Miracle-dz/UniFAR-FTUs huggingface dataset:
IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma.

UNLABELLED Dense fibrosis and a robust macrophage infiltrate are key therapeutic barriers in pancreatic ductal adenocarcinoma (PDAC). CD40 activation can circumvent these barriers by inducing macrophages, originating from peripheral blood monocytes, to deplete fibrosis. The precise mechanism and therapeutic implications of this antifibrotic activity, though, remain unclear. Here, we report that IFNγ and CCL2 released systemically in response to a CD40 agonist cooperate to redirect a subset of Ly6C(+)CCR2(+)monocytes/macrophages to infiltrate tumors and deplete fibrosis. Whereas CCL2 is required for Ly6C(+)monocyte/macrophage infiltration, IFNγ is necessary for tumor-infiltrating monocytes/macrophages to shift the profile of matrix metalloproteinases (MMP) in tumors, leading to MMP-dependent fibrosis degradation. In addition, MMP13-dependent loss of extracellular matrix components induced by a CD40 agonist increased PDAC sensitivity to chemotherapy. Our findings demonstrate that fibrosis in PDAC is a bidirectional process that can be rapidly altered by manipulating a subset of tumor-infiltrating monocytes, leading to enhanced chemotherapy efficacy. SIGNIFICANCE We report that CD40 agonists improve chemotherapy efficacy in pancreatic carcinoma by redirecting tumor-infiltrating monocytes/macrophages to induce fibrosis degradation that is dependent on MMPs. These findings provide novel insight into the plasticity of monocytes/macrophages in cancer and their capacity to regulate fibrosis and modulate chemotherapy efficacy in pancreatic carcinoma.
Symbolic Politics or Generiﬁcation ? The Ambivalent Implications of Tree Ordinations in the Thai Environmental Movement

Since the early 1990s, tree ordinations have become an important practice for some Thai environmental activists who seek greater legitimacy for local management and use of natural resources. This paper, explores the political and cultural effects of tree ordinations by applying the concepts of “cultural objectiﬁcation” and “cultural generiﬁcation. It argues that recent uses of tree ordinations depend on a process of cultural objectiﬁcation, facilitating the generiﬁcation of the ritual and its various components as an example of the larger category of “local wisdom. ” Signiﬁcant forms of power difference are implicated in the process. Middle class NGO activists largely controlled the practice and representation of the ritual and its symbols, and tended to objectify and simplify the values and practices of rural people. The tree ordinations of 1996-1997, dedicated to King Rama IX, had the further effect of symbolically bolstering the hierarchical structure of the Thai state and Thai society as a whole – a structure in which local leaders and middle class NGO activists exercise power as arbiters of “good” and “bad” culture among rural people. These are the ambiguous implications to which the title of this article refers: a process of objectiﬁcation and generiﬁcation and its place in the reproduction of a hierarchical political and cultural order, together with some decidedly positive outcomes of tree ordinations for the conservation and control of natural resources by rural people. Key words: Thailand, environmental activism, social hierarchy, power, cultural objectiﬁcation.
A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland

Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an essential tool for the study of breast cancer biology and for pre-clinical therapeutic development. While subcutaneous flank injections of cancer cells are widely used for studying breast cancer biology and for exploring novel therapies, orthotopic xenografting of tumors into the mouse mammary gland allow for the study of breast cancers in a biologically relevant microenvironment. In this study we report a modification of the method of orthotopic injections of cancer cells into the mouse mammary gland which greatly reduces the effects of surgery in mice including decreased wound size, procedure time and anesthesia. It also removes the risk of accidentally puncturing the peritoneal cavity. Consequently post-operative animal handling and stress are significantly reduced. All of these advantages are present without compromising procedure success rate. Therefore, this modification makes orthotopic mammary gland injection a more efficient procedure and greatly improves animal welfare.
Polarization of caveolins and caveolae during migration of immortalized neurons

During CNS development neurons undergo directional migration to achieve their adult localizations. To study neuronal migration, we used a model cell line of immortalized murine neurons (gonadotropin‐releasing hormone expressing neurons; GN11), enriched with caveolins and caveolae invaginations that show in vitro chemotaxis upon serum exposure. Cholesterol depletion with methyl‐β‐cyclodextrin induced the loss of caveolae and the inhibition of chemotaxis, thus suggesting that GN11 migration depends upon the structural integrity of caveolae. Polarization of proteins and organelles is a hallmark of cell migration. Accordingly, GN11 cells transmigrating through filter pores exhibited a polarized distribution of caveolin‐1 isoform (cav‐1) in the leading processes. In contrast, during two‐dimensional migration cav‐1 and caveolae polarized at the trailing edge. As caveolae are enriched with signaling molecules, we suggest that asymmetrical localization of caveolae may spatially orient GN11 neurons to incoming migratory signals thereby transducing them into directional migration.
Doing postgraduate research

Introduction - Martin Le Voi and Stephen Potter Getting Going - Stephen Potter Planning and Organizing a Research Project - David Wield et al The Writing Process - Andrew Ward Undertaking a Topic Review - Stephen Potter Using Computers in Research - Martin Le Voi Responsibilities, Rights and Ethics - Martin Le Voi The Examination Process and the Viva - Stephen Potter with Contributions from Professor John Swift
Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Significance We addressed the basic mechanisms underlying synapse heterogeneity, and we identified a form of regulation that serves to increase the variations in the efficacy with which neurons communicate with each other through synapses. We demonstrate that this process requires astrocytes, which, previously, have been thought to play mostly a passive role in maintaining neuronal functions. The cellular mechanism that regulates synaptic efficacy requires astrocyte membrane depolarization, activation of astrocyte NMDA receptors, and astrocyte calcium signaling. The fundamental nature of the regulation is underscored by the preservation of the mechanism from acute brain slices down to dissociated cultures that lack the native topology of brain networks. Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-d-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca2+ channels. Intracellular infusion of NMDARs or Ca2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocyte-dependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.
"A Definition at Last, but What Does It All Mean?"—Newspaper Coverage of the USDA Organic Seal and its Effects on Food Purchases-

This paper estimates the effects of media coverage in organic food production and the National Organic Program (NOP) on food purchases. Information from several independent data sources is complied into a unique data set that directly links national and local newspaper coverage to fluid milk consumption. An analysis of weekly store-level scanner data in a difference-in-differences approach suggests average increases in organic milk sales relative to conventional milk sales of 5 percent during weeks for which relevant news coverage is observed. Increases in intensity of news coverage, measured by the number of articles in a given week, are further found to increase the relative difference in sales but at a decreasing rate. However, these effects are found to dissipate quickly in the weeks following news coverage. Differentiating by context of observed articles suggests that product category specific coverage doubles observed increases in sales when compared to general coverage, while critical national and local coverage does not result in significant changes in organic milk sales. Furthermore, local news coverage seems to have a relatively higher impact than national news coverage, with increases in circulation of one local newspaper resulting in increased organic milk sales as well. Our results provide valuable insights for the evaluation of existing labeling regulations and future regulations on specialty foods in this context.
An Examination of the Psychometric Properties of the Test of Reading Performance Using Structural Equation Modeling

The present purpose was to investigate the psychometric properties of the Test of Reading Performance, a new scale designed to evaluate the reading performance of Greek elementary school students. The sample consisted of 181 elementary school students, attending Grades 1–6 at two elementary schools in the area of Thessaloniki. The Test of Reading Performance was hypothesized to measure six constructs, namely, letter knowledge, phoneme blending, word identification, morphology knowledge, syntactic knowledge, and passage comprehension. Each construct was defined by two to four measured variables. The chosen structural model supported the multidimensional nature of reading and the relationship between the measured variables and constructs. Estimates of discriminant and convergent validity using confirmatory factor analytic procedures were satisfactory although these was multicollinearity for the measures morphology-syntax and morphology-comprehension. Internal consistency was also satisfactory for the full scale (α = .83).
An Approach for Optimal Hierarchical Mobility, Management Network Architecture

The focus of this paper is to get the optimal hierarchical mobility management solution for next generation wireless IP-based networks. Hierarchical architectures prove advantageous in minimizing signaling overhead by limiting registration signaling locally. Our ultimate goal is to find the optimum hierarchy level, which should provide best performance in terms of networks parameters like signaling overhead, handoff latency and frequency of location updates. For this purpose an n-tiered architecture has been considered and optimality test on the number of tiers has been performed through analytical and ns-2 based simulation results. From the performance evaluation it is seen that time-bandwidth product is minimum for three-tiered network architecture leading as the optimal solution
Modeling and E-M Estimation of Haplotype-Specific Relative Risks from Genotype Data for a Case-Control Study of Unrelated Individuals

The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the R2h criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well.
User Selection Schemes for MIMO Broadcast Channels with Limited Feedback

We propose a user selection algorithm and the supporting feedback scheme, for MIMO Gaussian broadcast channels with arbitrary number of users, transmit beamforming and limited channel state information (CSI) available at the transmitter. The method relies on estimation of the user signal-to-interference-plus-noise ratios (SINR's) at the transmitter, by means of an appropriate finite-rate channel report from the mobiles. The basic principle is that users are added successively only if they are beneficial to the system in terms of increased throughput. Numerical results show improved performance compared to other finite-rate feedback schemes.
Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-α-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08±0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1±20.8 and 78.4±33.9 ng/mL/h, respectively, were lower than that from GB, 492±141 ng/mL/h (P<.05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765±50, 1035±202, and 957±227 ng/mL/h, respectively (P<.05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity.
Studying Relations Between E-learning Resources to Improve the Quality of Searching and Recommendation

Searching and recommendation are basic functions that effectively assist learners to approach their favorite learning resources. Several searching and recommendation techniques in the Information Retrieval (IR) domain have been proposed to apply in the Technology Enhanced Learning (TEL) domain. However, few of them pay attention on particular properties of e-learning resources, which potentially improve the quality of searching and recommendation. In this paper, we propose an approach that studies relations between e-learning resources, which is a particular property existing in online educational systems, to support resource searching and recommendation. Concretely, we rank e-learning resources based on their relations by adapting the Google's PageRank algorithm. We integrate this ranking into a text-matching search engine to refine the search results. We also combine it with a content-based recommendation technique to compute the similarity between user profile and e-learning resources. Experimental results on a shared dataset showed the efficiency of our approach.
Examining the mediating effect of positive moods on trust repair in e-commerce

Purpose – The purpose of this research is to investigate the impact of causal attributions (locus, stability, and controllability attributes) on trust violations and the coping strategies (affective, functional, and informational initiatives) involved in trust repair on building positive moods within the context of e‐commerce.Design/methodology/approach – The research model is tested using data collected from 513 active e‐shoppers. Structure equation modeling is employed to verify and validate the research model.Findings – Results show that strategies for repairing trust are effective in building positive moods among consumers, while causes of negative events have a negative impact on consumer mood. Furthermore, positive moods significantly influence the rebuilding of consumer trust. This research demonstrates that positive mood is an important mediator in trust repair.Practical implications – The research results provide insight into how e‐vendors can ease the tension associated with trust‐related disput.
Pulse radiation from a leaky-wave antenna

The paper investigates pulse radiation from a leaky-wave antenna (LWA). A semi-analytical model is developed to compute the far-field produced by an arbitrary pulse excitation and this model is validated by full-wave simulation. The study demonstrates that both angular dispersion and time dispersion lead to pulse distortion and that their effect become increasingly problematic with increasing antenna length.
Transposon-lnduced lnversion in Antirrhinum Modifies niwea Gene Expression To Give a Nove1 Flower Color Pattern under the Control of cycloídea

The nivea (niv) gene of Antirrhinum majus encodes chalcone synthase, an enzyme involved in synthesis of anthocyanin pigments. The nivfeC:98 allele contains a single copy of the transposon Tamd inserted at the niv locus. A large chromosomal rearrangement derived from this mutant has been shown to be flanked by two copies of Tam3. In this study, we compared sequences involved in this rearrangement with their progenitor sequences and concluded that the rearrangement is an inversion resulting from an aberrant transposition occurring shortly after replication of Tam3 that left both copies of Tam3 active after the rearrangement. Excision of Tam3 from its position adjacent to the niv coding region resulted in a novel distribution of anthocyanin pigment in the flower tube, caused by the interaction of the new sequences with the remnant of the niw promoter. The new sequences upstream of niv serve both to enhance niv transcription and to redirect the pattern of gene expression, placing niw under the control of the gene cycloideafad'afls, which determines the morphogenetic polarity of the flower.
‘The great unmentionable’: Exploring the pleasures and benefits of ecstasy from the perspectives of drug users

Although legal and illegal drugs have throughout history given pleasure to those who consume them, research in the drug field has ignored this central and fundamental feature. The absence of any discussion of pleasure is striking when one considers the contemporary literature on ecstasy and the dance scene. Pleasure is still missing within much of this drug discourse. Research has failed to explore a significant and integral feature of drug use, primarily the reasons why people use and the benefits they receive. To adjust this imbalance, the aim of this paper is to explore the ways in which young people experience and talk about the pleasure, enjoyment, and benefits of using ecstasy. Utilizing recent theoretical developments in both sociology and cultural studies, we examine in-depth qualitative interview data from a sample of 276 respondents who use ecstasy and attend dance events in the San Francisco Bay Area. We explore two different but interwoven themes that emerge from their narratives. First, the pleasures experienced from the immediate effects of the drug, and second, the more enduring benefits. The former enabled them to transcend the mundane nature of their everyday activities and interactions, and the latter resulted from the respondents’ belief that they could recreate elements of the ecstasy experience in their day-to-day lives. Basically that's how I could describe it, a pleasure overload. (018) All my friends say like, you know, I get very, very friendly. They say like they look at me and they think that I’ve got like sunshine flying out of my butt. Like I’m so happy. It's like … I can’t be any more happy. (036)