Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel in vivo imaging shows up-regulation of death receptors by paclitaxel and correlates with enhanced antitumor effects of receptor agonist antibodies

Susceptibility to apoptosis by tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is mediated through cognate death receptor signaling. We hypothesized that auto-amplification of this apparatus would enhance antitumor effects in vivo and could be optimized using the results obtained from novel imaging techniques. We therefore imaged mice bearing human colorectal cancer (Colo205) tumor xenografts with HGS-ETR1 and HGS-ETR2 agonist antibodies to TRAIL receptor-1 (TRAIL-R1) and TRAIL-R2, respectively, after radiolabeling the antibodies. Paclitaxel significantly increased in vivo expression of TRAIL-R1 and TRAIL-R2 in a time-dependent manner. The imaging results were confirmed by immunoblots for steady-state protein levels (>20-fold increase in TRAIL-R1 and TRAIL-R2 levels in tumor xenografts by 48 h after paclitaxel administration). TRAIL-R1 and TRAIL-R2 mRNA expression did not change, suggesting that these effects were posttranscriptional. Sequential treatment with paclitaxel followed by HGS-ETR1 or HGS-ETR2 after 48 h resulted in markedly enhanced antitumor activity against Colo205 mouse xenografts. Our experiments suggest that sequential taxane treatment followed by TRAIL-R agonist antibodies could be applied in the clinic, and that novel imaging techniques using radiolabeled receptor antibodies may be exploitable to optimize sequence timing and patient selection. [Mol Cancer Ther 2006;5(12):2991–3000]
Glycosylation of closely spaced acceptor sites in human glycoproteins

Summary Asparagine-linked glycosylation of proteins by the oligosaccharyltransferase (OST) occurs when acceptor sites or sequons (N-x≠P-T/S) on nascent polypeptides enter the lumen of the rough endoplasmic reticulum. Metazoan organisms assemble two isoforms of the OST that have different catalytic subunits (STT3A or STT3B) and partially non-overlapping cellular roles. Potential glycosylation sites move past the STT3A complex, which is associated with the translocation channel, at the protein synthesis elongation rate. Here, we investigated whether close spacing between acceptor sites in a nascent protein promotes site skipping by the STT3A complex. Biosynthetic analysis of four human glycoproteins revealed that closely spaced sites are efficiently glycosylated by an STT3B-independent process unless the sequons contain non-optimal sequence features, including extreme close spacing between sequons (e.g. NxTNxT) or the presence of paired NxS sequons (e.g. NxSANxS). Many, but not all, glycosylation sites that are skipped by the STT3A complex can be glycosylated by the STT3B complex. Analysis of a murine glycoprotein database revealed that closely spaced sequons are surprisingly common, and are enriched for paired NxT sites when the gap between sequons is less than three residues.
Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice

Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 CAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)67 mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild‐type littermates. We show that GAD67 expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease.
Adaptive Changes in Life History and Survival following a New Guppy Introduction

Numerous studies of wild populations have shown that phenotypic traits can change adaptively on short timescales, but very few studies have considered coincident changes in major fitness components. We here examine adaptive changes in life‐history traits and survival rates for wild guppies introduced into new environments. Female life‐history traits in the derived (Damier River) populations diverged from the ancestral (Yarra River) population, as a result of adaptation to predation regime (high vs. low) and other aspects of the local river. Moreover, some components of the derived Damier populations, particularly juveniles, now show higher survival in the Damier than do contemporary representatives from the ancestral Yarra population. These results suggest that adaptive change can improve survival rates after fewer than 10 years (fewer than 30 guppy generations) in a new environment.
Asymptotic probabilities of languages with generalized quantifiers

The impact of adding certain families of generalized quantifiers to first-order logic (FO) on the asymptotic behavior of sentences is studied. All the results are stated and proved for languages disallowing free variables in the scope of generalized quantifiers. For a class K of finite structures closed under isomorphism, the quantifier Q/sub K/ is said to be strongly monotonic, sm, if membership in the class is preserved under a loose form of extensions. The first theorem (O/1 law for FO with any set of sm quantifiers) subsumes a previous criterion for proving that almost no graphs satisfy a given property. A O/1 law for FO with Hartig quantifiers (equicardinality quantifiers) and a limit law for a fragment of FO with Rescher quantifiers (expressing inequalities of cardinalities) are also established. It is also proved that the O/1 law fails for the extension of FO with Hartig quantifiers if the above syntactic restriction is relaxed, giving the best upper bound for the existence of a O/1 law for FO with Hartig quantifiers. <<ETX>>
Charles Mackay's Own Extraordinary Popular Delusions and the Railway Mania

Charles Mackay's book "Extraordinary Popular Delusions and the Madness of Crowds" enjoys extraordinarily high renown in the financial industry and among the press and the public. It also has an extraordinarily low reputation among historians.This paper argues that Mackay's sins of commission were dwarfed by his sins of omission. He lived through several giant investment manias in Britain, yet he did not discuss them in his books. An investigation of Mackay's newspaper writings shows that he was one of the most ardent cheerleaders for the Railway Mania, the greatest and most destructive of these episodes of extreme investor exuberance.Mackay's story provides another example of a renowned expert on bubbles who decides that "this time is different. " His moves through a sequence of delusions help explain the length and damage of the Railway Mania. He was a free market and technology enthusiast, and faced many issues that are important today, such as government ownership or regulation, interconnection, standardization, structural separation, and analogs to net neutrality. A crushing national debt and high unemployment in an economy pulling out of a deep depression (and in perceived danger of falling into another one) were very important in shaping attitudes towards railway expansion. The analogies and contrasts between Mackay's time and ours are instructive.
What Determines Permissiveness Toward Corruption?

Understanding citizen corruption permissiveness can help clarify whether a general willingness to fight corruption exists in a society. Using 2005-2007 World Values Survey data from six Latin American countries, an index measuring corruption permissiveness was constructed. Results suggest that permissiveness varies by country and is associated with age, education, ethnicity, cultural values, and confidence in public organizations.
A 4-Element Phased-Array System With Simultaneous Spatial- and Frequency-Domain Filtering at the Antenna Inputs

To reject strong interference in excess of 0 dBm, a 4- element LO-phase shifting phased-array receiver with 8-phase passive mixers terminated by baseband capacitors is presented. The passive mixers upconvert both the spatial and frequency domain filtering from baseband to RF, hence realizing blocker suppression directly at the antenna inputs. A comprehensive mathematical model provides a set of closed-form equations describing the spatial and frequency domain filtering including imperfections. A prototype is realized in 28 nm CMOS. It exploits third harmonic reception to achieve a wide RF-frequency range from 0.6-4.5 GHz at 34-119 mW power dissipation, while also providing impedance matching. Out of the band/beam, a 1 dB-compression point as high as +12/+10 dBm has been measured. The 1-element noise figure over the RF-frequency range is 4-6.3 dB, while in-beam/band IIP3 values of 0- +2.6 dBm are measured. This proposed technique can be instrumental to make RF receivers more robust for interference, while still being flexibly tunable in frequency.
Effect of Heating and Glycation on the Allergenicity of 2S Albumins (Ara h 2/6) from Peanut

Background Peanut allergy is one of the most common and severe food allergies, and processing is known to influence the allergenicity of peanut proteins. We aimed to establish the effect of heating and glycation on the IgE-binding properties and biological activity of 2S albumins (Ara h 2/6) from peanut. Methodology/Principal Findings Native Ara h 2/6 was purified from raw peanuts and heated in solution (15 min, 110°C) in the presence or absence of glucose. Ara h 2 and 6 were also purified from roasted peanut. Using PBMC and sera from peanut-allergic patients, the cellular proliferative potency and IgE reactivity (reverse EAST inhibition) and functionality (basophil degranulation capacity) of allergens were assessed. Heating Ara h 2/6 at 110°C resulted in extensive denaturation, hydrolysis and aggregation of the protein, whilst Ara h 2 and 6 isolated from roasted peanut retained its native conformation. Allergen stimulation of PBMC induced proliferation and Th2 cytokine secretion which was unaffected by thermal processing. Conversely, IgE reactivity and functionality of Ara h 2/6 was decreased by heating. Whilst heating-glycation further reduced the IgE binding capacity of the proteins, it moderated their loss of histamine releasing capacity. Ara h 2 and 6 purified from roasted peanut demonstrated the same IgE reactivity as unheated, native Ara h 2/6. Conclusions/Significance Although no effect of processing on T-cell reactivity was observed, heat induced denaturation reduced the IgE reactivity and subsequent functionality of Ara h 2/6. Conversely, Ara h 2 and 6 purified from roasted peanut retained the structure and IgE reactivity/functionality of the native protein which may explain the allergenic potency of this protein. Through detailed molecular study and allergenicity assessment approaches, this work then gives new insights into the effect of thermal processing on structure/allergenicity of peanut proteins.
Early Stage Influenza Detection from Twitter

Influenza is an acute respiratory illness that occurs virtually every year and results in substantial disease, death and expense. Detection of Influenza in its earliest stage would facilitate timely action that could reduce the spread of the illness. Existing systems such as CDC and EISS which try to collect diagnosis data, are almost entirely manual, resulting in about two-week delays for clinical data acquisition. Twitter, a popular microblogging service, provides us with a perfect source for early-stage flu detection due to its real- time nature. For example, when a flu breaks out, people that get the flu may post related tweets which enables the detection of the flu breakout promptly. In this paper, we investigate the real-time flu detection problem on Twitter data by proposing Flu Markov Network (Flu-MN): a spatio-temporal unsupervised Bayesian algorithm based on a 4 phase Markov Network, trying to identify the flu breakout at the earliest stage. We test our model on real Twitter datasets from the United States along with baselines in multiple applications, such as real-time flu breakout detection, future epidemic phase prediction, or Influenza-like illness (ILI) physician visits. Experimental results show the robustness and effectiveness of our approach. We build up a real time flu reporting system based on the proposed approach, and we are hopeful that it would help government or health organizations in identifying flu outbreaks and facilitating timely actions to decrease unnecessary mortality.
Informing Comprehensive HIV Prevention: A Situational Analysis of the HIV Prevention and Care Context, North West Province South Africa

Objective Building a successful combination prevention program requires understanding the community’s local epidemiological profile, the social community norms that shape vulnerability to HIV and access to care, and the available community resources. We carried out a situational analysis in order to shape a comprehensive HIV prevention program that address local barriers to care at multiple contextual levels in the North West Province of South Africa. Method The situational analysis was conducted in two sub-districts in 2012 and guided by an adaptation of WHO’s Strategic Approach, a predominantly qualitative method, including observation of service delivery points and in-depth interviews and focus groups with local leaders, providers, and community members, in order to recommend context-specific HIV prevention strategies. Analysis began during fieldwork with nightly discussions of findings and continued with coding original textual data from the fieldwork notebooks and a select number of recorded interviews. Results We conducted over 200 individual and group interviews and gleaned four principal social barriers to HIV prevention and care, including: HIV fatalism, traditional gender norms, HIV-related stigma, and challenges with communication around HIV, all of which fuel the HIV epidemic. At the different levels of response needed to stem the epidemic, we found evidence of national policies and programs that are mitigating the social risk factors but little community-based responses that address social risk factors to HIV. Conclusions Understanding social and structural barriers to care helped shape our comprehensive HIV prevention program, which address the four ‘themes’ identified into each component of the program. Activities are underway to engage communities, offer community-based testing in high transmission areas, community stigma reduction, and a positive health, dignity and prevention program for stigma reduction and improve communication skills. The situational analysis process successfully shaped key programmatic decisions and cultivated a deeper collaboration with local stakeholders to support program implementation.
Mast Cell Accumulation in Glioblastoma with a Potential Role for Stem Cell Factor and Chemokine CXCL12

Glioblastoma multiforme (GBM) is the most common and malignant form of glioma with high mortality and no cure. Many human cancers maintain a complex inflammatory program triggering rapid recruitment of inflammatory cells, including mast cells (MCs), to the tumor site. However, the potential contribution of MCs in glioma has not been addressed previously. Here we report for the first time that MCs infiltrate KRas+Akt-induced gliomas, using the RCAS/TV-a system, where KRas and Akt are transduced by RCAS into the brains of neonatal Gtv-a- or Ntv-a transgenic mice lacking Ink4a or Arf. The most abundant MC infiltration was observed in high-grade gliomas of Arf−/− mice. MC accumulation could be localized to the vicinity of glioma-associated vessels but also within the tumor mass. Importantly, proliferating MCs were detected, suggesting that the MC accumulation was caused by local expansion of the MC population. In line with these findings, strong expression of stem cell factor (SCF), i.e. the main MC growth factor, was detected, in particular around tumor blood vessels. Further, glioma cells expressed the MC chemotaxin CXCL12 and MCs expressed the corresponding receptor, i.e. CXCR4, suggesting that MCs could be attracted to the tumor through the CXCL12/CXCR4 axis. Supporting a role for MCs in glioma, strong MC infiltration was detected in human glioma, where GBMs contained significantly higher MC numbers than grade II tumors did. Moreover, human GBMs were positive for CXCL12 and the infiltrating MCs were positive for CXCR4. In conclusion, we provide the first evidence for a role for MCs in glioma.
American Religion: Contemporary Trends

List of Figures ix Acknowledgments xi Chapter 1: Introduction 1 Chapter 2: Diversity 16 Chapter 3: Belief 33 Chapter 4: Involvement 42 Chapter 5: Congregations 55 Chapter 6: Leaders 69 Chapter 7: Liberal Protestant Decline 81 Chapter 8: Polarization 94 Chapter 9: Conclusion 110 Notes 115 Index 137
Robust Expression of the Human Neonatal Fc Receptor in a Truncated Soluble Form and as a Full-Length Membrane-Bound Protein in Fusion with eGFP

Studies on the neonatal Fc receptor (FcRn) have revealed a multitude of important functions in mammals, including protection of IgG and serum albumin (SA) from lysosomal degradation. The pharmacokinetic behavior of therapeutic antibodies, IgG-Fc- and SA-containing drugs is therefore influenced by their interaction with FcRn. Pre-clinical development of such drugs is facilitated if their interaction with FcRn can be studied in vitro. For this reason we have developed a robust system for production of the soluble extracellular domain of human FcRn as well as the full-length receptor as fusion to green fluorescent protein, taking advantage of a lentivirus-based gene delivery system where stable over-expressing cells are easily and rapidly generated. Production of the extracellular domain in multiple-layered culture flasks, followed by affinity purification using immobilized IgG, resulted in capture of milligram amounts of soluble receptor per liter cell culture with retained IgG binding. The receptor was further characterized by SDS-PAGE, western blotting, circular dichroism spectroscopy, ELISA, surface plasmon resonance and a temperature stability assay showing a functional and stable protein of high purity. The full-length receptor was found to be successfully over-expressed in a membrane-bound form with retained pH-dependent IgG- and SA-binding.
Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of stroke

Autophagy is an important cellular recycling mechanism through self-digestion in responses to cellular stress such as starvation. Studies have shown that autophagy is involved in maintaining the homeostasis of the neural system during stroke. However, molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. Previously, we and others have shown that immune-related GTPase M (IRGM; termed IRGM1 in the mouse nomenclature) can regulate the survival of immune cells through autophagy in response to infections and autoimmune conditions. Here, using a permanent middle cerebral artery occlusion (pMCAO) mouse model, we found that IRGM1 was upregulated in the ischemic side of the brain, which was accompanied by a significant autophagic response. In contrast, neuronal autophagy was almost complete lost in Irgm1 knockout (KO) mice after pMCAO induction. In addition, the infarct volume in the Irgm1-KO pMCAO mice was significantly increased as compared to wild-type mice. Histological studies suggested that, at the early stage (within 24 h) of ischemia, the IRGM1-dependent autophagic response is associated with a protection of neurons from necrosis in the ischemic core but a promotion of neuronal apoptosis in the penumbra area. These data demonstrate a novel role of IRGM1 in regulating neuronal autophagy and survival during ischemic stroke.
An investigation of computational and informational limits in Gaussian mixture clustering

We investigate under what conditions clustering by learning a mixture of spherical Gaussians is (a) computationally tractable; and (b) statistically possible. We show that using principal component projection greatly aids in recovering the clustering using EM; present empirical evidence that even using such a projection, there is still a large gap between the number of samples needed to recover the clustering using EM, and the number of samples needed without computational restrictions; and characterize the regime in which such a gap exists.
THE DYNAMICAL BOREL-CANTELLI LEMMA FOR INTERVAL MAPS

The dynamical Borel-Cantelli lemma for some interval maps is considered. For expanding maps whose derivative has bounded variation, any sequence of intervals satisfies the dynamical Borel-Cantelli lemma. If a map has an indifferent fixed point, then the dynamical Borel-Cantelli lemma does not hold even in the case that the map has a finite absolutely continuous invariant measure and summable decay of correlations.
Stroke in South Asia: A Systematic Review of Epidemiologic Literature from 1980 to 2010

Background: Globally 15 million people have an acute stroke every year and one third of them die secondary to stroke events. Most research on stroke prevention and treatment is done in developed countries, yet more than 85% of strokes occur in developing countries. In particular, stroke remains an underrecognized cause of death and disability in South Asia. Methods: We conducted a systematic review to identify reliable and comparable epidemiological evidence on stroke in South Asia from 1980 to 2010. Publications were screened for eligibility to identify only population-based stroke studies. Results: Of the 71 studies retrieved, only 6 studies from South Asia gave us acceptable estimates of the burden of stroke. Population-based studies from South Asia have stroke prevalence in the range of 45–471 per 100,000. The age-adjusted incidence rate varied from approximately 145 per 100,000 to 262 per 100,000. Rural parts of South Asia have a lower stroke prevalence compared with urban areas. Conclusions: Our review highlights the paucity of research data in South Asia. This must be addressed in order to accurately determine the burden of stroke in South Asia, so that specific policy recommendations can be formulated to combat the stroke epidemic in this region.
Effect of dietary unsaturated and saturated fats on azoxymethane-induced colon carcinogenesis in rats.

The effects of dietary unsaturated and saturated fats on chemically induced colon carcinogenesis were examined in male Donryu rats. The rats were fed two types of semipurified diets consisting of 5% linoleic acid or 4.7% stearic acid plus 0.3% essential fatty acid as dietary fats. The rats were treated with azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and sacrificed 15 weeks after the last injection of the carcinogen. The rats fed unsaturated fat diet demonstrated a significantly higher incidence of colon tumors [100%], more tumors per rat [2.68 +/- 1.60 (S.D.)], and greater malignant differentiation histologically than did those fed saturated fat diet [76%, 1.79 +/- 1.59, respectively]. Lipid analysis of colon tumors and colon mucosa showed that unsaturated fat diet altered the phosphatide fatty acyl composition of colon mucosa markedly and increased the content of arachidonic acid in the neutral lipid of colon tumors. The altered lipid composition of the mucosa may increase the sensitivity of the colon to the carcinogen, and the excess of arachidonic acid or its metabolites may be the primary agents of cocarcinogenesis of colon tumors. These findings suggest that dietary unsaturated fats have potent cocarcinogenic effects on colon carcinogenesis.