauge the uncertainty (or, if you prefer, the reliability) of our conclusions with some degree of precision. In most other kinds of research, including many articles in the law reviews, scholars base their prescriptions on little more than speculation, intuition, and sheer guesswork. The question is how we can convince (quantitative) political scientists interested in law and legal institutions to be more attentive to the real world. The answer, we believe, does not lie in asking them to reorient their questions to address current policy concerns; most will not do it. The real career payoffs in political science
Heart surface motion estimation framework for robotic surgery employing meshless methods

A novel heart surface motion estimation framework for a robotic surgery on a stabilized beating heart is proposed. It includes an approach for the reconstruction and prediction of heart surface motion based on a novel physical model of the intervention area described by a distributed-parameter system. Instead of conventional element methods, a meshless method is used for a spatial and temporal decomposition of this system. This leads to a finite-dimensional state-space form. Furthermore, the state of the resulting lumped-parameter system, which provides an approximation of the deflection and velocity of the heart surface, is dynamically estimated under consideration of uncertainties both occurring in the system and arising from noisy camera measurements. By using the estimation results, an accurate reconstruction of heart surface motion for the synchronisation of the surgical instruments is also achieved at occluded or non-measurement points.
Di-retinoid-pyridinium-ethanolamine (A2E) Accumulation and the Maintenance of the Visual Cycle Are Independent of Atg7-mediated Autophagy in the Retinal Pigmented Epithelium*

Background: Atg7 is an essential autophagic enzyme. Disrupted autophagy has been implicated in retinal degeneration. Results: Mice with RPE-specific Atg7 deletion exhibit normal retinoid recycling, histology, and A2E accumulation, but display hypertrophy and cytosolic debris. Conclusion: Atg7 deficiency does not severely affect the health of RPE cells in mice. Significance: A2E accumulation and retinoid recycling are independent of Atg7-mediated autophagy in RPE cells. Autophagy is an evolutionarily conserved catabolic mechanism that relieves cellular stress by removing/recycling damaged organelles and debris through the action of lysosomes. Compromised autophagy has been implicated in many neurodegenerative diseases, including retinal degeneration. Here we examined retinal phenotypes resulting from RPE-specific deletion of the autophagy regulatory gene Atg7 by generating Atg7flox/flox;VMD2-rtTA-cre+ mice to determine whether autophagy is essential for RPE functions including retinoid recycling. Atg7-deficient RPE displayed abnormal morphology with increased RPE thickness, cellular debris and vacuole formation indicating that autophagy is important in maintaining RPE homeostasis. In contrast, 11-cis-retinal content, ERGs and retinal histology were normal in mice with Atg7-deficient RPE in both fasted and fed states. Because A2E accumulation in the RPE is associated with pathogenesis of both Stargardt disease and age-related macular degeneration (AMD) in humans, deletion of Abca4 was introduced into Atg7flox/flox;VMD2-rtTA-cre+ mice to investigate the role of autophagy during A2E accumulation. Comparable A2E concentrations were detected in the eyes of 6-month-old mice with and without Atg7 from both Abca4−/− and Abca4+/+ backgrounds. To identify other autophagy-related molecules involved in A2E accumulation, we performed gene expression array analysis on A2E-treated human RPE cells and found up-regulation of four autophagy related genes; DRAM1, NPC1, CASP3, and EIF2AK3/PERK. These observations indicate that Atg7-mediated autophagy is dispensable for retinoid recycling and A2E deposition; however, autophagy plays a role in coping with stress caused by A2E accumulation.
Etude du choix d'acquisition d'automobiles : Application du modèle probit multinomial bayésien à l'enquête « Parc Auto » (1997-2001)

Dans ce papier, nous effectuons une analyse comportementale du choix individuel des agents lors d'une nouvelle acquisition automobile. En croisant les trois variables binaires du niveau de gamme (haut ou bas), du carburant (gasoil ou supers), et de l'etat a l'achat (neuf ou occasion), huit types de voitures sont considerees comme alternatives concurrentes de choix. Pour caracteriser le comportement des acquereurs, nous ajustons la version bayesienne du Probit Multinomial (MNP) aux donnees francaises de « Parc Auto » (SOFRES). La methode d'estimation utilisee repose sur la version hybride de l'echantillonnage de Gibbs proposee par Nobile (1998). Exploitant les resultats avec le simulateur de frequence brute (CFS), nous effectuons une analyse ceteris paribus afin de determiner l'impact d'un changement de caracteristiques de l'agent et l'impact de la hausse du prix des carburants sur la repartition des probabilites de choix (ou des parts des marches) entre les differentes alternatives considerees.
The occurrence of multiple activities in the high-molecular-weight DNA polymerase fraction of mammalian tissues. A preliminary study of some of their properties.

The high-molecular-weight DNA polymerase fraction of calf thymus, rat liver or rat spleen can be resolved into further activities differing from one another in molecular weight and charge properties. The use of Sepharose 6B columns brings about partial resolution of these activities although DEAE-cellulose achieves a more effective separation. The high-molecular-weight fraction from calf thymus has so far yielded four species of activity, A, B, C and D sedimenting at 7.9 S, 5.2 S, 7.3 S and 6.0 S, respectively. In rat liver and spleen, 7.6-S (I), 7.23 (II) and 5-S enzymes have been detected although smaller and more variable amounts of 5-S enzyme occur in the rat tissues compared with calf thymus where the 5.2-5 species can represent 20–25%, of the total activity. There is no evidence for the presence of the 3.4-S enzyme in the partially purified fractions. All enzymes exhibit anomalous gel filtration behaviour; it is suggested that this is due to asymmetry of the molecules. The molecular weights for both calf and rat enzymes are drawn from the ranges 200000–225000, 155000–170000 and 100000–110000; since these are multiples of 50000–55000, a main band on dodecylsulphate-polyacrylamide gel electrophoresis of molecular weight 53000–54000 for one calf enzyme and one rat enzyme, is of special interest. Of the four calf thymus activities only enzyme D can utilise poly(dA) · (dT)10 to support [3H]dTMP incorporation. The pooled peaks of A, B and C from calf thymus all utilise poly(dT) · (A)10 to support [3H]dAMP incorporation. A, B and C of calf thymus have pH optima in the region of 7.8–8.1 whereas D had its pH optimum at pH 7.2; Enzymes I and II of rat liver disappear together with increasing age of the animal, and like A, B, C and D of calf thymus are especially sensitive to the level of salt in the assay.
“Let's Talk about Sex”: Discussions in Seniors' Online Communities

Abstract Seniors' online communities offer them a safe sphere for discussing sex-related concerns. This netnographic study explored the characteristics of sex-related discussions in such communities and followed online sex-related discussions that took place in 14 leading English language-based communities during one full year (2,534 posts). Analysis revealed that the discussions were simultaneously a source of valuable information and entertainment, and that they had an effect on members' attitudes and offline sexual behavior. Battles between the discussions' protagonists and antagonists provided additional “spice” to the rather amusing yet educational and beneficial discussions. Overall, results indicated that in a reality of limited alternatives for sex-related communication, seniors have found a channel to satisfy their needs for sex-related information and support.