Miracle-dz/UniFAR-FTUs huggingface dataset:
CYLD Inhibits Tumorigenesis and Metastasis by Blocking JNK/AP1 Signaling at Multiple Levels

CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear. Here, we showed that K14-driven epidermal expression of a patient-relevant and catalytically deficient CYLD truncated mutant (CYLDm) sensitized mice to skin tumor development in response to 7,12-dimethylbenz[α]anthracene (DMBA)/(12-O-tetradecanoylphorbol-13-acetate) TPA challenge. Tumors developed on transgenic mice were prone to malignant progression and lymph node metastasis and displayed increased activation of c-Jun-NH2-kinase (JNK) and the downstream c-Jun and c-Fos proteins. Most importantly, topical application of a pharmacologic JNK inhibitor significantly reduced tumor development and abolished metastasis in the transgenic mice. Further in line with these animal data, exogenous expression of CYLDm in A431, a human squamous cell carcinoma (SCC) cell line, markedly enhanced cell growth, migration, and subcutaneous tumor growth in an AP1-depdendent manner. In contrast, expression of the wild-type CYLD inhibited SCC tumorigenesis and AP1 function. Most importantly, CYLDm not only increased JNK activation but also induced an upregulation of K63 ubiquitination on both c-Jun and c-Fos, leading to sustained AP1 activation. Our findings uncovered c-Jun and c-Fos as novel CYLD targets and underscore that CYLD controls epidermal tumorigenesis through blocking the JNK/AP1 signaling pathway at multiple levels. Cancer Prev Res; 4(6); 851–9. ©2011 AACR.
Open Access Research Article Comparative Age Distribution of Influenza Morbidity and Mortality during Seasonal Influenza Epidemics and the 2009 H1n1 Pandemic

article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Several studies have shown a relatively high mortality rate among young people infected by the 2009 pandemic influenza A (H1N1) virus. Here we compared the age distributions of morbidity and mortality during two seasonal influenza epidemics (H1N1 and H3N2) in France and the United States with those of the 2009 H1N1 pandemic waves in the same countries. Methods: Age-standardized ratios were used to compare the age distribution of morbidity and mortality due to influenza between the two countries and across the different years. Non parametric analysis of variance was used to compare these ratios between epidemic and pandemic influenza. Results: Age distribution of morbidity was similar between the 2009 pandemic and seasonal epidemics due to H1N1 (p = 0.72) and H3N2 viruses (p = 0.68). In contrast, the proportion of under-60s among influenza deaths was markedly higher during the 2009 pandemic (peak <20 years) than during the seasonal epidemics (respectively p = 0.007 and p = 0.0008). Background The 2009 pandemic influenza A (H1N1) virus (2009 pH1N1) emerged in April 2009 in the Americas and subsequently spread worldwide [1]. Preliminary findings in Mexico and the United States suggested that people aged from 5 to 30 years were at a higher risk of infection, while those aged 30 to 50 years old were at a higher risk of death [2-4]. The risk of infection and death seemed to be lower in the elderly population, a finding attributed to prior exposure to A/H1N1 viruses that circulated before 1957 [5,6]. During seasonal epidemics, mortality is classically highest in the elderly population. Conversely, during pandemic influenza mortality is highest in younger age groups. This shift of mortality toward younger age groups is considered as a signature feature of pandemics [7]. Few comparative studies are available on age distribution of morbidity during pandemic and seasonal influenza. Studies of the 1918, 1957 and 1968 pandemics suggest that the
Macrophage Polarization: Convergence Point Targeted by Mycobacterium Tuberculosis and HIV

In the arms race of host–microbe co-evolution, macrophages (Mɸs) have been endowed with strategies to neutralize pathogenic challenge while preserving host integrity. During steady-states conditions, Mɸs perform multiple house-keeping functions governed by their differentiation state, tissue distribution, and signals from the microenvironment. In response to pathogenic challenge and host mediators, however, Mɸs undergo different programs of activation rendering them either pro-inflammatory and microbicidal (M1), or immunosuppressants and tissue repairers (M2). An excessive or prolonged polarization of either program may be detrimental to the host due to potential tissue injury or contribution to pathogenesis. Conversely, intracellular microbes that cause chronic diseases such as tuberculosis and acquired immunodeficiency syndrome exemplify strategies for survival in the host. Indeed, both Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV-1) are successful intracellular microbes that thrive in Mɸs. Given these microbes not only co-circulate throughout the developing world but each has contributed to prevalence and mortality caused by the other, substantial insights into microbe physiology and host defenses then rest in the attempt to fully understand their influence on Mɸ polarization. This review addresses the role of Mɸ polarization in the immune response to, and pathogenesis of, Mtb and HIV.
Study of a Secure E-lottery scheme based on E-cash

The similarity of E-cash and E-lottery was taken into account to have designed a secure E-cash-lottery scheme by using zero-knowledge proof and blind signature on the basis of applications of the traditional lottery. This E-cash-lottery is characterized with anonymity, double stake resisting, forgery resisting, traceableness and off-line. For lottery players, banks, and lottery delivery to infer the identity of the winners by E-lottery is as difficult as for them to solve discrete logarithm. For lottery players to forge the E-cash or the E-cash-lottery is as difficult as for them to attack the RSA public key signature system. If there exists any repeated spending by using this E-cash- lottery, the bank can certainly determine the identity of the spender. Compared with the traditional lottery, the anonymity and privacy of the E-cash-lottery were preferable.
Effective Searching in Structured Data

Keyword search is the mechanism of choice for information discovery and retrieval due to the enormous success of Internet search engines. In fact, nearly half of Internet users perform at least one search daily. The keyword search paradigm regrettably does not extend to similar forms of content, particularly semistructured and relational data. Searching structured content is difficult because structured data challenges important assumptions of scoring models developed for unstructured text. First, a complete document may not provide the correct granularity for search results—it may be too coarse (that is, containing irrelevant information) or too fine (that is, lacking context). Second, the relationships among data must be considered, for the correct interpretation of structured data depends on understanding its relationships. Searching relational data is particularly difficult due to the data normalization process that guides the design of relational databases. Although a number of systems have been proposed to remedy this situation, none have met with considerable success. The search techniques described in this thesis apply to both semi-structured and relational data. The key contributions include an intuitive scoring model for scoring related information and a novel hybrid indexing scheme. The intuitive scoring model allows reuse of existing weighting models developed for unstructured text collections; reusing these models is critical due to the extensive testing they have already seen. Also included in the scoring model is 1) an innovative score normalization that blurs the distinction between unstructured text and information connected by relationships and 2) a factor that recalibrates the raw score produced by the weighting model so that the final score adheres to users’ expectations. The hybrid indexing scheme practically eliminates data redundancy by exploiting the full-text indexing capabilities of the underlying relational database. A small data graph stored in main memory allows efficient graph traversals to identify related information. Evaluation on two widely different datasets demonstrates the effectiveness of the techniques.
Modelling Prostate Motion for Data Fusion During Image-Guided Interventions

There is growing clinical demand for image registration techniques that allow multimodal data fusion for accurate targeting of needle biopsy and ablative prostate cancer treatments. However, during procedures where transrectal ultrasound (TRUS) guidance is used, substantial gland deformation can occur due to TRUS probe pressure. In this paper, the ability of a statistical shape/motion model, trained using finite element simulations, to predict and compensate for this source of motion is investigated. Three-dimensional ultrasound images acquired on five patient prostates, before and after TRUS-probe-induced deformation, were registered using a nonrigid, surface-based method, and the accuracy of different deformation models compared. Registration using a statistical motion model was found to outperform alternative elastic deformation methods in terms of accuracy and robustness, and required substantially fewer target surface points to achieve a successful registration. The mean final target registration error (based on anatomical landmarks) using this method was 1.8 mm. We conclude that a statistical model of prostate deformation provides an accurate, rapid and robust means of predicting prostate deformation from sparse surface data, and is therefore well-suited to a number of interventional applications where there is a need for deformation compensation.
Penile fracture: surgical repair and late effects on erectile function.

INTRODUCTION Penile fracture is described as a traumatic rupture of the tunica albuginea because of blunt injury of an erect penis. AIM To assess the etiology, treatment maneuvers, and late effects of penile fractures treated by surgical repair. METHODS Thirty-three patients diagnosed provisionally as having fractured penises. Thirty patients were managed by immediate surgical repair and three by delayed repair. MAIN OUTCOME MEASURES International Index of Erectile Function-5 for married cases and Single-question Self-report of Erectile Dysfunction questionnaires and recording complications after 2, 3, and 6 months. RESULTS The most common cause of fracture penis is self-inflicted acute bending (54.5%). The tear was visualized by ultrasound in 20/30 patients (66.7%) mostly on the right proximal third of the penis. All tears were unilateral with mean length 2.0 +/- 0.9 cm (range 0.5-4 cm). All patients who completed their follow-up after 6 months (N = 24) were able to achieve an adequate erection except two married cases who felt mild erectile dysfunction. Penile nodules were the most common postoperative complication (41.7%) after 6 months' follow-up. Patients treated with immediate or delayed repair had comparable complications. CONCLUSIONS Fracture penis is not uncommon as an emergency that must be repaired either immediately or delayed. Clinical diagnosis is more predictive than ultrasound in diagnosis and determining the site of the tear. Ultrasound may be of value in patients where there is clinical doubt.
A phenomenology of the 'placebo effect': taking meaning from the mind to the body.

Most mainstream attempts to understand the "placebo effect" invoke expectancy theory, arguing that expecting certain outcomes from a treatment or intervention can manifest those outcomes. Expectancy theory is incompatible with the phenomena of placebo responses, more appropriately named "meaning responses. " The expectancy account utilizes reflexive consciousness to connect a world of conceptual representations to mechanical physiology. An alternative account based upon Merleau-Ponty's motor intentionality argues that the body understands and is capable of responding to meanings without the need for any conceptual or linguistic content. A motor intentional framework of meaning poses dramatic implications for the interpretation of clinical trials and in the clinical practice of medicine. Most strongly, it argues that the empathic physician can facilitate the physiologic effects of treatments through skillful participation and manipulation of the meaning response.
SnowFlock: rapid virtual machine cloning for cloud computing

Virtual Machine (VM) fork is a new cloud computing abstraction that instantaneously clones a VM into multiple replicas running on different hosts. All replicas share the same initial state, matching the intuitive semantics of stateful worker creation. VM fork thus enables the straightforward creation and efficient deployment of many tasks demanding swift instantiation of stateful workers in a cloud environment, e.g. excess load handling, opportunistic job placement, or parallel computing. Lack of instantaneous stateful cloning forces users of cloud computing into ad hoc practices to manage application state and cycle provisioning. We present SnowFlock, our implementation of the VM fork abstraction. To evaluate SnowFlock, we focus on the demanding scenario of services requiring on-the-fly creation of hundreds of parallel workers in order to solve computationally-intensive queries in seconds. These services are prominent in fields such as bioinformatics, finance, and rendering. SnowFlock provides sub-second VM cloning, scales to hundreds of workers, consumes few cloud I/O resources, and has negligible runtime overhead.
Association between metabolic syndrome, radiographic knee osteoarthritis, and intensity of knee pain: results of a national survey.

CONTEXT Although osteoarthritis (OA) has been suggested as another component of metabolic syndrome (MetS), weight-independent associations between MetS and knee OA or intensity of arthritic knee pain remain unclear. OBJECTIVE The objective of the study was to evaluate the above associations and suggest possible mechanisms. DESIGN AND SETTING This was a cross-sectional study using the fifth Korean National Health and Nutrition Examination Survey (2010). PARTICIPANTS A total of 2363 adults (≥50 y of age) who had completed both laboratory examinations and an evaluation for radiographic knee OA participated in the study. MAIN OUTCOME AND MEASURES Radiographic knee OA was defined as a Kellgren/Lawrence grade of 2 or greater, and the intensity of arthritic knee pain was assessed using a self-reported numeric rating scale. MetS was diagnosed based on National Cholesterol Education Program-Adult Treatment Panel III criteria, and insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance index. RESULTS In a multivariable logistic regression analysis, MetS was associated with radiographic knee OA (adjusted odds ratio 1.49; 95% confidence interval 1.23-1.79; P < .001). This association was not changed significantly after further adjusting for homeostasis model assessment-estimated insulin resistance but became nonsignificant after adjusting for weight or body mass index. Age-, sex-, and weight (or body mass index)-adjusted mean score of knee pain was significantly higher in subjects with more components of MetS (P for trend = .010 or .035, respectively). CONCLUSIONS The association between MetS and radiographic knee OA can be largely explained by an excessive weight but not by insulin resistance, a key pathophysiology of MetS. Because accumulation of MetS components appears to be associated with a higher intensity of knee pain, independently of weight, appropriate treatment for MetS may be helpful for subjects with knee pain.
Five Years of Experimental Warming Increases the Biodiversity and Productivity of Phytoplankton

Phytoplankton are key components of aquatic ecosystems, fixing CO2 from the atmosphere through photosynthesis and supporting secondary production, yet relatively little is known about how future global warming might alter their biodiversity and associated ecosystem functioning. Here, we explore how the structure, function, and biodiversity of a planktonic metacommunity was altered after five years of experimental warming. Our outdoor mesocosm experiment was open to natural dispersal from the regional species pool, allowing us to explore the effects of experimental warming in the context of metacommunity dynamics. Warming of 4°C led to a 67% increase in the species richness of the phytoplankton, more evenly-distributed abundance, and higher rates of gross primary productivity. Warming elevated productivity indirectly, by increasing the biodiversity and biomass of the local phytoplankton communities. Warming also systematically shifted the taxonomic and functional trait composition of the phytoplankton, favoring large, colonial, inedible phytoplankton taxa, suggesting stronger top-down control, mediated by zooplankton grazing played an important role. Overall, our findings suggest that temperature can modulate species coexistence, and through such mechanisms, global warming could, in some cases, increase the species richness and productivity of phytoplankton communities.
Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy

The regulation and the dynamics of membrane trafficking events have been studied primarily in in vitro models that often do not fully reflect the functional complexity found in a living multicellular organism. Here we used intravital microscopy in the salivary glands of live rodents to investigate regulated exocytosis, a fundamental process in all of the secretory organs. We found that β-adrenergic stimulation elicits exocytosis of large secretory granules, which gradually collapse with the apical plasma membrane without any evidence of compound exocytosis, as was previously described. Furthermore, we show that the driving force required to complete the collapse of the granules is provided by the recruitment of F-actin and nonmuscle myosin II on the granule membranes that is triggered upon fusion with the plasma membrane. Our results provide information on the machinery controlling regulated secretion and show that intravital microscopy provides unique opportunities to address fundamental questions in cell biology under physiological conditions.
Quantifying the overall added value of dynamical downscaling and the contribution from different spatial scales

This study evaluates the added value in the representation of surface climate variables from an ensemble of regional climate model (RCM) simulations by comparing the relative skill of the RCM simulations and their driving data over a wide range of RCM experimental setups and climate statistics. The methodology is specifically designed to compare results across different variables and metrics, and it incorporates a rigorous approach to separate the added value occurring at different spatial scales. Results show that the RCMs' added value strongly depends on the type of driving data, the climate variable, and the region of interest but depends rather weakly on the choice of the statistical measure, the season, and the RCM physical configuration. Decomposing climate statistics according to different spatial scales shows that improvements are coming from the small scales when considering the representation of spatial patterns, but from the large‐scale contribution in the case of absolute values. Our results also show that a large part of the added value can be attained using some simple postprocessing methods.
Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals

Low serum apolipoprotein (Apo) A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL) and low-density lipoprotein (LDL). However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups). These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25) were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI), and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages) was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.
Anti-angiogenic Effects of Metformin, an AMPK Activator, on Human Umbilical Vein Endothelial Cells and on Granulation Tissue in Rat

Objective(s) Metformin is well known for activation of AMP-activated protein kinase (AMPK). AMPK activation inhibits mammalian target of rapamycin (mTOR) as a key signaling process in cell proliferation. Recent epidemiological studies demonstrate that metformin lowers the risk for several types of cancer in diabetic patients. Concerning the critical role of angiogenesis in the incidence and progression of tumors, we investigated the effect of metformin on human umbilical vein endothelial cells migration, as well as on vascular endothelial growth factor (VEGF) expressions in the cells and also on angiogenesis in air pouch model in rats. Materials and Methods A "wound" repair method was used to assess the cell migration (n=6). Real-time PCR was performed to quantify the mRNA expression of VEGF (n=5). In air pouch model, carrageenan was injected into the air pouches on the back of rats (n=6) and following an IV injection of carmine red dye granulomatous tissue was processed for the assessment of the dye content. An ordinary ANOVA with Student-Newman-Keuls post hoc test was used to compare groups. Results Metformin (orally, 50mg/kg) significantly (P<0.01) decreased angiogenesis in granulomatous tissue by 34% in pouch-bearing rats. Metformin at concentrations of 0.5-3 mM significantly (P<0.001) inhibited VEGF mRNA expression and endothelial cell migration. The inhibitory effects of metformin on the endothelial cell migration were reversed partially by compound C (P<0.01), an inhibitor of AMPK. Conclusion The present study reported that metformin inhibited endothelial cell migration and angiogenesis in vitro and in vivo, and the effect was partially AMPK dependent.