Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV / AIDS prevention and care among especially vulnerable young people: a framework for action.

This timely review of evidence for action identifies some of the priority issues facing such groups and the steps that must be taken to develop and scale up a meaningful response. It points to five principles in particular that should be central to future work at national or local level. First it is necessary to place the young person and her or his needs and experiences at the centre of our work. Second steps must be taken to ensure meaningful participation in programme and project design and development. Third the most successful approaches are those that work with a commitment to protecting and promoting the rights of young people. Fourth a clear gender focus must be present if the needs and interests of young women and young men are to be respected. Finally we must work to tackle both societal vulnerability and individual risk in our prevention efforts. The evidence is clear that one approach on its own is simply not enough. (excerpt)
Differential rotation in rapidly rotating F-stars ,

We obtained high quality spectra of 135 stars of spectral types F and later and derived "overall" broadening functions in selected wavelength regions utilizing a Least Squares Deconvolution (LSD) procedure. Precision values of the projected rotational velocity v sini were derived from the first zero of the Fourier transformed profiles and the shapes of the profiles were analyzed for effects of differential rotation. The broadening profiles of 70 stars rotating faster than v sini = 45 km s −1 show no indications of multiplicity nor of spottedness. In those profiles we used the ratio of the first two zeros of the Fourier transform q2/q1 to search for deviations from rigid rotation. In the vast majority the profiles were found to be consistent with rigid rotation. Five stars were found to have flat profiles probably due to cool polar caps, in three stars cuspy profiles were found. Two out of those three cases may be due to extremely rapid rotation seen pole on, only in one case (v sini = 52 km s −1 ) is solar-like differential rotation the most plausible explanation for the observed profile. These results indicate that the strength of differential rotation diminishes in stars rotating as rapidly as v sini > 50 km s −1 .
Essay in R&D, investment and growth

This paper presents a standard endogenous growth framework in which the source of growth is represented by vertical innovation. The crucial assumption we introduce is that there is a positive information gap concerning the discovery of innovation. The aim of reducing the information dissemination lag provides incentives for firms to decide to merge their research efforts. At the same time we find that the skilled/unskilled wage gap is strongly related to this phenomenon. We prove that changing antitrust attitudes toward efficienc-motivated mergers in contestable industries may simultaneously explain observed changes in the industry structure, in qualitative innovation, in wage inequality, and in labor supply composition.
Structural Insight into Inhibitor of Apoptosis Proteins Recognition by a Potent Divalent Smac-Mimetic

Genetic alterations enhancing cell survival and suppressing apoptosis are hallmarks of cancer that significantly reduce the efficacy of chemotherapy or radiotherapy. The Inhibitor of Apoptosis Protein (IAP) family hosts conserved proteins in the apoptotic pathway whose over-expression, frequently found in tumours, potentiates survival and resistance to anticancer agents. In humans, IAPs comprise eight members hosting one or more structural Baculoviral IAP Repeat (BIR) domains. Cellular IAPs (cIAP1 and 2) indirectly inhibit caspase-8 activation, and regulate both the canonical and the non-canonical NF-κB signaling pathways. In contrast to cIAPs, XIAP (X chromosome-linked Inhibitor of Apoptosis Protein) inhibits directly the effector caspases-3 and -7 through its BIR2 domain, and initiator caspase-9 through its BIR3 domain; molecular docking studies suggested that Smac/DIABLO antagonizes XIAP by simultaneously targeting both BIR2 and BIR3 domains. Here we report analytical gel filtration, crystallographic and SAXS experiments on cIAP1-BIR3, XIAP-BIR3 and XIAP-BIR2BIR3 domains, alone and in the presence of compound 9a, a divalent homodimeric Smac mimetic. 9a is shown to bind two BIR domains inter- (in the case of two BIR3) and intra-molecularly (in the case of XIAP-BIR2BIR3), with higher affinity for cIAP1-BIR3, relative to XIAP-BIR3. Despite the different crystal lattice packing, 9a maintains a right handed helical conformation in both cIAP1-BIR3 and XIAP-BIR3 crystals, that is likely conserved in solution as shown by SAXS data. Our structural results demonstrate that the 9a linker length, its conformational degrees of freedom and its hydrophobicity, warrant an overall compact structure with optimal solvent exposure of its two active moieties for IAPs binding. Our results show that 9a is a good candidate for pre-clinical and clinical studies, worth of further investigations in the field of cancer therapy.
Moderating Factors of Immediate, Dynamic, and Long-run Cross-Price Effects

In this article the authors describe their comprehensive analysis of moderating factors of cross-brand effects of price changes and contribute to the literature in five major ways. (1) They consider an extensive set of potential variables influencing cross-brand effects of price changes. (2) They examine moderators for the immediate as well as the dynamic cross-price effect. (3) They decompose price into regular and promotional price and study both cross-price effects separately. (4) They compare their findings with previous literature on the moderating factors of own-price effects to understand which factors influence own-price elasticity through affecting brand switching. (5) The authors use an advanced Bayesian estimation technique. The results show evidence of the neighborhood price effect and suggest that it is conditional on whether the promoted brand is priced above or below its competitor. The promoted brand's activities turn out to play a much more important role in determining the cross-price promotional effects than its competitor's similar activities. The authors outline conditions when cross-brand post-promotion dips tend to occur. Finally, they argue that the brand choice portion of the overall own-brand effect of a promotion depends on the brand's marketing strategy and on category-specific characteristics.
Tracking collaboration: forest planning and local participation on the San Juan National Forest, Colorado

The proliferation of community-based collaborative approaches to public land management and planning has spawned many questions regarding issues of community representation and the effects of participation for local residents. This paper presents a longitudinal assessment of local resident participation in collaborative forest planning on local community–forest relations in southwestern Colorado. Using survey data of participants involved in the San Juan National Forest's forest plan revision community study groups from 1998 to 2003, we assess participation in terms of community representation and the effects of community-based collaboration upon individuals' forest uses, forest values, and the level and form of involvement in forest management and planning activities. Results show that community representation remains slanted towards existing active stakeholders, and that while forest values, uses, and frequencies of involvement change little, participants cite positive effects in terms of the development of new knowledge, personal relationships, and greater confidence to engage in forest management affairs.
Municipal Tax Competition in Sweden : A regional approach

When jurisdictions on the same governmental level compete over the same tax base, inefficiencies occurs by setting taxes too low. This paper considers the horizontal tax competition in Swedish municipalities, and especially if there exist regional differences in this context. The period 2000 to 2011 is analyzed in three regions (the whole Sweden, the metropolitan municipalities and Norrland) using spatial econometrics with an instrumental variables approach. A spatial coefficient measuring strategic interactions, such as tax competition, is estimated which measures the spatial interaction in each sample. The results suggest that strategic tax setting is indeed present in all regions. However, when comparing the parameter estimates there is no evidence that this kind of behavior differs between regions.
REACTIVE SPLENOMEGALY AND VARIATION OF LYMPHOID-PLASMA CELL POPULATION ASSOCIATED WITH A MOUSE PITUITARY THYROTROPIC TUMOR.

Summary A transplantable thyrotropic pituitary tumor, subline L24a, which grew after 13 months of dormancy in an intact mouse was associated in its early passage with a variety of lymphoid tumors. On subsequent passage, slow growth over a 6- to 12-month period was regularly accompanied by striking splenomegaly without lymphoid or thymic neoplasia. The enlargement was due to a great increase in cells of the lymphoid series in the red pulp without loss of splenic architecture. In thyroidectomized mice plasma cells with many Russell bodies were especially numerous, and these cells were found in hypertrophied lymphoid follicles within other organs. It is suggested that the splenomegaly and, in earlier passage the lymphoid tumors, may represent an exaggerated antibody response to a tumor9s having unusual or abnormal hormonal activity. The transplanted pituitary tumors, in turn, showed severe hemorrhagic degeneration with peripheral small lymphocyte stasis in the lymphatics.
Genome wide analysis of Cyclophilin gene family from rice and Arabidopsis and its comparison with yeast

Cyclophilin proteins are the members of immunophillin group of proteins, known for their property of binding to the immune-suppressant drug cyclosporin A, hence named as cyclophilins. These proteins are characterized by the presence of peptidyl prolyl isomerase (PPIase) domain which catalyzes the cis-trans isomerisation process of proline residues. In the present study, an in-silico based approach was followed to identify and characterize the cyclophilin family from rice, Arabidopsis and yeast. We were able to identify 28 rice, 35 Arabidopsis and 8 yeast cyclophilin genes from their respective genomes on the basis of their annotation as well as the presence of highly conserved PPIase domain. The evolutionary relationship of the cyclophilin genes from the three genomes was analyzed using the phylogenetic tree. We have also classified the rice cyclophilin genes on the basis of localization of the protein in cell. The structural similarity of the cyclophilins was also analyzed on the basis of their homology model. The expression analysis performed using Genevestigator revealed a very strong stress responsive behavior of the gene family which was more prominent in later stages of stress. The study indicates the importance of the gene family in stress response as well as several developmental stages thus opening up many avenues for future study on the cyclophilin proteins.
Structure-Function Relationship in DNA Sequence Recognition by Transcription Factors

Transcription factors play essential role in the gene regulation in higher organisms, binding to multiple target sequences and regulating multiple genes in a complex manner. In order to understand the molecular mechanism of target recognition, and to predict target genes for transcription factors at the genome level, it is important to analyze the relationship between the structure and function (specificity) of transcription factors. We have used a knowledge-based approach, utilizing rapidly increasing structural data of protein-DNA complexes, to derive empirical potential functions for the specific interactions between bases and amino acids as well as for DNA conformation, from the statistical analyses on the structural data. Then these statistical potentials are used to quantify the specificity of protein-DNA recognition. The quantification of specificity has enabled us to establish the structure-function analysis of transcription factors, such as the effects of binding cooperativity on target recognition. The method is also applied to real genome sequences, predicting potential target sites. We are also using computer simulations of protein-DNA interactions in order to complement the empirical method. Combining the two approaches together, we can better understand the mechanism of protein-DNA recognition and improve the target prediction of transcription factors.
Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK Receptor DNAM-1

Human induced pluripotent stem cells (hiPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, iPSC-derived grafts are at risk of giving rise to teratomas in the host, if residuals of tumorigenic cells are not rejected by the recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK cells killed hiPSC lines efficiently (P=1.69x10-39). Notably, the specific lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly different (P=1.72x10-6) and ranged between 46 % and 64 % in 51Cr-release assays when compared to K562 cells. The hiPSC lines were killed by both allogeneic and autologous NK cells although autologous NK cells were less efficient (P=8.63x10-6). Killing was partly dependent on the activating NK receptor DNAM-1 (P=8.22x10-7). The DNAM-1 ligands CD112 and CD155 as well as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts of human leukocyte antigen (HLA) class I proteins, which serve as ligands for inhibitory and activating NK receptors were also detected. Thus, the susceptibility to NK cell killing appears to constitute a common feature of hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even after autologous transplantations of pluripotent stem cell-derived grafts that contain traces of pluripotent cells.
Transcriptome Profiling and Functional Analyses of the Zebrafish Embryonic Innate Immune Response to Salmonella Infection1

Due to the clear separation of innate immunity from adaptive responses, the externally developing zebrafish embryo represents a useful in vivo model for identification of innate host determinants of the response to bacterial infection. Here we performed a time-course transcriptome profiling study and gene ontology analysis of the embryonic innate immune response to infection with two model Salmonella strains that elicit either a lethal infection or an attenuated response. The transcriptional response to infection with both the lethal strain and the avirulent LPS O-Ag mutant strain showed clear conservation with host responses detected in other vertebrate models and human cells, including induction of genes encoding cell surface receptors, signaling intermediates, transcription factors, and inflammatory mediators. Furthermore, our study led to the identification of a large set of novel immune response genes and infection markers, the future functional characterization of which will support vertebrate genome annotation. From the time series and bacterial strain comparisons, matrix metalloproteinase genes, including mmp9, were among the most consistent infection-responsive genes. Purified Salmonella flagellin also strongly induced mmp9 expression. Using knockdown analysis, we showed that this gene was downstream of the zebrafish homologs of the flagellin receptor TLR5 and the adaptor MyD88. Additionally, flagellin-mediated induction of other inflammation markers, including il1b, il8, and cxcl-C1c, was reduced upon Tlr5 knockdown as well as expression of irak3, a putative negative TLR pathway regulator. Finally, we showed that induction of il1b, mmp9, and irak3 requires Myd88-dependent signaling, while ifn1 and il8 were induced Myd88 independently during Salmonella infection.
Visualization of APP dimerization and APP‐Notch2 heterodimerization in living cells using bimolecular fluorescence complementation

We previously demonstrated that the amyloid precursor protein (APP) interacts with Notch receptors. Here, we confirmed the APP/Notch1 endogenous interaction in embryonic day 17 rat brain tissue, suggesting the interaction was not as a result of over‐expression artifacts. To investigate potential homodimeric and heterodimeric interactions of APP and Notch2 (N2), we have visualized the subcellular localization of the APP/N2 complexes formed in living cells using bimolecular fluorescence complementation (BiFC) analysis. BiFC was accomplished by fusing the N‐terminal fragment or the C‐terminal fragment of yellow fluorescent protein (YFP) to APP, N2, and a C‐terminally truncated form of N2. When expressed in COS‐7 cells, these tagged proteins alone did not produce a fluorescent signal. The tagged APP homodimer produced a weak fluorescent signal, while neither full‐length N2, nor a truncated N2 alone, produced a visible signal, suggesting that N2 receptors do not form homodimers. The strongest fluorescent signal was obtained with co‐expression of the C‐terminal fragment of YFP fused to APP and the N‐terminal fragment of YFP fused to the truncated form of N2. This heterodimer localized to plasma membrane, endoplasmic reticulum (ER), Golgi and other compartments. The results were confirmed and quantified by flow cytometry. The BiFC method of specifically visualizing APP/Notch interactions can be applied to study APP and Notch signaling during development, aging and neurodegeneration.
Node location estimation scheme in wireless sensor networks based on support vector regression

In view of the issue that the accuracy of the node location of wireless sensor networks (WSN) is low by adopting maximum likelihood estimation (MLE) in estimating the measurement information value with big noise, a new node location estimation scheme based on support vector regression (SVR-NLE) is proposed. Through learning the relation between the real value of trilateral and node coordinate, this method utilizes the generalization capability of SVR (support vector regression) to achieve better location on the same noise level. The experiments choose LS-SVR (least squares SVR) and epsiv - SVR ( epsiv -insensitive SVR) to estimate the location of 100 randomly distributed unknown nodes. The result indicates that this new method can improve 15-20% location accuracy than MLE.
Cutting Edge: Immunosuppressant as Adjuvant for Tolerogenic Immunization1

Vaccination for autoimmune and alloimmune diseases has long been an attractive idea. Yet, there is no suitable adjuvant to forcefully steer the immune response toward tolerance. In this study we show that dexamethasone, a potent glucocorticoid immunosuppressant, can function as a tolerogenic adjuvant when applied together with peptide immunogen. BALB/c mice with pre-established delayed-type hypersensitivity to hen OVA were immunized with an OVA-derived, MHC II-restricted peptide (OVA323–339) in the presence of dexamethasone. The treatment caused long-term desensitization in treated animals to hen OVA via a dexamethasone-dependent tolerogenic mechanism that blocks maturation of dendritic cells and expands OVA323–339-specific CD4+CD25+Foxp3+ regulatory T cells in vivo. Similar treatment of NOD mice using dexamethasone and an insulin-derived, MHC II-restricted peptide (B:9–23) prevented predisposed spontaneous diabetes. Remarkably, in both models, dexamethasone-augmented immunization induced long-term persistent, Ag-specific regulatory T cells responsive to recall Ags. These results reveal for the first time the potential usefulness of immunosuppressants as tolerogenic adjuvants.
The H19 Non-Coding RNA Is Essential for Human Tumor Growth

Background Mutations and epigenetic aberrant signaling of growth factors pathways contribute to carcinogenesis. Recent studies reveal that non-coding RNAs are controllers of gene expression. H19 is an imprinted gene that demonstrates maternal monoallelic expression without a protein product; although its expression is shut off in most tissues postnatally, it is re-activated during adult tissue regeneration and tumorigenesis. Moreover, H19 is highly expressed in liver metastasis derived from a range of carcinomas. The objective of this study is to explore the role of H19 in carcinogenesis, and to determine its identification as an anti-tumor target. Methodology/ Principle Findings By controlling oxygen pressure during tumor cell growth and H19 expression levels, we investigated the role of H19 expression in vitro and in vivo in hepatocellular (HCC) and bladder carcinoma. Hypoxia upregulates the level of H19 RNA. Ablations of tumorigenicity of HCC and bladder carcinomas in vivo are seen by H19 knockdown which also significantly abrogates anchorage-independent growth after hypoxia recovery, while ectopic H19 expression enhances tumorigenic potential of carcinoma cells in vivo. Knocking-down H19 message in hypoxic stress severely diminishes p57kip2 induction. We identified a number of potential downstream targets of H19 RNA, including angiogenin and FGF18. Conclusions H19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy.
The Effects of Traditional and Electronic Word-of-Mouth on Destination Image: A Case of Vacation Tourists Visiting Branson, Missouri

The effects of integrated word-of-mouth (WOM), both traditional and electronic, on tourism products are yet to be fully investigated. The current study aims to assess the effects of and differences between traditional WOM and electronic WOM, between personal WOM and commercial WOM, and between positive and negative WOM on a destination image. Results of the study indicate that traditional WOM had a greater influence on destination image compared to electronic WOM. Personal traditional WOM had a greater influence on destination image compared to electronic personal WOM and commercial WOM. However, negative WOM exerted less influence on the destination’s image compared to positive WOM while negative electronic WOM had a greater influence on destination image compared to negative traditional WOM.
Attention-deficit hyperactivity disorder and life-span development

Developmentally inappropriate degrees of hyperactivity, inattention and impulsivity are common symptoms in childhood. If of early onset (before 7 years), present in different settings and to a degree that causes functional impairment, a diagnosis of attention-deficit hyperactivity disorder (ADHD) or ‘hyperkinetic disorder’ should be considered. The age criterion is crucial to distinguish ADHD and hyperkinetic disorder from later-onset conditions such as agitated depression, adolescent-onset socialised conduct disorder (probably not linked to ADHD) or hypomania, that might appear superficially similar. Attention-deficit hyperactivity disorder and hyperkinetic disorder are commonly associated with language, learning and social impairments. Indeed, in severe cases hyperactivity could be a marker of a multifaceted developmental disorder. Hence, competent assessment usually requires a thorough history, often using a number of sources.
Expected Bequests and Their Distribution

Based on a sample of actual bequests that is population-representative and on the subjective probability of bequests, we estimate the distribution of bequests that the older population will make. We find that the distribution is highly skewed, so that the typical baby-boom person will receive a very modest inheritance. This is partly due to the skewed distribution of wealth and partly due to the tendency of the wealthy to have fewer children. But it is also due to anticipated dissaving: we estimate that households in the age band 70-74 will bequeath just 39% of their wealth, consuming the rest before they die.