Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of gastrokine 1 in gastric cancer cells induces Fas‐mediated apoptosis

Gastrokine 1 (GKN1) is involved in the replenishment of the surface lumen epithelial cell layer, in maintaining the mucosal integrity, and could play a role in cell proliferation and differentiation. In fact, after injury of the gastric mucosa, restoration may occur very rapidly in the presence of GKN1. In contrast, if the protein is downregulated, the repair process may be hampered; however, application of GKN1 to gastrointestinal cells promoted epithelial restoration. Because GKN1 possesses some mitogenic effects on intestinal epithelial cells (IEC‐6) whereas this protein was also capable of inhibiting proliferation in gastric cancer cells (MKN28), we decided to study its involvement in apoptosis to understand the role of GKN1 in the modulation of inflammatory damage or tumorigenesis in gastric mucosa. We found by cytofluorimetry, Western blot and RT‐PCR that the overexpression of GKN1 in gastric cancer cell lines (AGS and MKN28) stimulated the expression of Fas receptor. Moreover, compared to control cells, a significant increase of apoptosis, evaluated by TUNEL, was observed when GKN1 transfected cells were treated with a monoclonal antibody (IgM) anti‐Fas. The activation of Fas expression was also observed by the overexpression of GKN1 in other cancer cell lines. Moreover, in GKN1‐overexpressing gastric cancer cells exposed to FasL, the activation of caspase‐3 was also observed by Western blot and fluorescence assays. Our data represent the first report for GKN1 as modulator of apoptotic signals and suggest that GKN1 might play an important role for tissue repair during the early stages of neoplastic transformation. J. Cell. Physiol. 226: 2571–2578, 2011. © 2010 Wiley‐Liss, Inc.
E5 oncoprotein retained in the endoplasmic reticulum/cis Golgi still induces PDGF receptor autophosphorylation but does not transform cells.

The E5 oncoprotein encoded by bovine papillomavirus type 1 is a homodimeric, hydrophobic polypeptide which is localized predominantly in Golgi membranes and which transforms several cell types apparently by inducing tyrosine phosphorylation of the platelet‐derived growth factor receptor (PDGF‐R). While the precise mechanism of receptor activation is unknown, E5 associates with several cellular proteins, including PDGF‐R and the 16K V‐ATPase protein, and induces the preferential phosphorylation of immature, Endo H‐sensitive forms of the receptor. To evaluate whether E5 accumulation in the Golgi was requisite for receptor phosphorylation and cell transformation, we sequestered the E5 protein in the endoplasmic reticulum (ER)/cis Golgi by appending the ER retention KDEL sequence to its C‐terminus. In transient assays and in cell lines, E5/KDEL protein and E5/KDEL* protein (a defective variant of KDEL), were stable and formed homodimers normally. E5/KDEL*, similar to wt E5, localized to the Golgi and was transformation‐proficient. In contrast, E5/KDEL failed to concentrate in the Golgi and was transformation‐incompetent. Despite these critical defects, however, E5/KDEL formed stable complexes with immature PDGF‐R and 16K and, even more unexpectedly, induced the phosphorylation of both mature and immature PDGF‐R on tyrosine residues to the same level as wt E5. These data demonstrate that E5 can bind and induce PDGF‐R phosphorylation in the ER/cis Golgi, but that successful mitogenic signalling (and consequent cell transformation) requires the translocation of E5/receptor complexes to distal Golgi compartments.
The p73 Tumor Suppressor Is Targeted by Pirh2 RING Finger E3 Ubiquitin Ligase for the Proteasome-dependent Degradation*

Background: The status of p73 expression is linked to the sensitivity of tumor cells to therapy, but how p73 expression is regulated remains uncertain. Results: Pirh2 E3 ubiquitin ligase promotes the proteasomal turnover of TAp73. Conclusion: Pirh2 is a novel E3 ligase of p73. Significance: Targeting Pirh2 to restore TAp73-mediated growth suppression in p53-deficient tumors may be developed as a novel anti-cancer strategy. The p73 gene, a homologue of the p53 tumor suppressor, is expressed as TA and ΔN isoforms. TAp73 has similar activity as p53 and functions as a tumor suppressor whereas ΔNp73 has both pro- and anti-survival functions. While p73 is rarely mutated in spontaneous tumors, the expression status of p73 is linked to the sensitivity of tumor cells to chemotherapy and prognosis for many types of human cancer. Thus, uncovering its regulators in tumors is of great interest. Here, we found that Pirh2, a RING finger E3 ubiquitin ligase, promotes the proteasome-dependent degradation of p73. Specifically, we showed that knockdown of Pirh2 up-regulates, whereas ectopic expression of Pirh2 down-regulates, expression of endogenous and exogenous p73. In addition, Pirh2 physically associates with and promotes TAp73 polyubiquitination both in vivo and in vitro. Moreover, we found that p73 can be degraded by both 20 S and 26 S proteasomes. Finally, we showed that Pirh2 knockdown leads to growth suppression in a TAp73-dependent manner. Taken together, our findings indicate that Pirh2 promotes the proteasomal turnover of TAp73, and thus targeting Pirh2 to restore TAp73-mediated growth suppression in p53-deficient tumors may be developed as a novel anti-cancer strategy.
Identiying Homogenous Customer Segments for Low Risk Email Marketing Experiments

Research in email marketing is divided into two broad areas spam and improving response rate. In this paper we propose a methodology which allows companies to experiment with their email campaigns to increase the campaigns’ response rate, This methodology is particularly suited for companies that are reluctant to experiment with their customer’s data fearing a drop of the response rate due to unsuccessful changes of the email campaign. The goals of this research have been achieved in two steps. Firstly, homogenous groups of customers are identified, eliminating largely any hindering heterogeneity. Secondly, customers that are not clicking and/or having a low click rate within their homogenous groups are identified.
Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain.

BACKGROUND The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists. OBJECTIVES Designing the first set of classification criteria for the classification of central sensitization pain. METHODS A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain. RESULTS It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory). LIMITATIONS Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies. CONCLUSION Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain.
Comparison of phototherapy two times and four times a week with low doses of narrow‐band ultraviolet B in Asian patients with psoriasis

Background/Aims: The optimum narrow‐band (TL‐01) ultraviolet (UV) B weekly treatment frequency for psoriasis has yet to be defined, especially in Asian patients with TL‐01. Our purpose was to compare 2× weekly and 4× weekly therapy with narrow‐band UVB at low doses for psoriasis vulgaris.
Exopolysaccharide Biosynthesis in Lactococcus lactis NIZO B40: Functional Analysis of the Glycosyltransferase Genes Involved in Synthesis of the Polysaccharide Backbone

ABSTRACT We used homologous and heterologous expression of the glycosyltransferase genes of the Lactococcus lactis NIZO B40 eps gene cluster to determine the activity and substrate specificities of the encoded enzymes and established the order of assembly of the trisaccharide backbone of the exopolysaccharide repeating unit. EpsD links glucose-1-phosphate from UDP-glucose to a lipid carrier, EpsE and EpsF link glucose from UDP-glucose to lipid-linked glucose, and EpsG links galactose from UDP-galactose to lipid-linked cellobiose. Furthermore, EpsJ appeared to be involved in EPS biosynthesis as a galactosyl phosphotransferase or an enzyme which releases the backbone oligosaccharide from the lipid carrier.
Genetic and Physiological Analysis of an Irradiated Bloomless Mutant (Epicuticular Wax Mutant) of Sorghum

An irradiation-induced bloomless mutant of sorghum [Sorghum bicolor (L.) Moench. ], KFS2021, which visually exhibits an absence of white fl uffy epicuticular wax in leaf and sheath, was characterized using a combination of genetic and physiological approaches. Study of the phenotypic segregation for the bloomless trait in F 2 and F 2:3 populations from a cross between KFS2021 and BTx623 (a cultivar with bloom showing profuse deposition of white epicuticular wax) suggests that bloomless is controlled by a single nuclear recessive gene. The bloomless parent (KFS2021) and F 2 individuals had lower frequency of guttation, leakier epidermal layer (based on percentage of chlorophyll leaching), and higher rate of seedling water loss than the BTx623 and F 2 bloom individuals. Bloomless F 2 individuals showed 3- to 6-fold higher nighttime transpiration rates relative to F 2 bloom individuals based on nighttime conductance. Correlation analysis showed signifi cant negative associations between leaf epicuticular wax load with epidermal permeability and nighttime conductance, which indicate the important role of epicuticular wax in these traits. These results suggest that epicuticular wax may enhance water use effi ciency of sorghum by regulating nighttime water loss.
The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. Methods: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. Results: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability [heritability = 58% (95% confidence interval, 52%–63%)] of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. Conclusions: Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age. Impact: Findings affect the search for genetic and epigenetic markers and frame prevention efforts. Cancer Epidemiol Biomarkers Prev; 23(11); 2303–10. ©2014 AACR.
Multifaceted Intervention to Prevent Venous Thromboembolism in Patients Hospitalized for Acute Medical Illness: A Multicenter Cluster-Randomized Trial

Background Misuse of thromboprophylaxis may increase preventable complications for hospitalized medical patients. Objectives To assess the net clinical benefit of a multifaceted intervention in emergency wards (educational lectures, posters, pocket cards, computerized clinical decision support systems and, where feasible, electronic reminders) for the prevention of venous thromboembolism. Patients/Methods Prospective cluster-randomized trial in 27 hospitals. After a pre-intervention period, centers were randomized as either intervention (n = 13) or control (n = 14). All patients over 40 years old, admitted to the emergency room, and hospitalized in a medical ward were included, totaling 1,402 (712 intervention and 690 control) and 15,351 (8,359 intervention and 6,992 control) in the pre-intervention and intervention periods, respectively. Results Symptomatic venous thromboembolism or major bleeding (primary outcome) occurred at 3 months in 3.1% and 3.2% of patients in the intervention and control groups, respectively (adjusted odds ratio: 1.02 [95% confidence interval: 0.78–1.34]). The rates of thromboembolism (1.9% vs. 1.9%), major bleedings (1.2% vs. 1.3%), and mortality (11.3% vs. 11.1%) did not differ between the groups. Between the pre-intervention and intervention periods, the proportion of patients who received prophylactic anticoagulant treatment more steeply increased in the intervention group (from 35.0% to 48.2%: +13.2%) than the control (40.7% to 44.1%: +3.4%), while the rate of adequate thromboprophylaxis remained stable in both groups (52.4% to 50.9%: -1.5%; 49.1% to 48.8%: -0.3%). Conclusions Our intervention neither improved adequate prophylaxis nor reduced the rates of clinical events. New strategies are required to improve thromboembolism prevention for hospitalized medical patients. Trial Registration ClinicalTrials.gov NCT01212393
Reverse transcriptase of human immunodeficiency virus type 1: functionality of subunits of the heterodimer in DNA synthesis

From an in vitro analysis of the DNA-synthesizing abilities of certain specifically mutated forms of the heterodimeric reverse transcriptase of human immunodeficiency virus type 1, we can conclude that in a heterodimer, the functionality of p66 is necessary while the functionality of the p51 subunit is not needed. Conversely, p51 is not able to catalyze DNA synthesis when associated with p66, and yet when the p66 protein is absent, p51 can function. These conclusions applied to DNA synthesis on heteropolymeric RNA and DNA templates.
Tumor necrosis factor triggers redistribution to a Triton X‐100‐insoluble, cytoskeletal fraction of β2 integrins, NADPH oxidase components, tyrosine phosphorylated proteins, and the protein tyrosine kinase p58fgr in human neutrophils adherent to fibrinogen

Tumor necrosis factor (TNF) triggers cell spreading, release of granule constituents, and production of toxic oxygen derivatives in human neutrophils adherent to fibrinogen. This response requires cytoskeleton reorganization and is dependent on expression of β2 integrins. We analyzed distribution of distinct proteins in Triton X‐100–soluble and insoluble fractions in neutrophils adherent to fibrinogen. We found that stimulation of adherent neutrophils with TNF causes the redistribution to a Triton‐insoluble fraction of α‐actinin, β2 integrins, and the four components whose assembly constitutes an active NADPH oxidase: the gp91‐phox, p22‐phox, p47‐phox, and p67‐phox proteins. Redistribution of these different proteins to a Triton‐insoluble fraction took relatively long times and was maximal after about 30 min of stimulation with TNF. Prevention of actin polymerization with cytochalasin B hampered the TNF‐induced redistribution of these proteins from a Triton‐soluble to an insoluble fraction. In addition, tyrosine phosphorylated proteins and the protein tyrosine kinase p58fgr were recovered in this Triton‐insoluble fraction. These findings show that stimulated, β2 integrin–dependent adhesion of neutrophils to fibrinogen is accompanied by redistribution to cytoskeletal structures of (1) β2 integrins, that is, neutrophil receptors for fibrinogen; (2) proteins involved in neutrophil effector functions, that is, components of NADPH oxidase; and (3) tyrosine phosphorylated proteins and the protein tyrosine kinase p58fgr, molecules that are potentially involved in the formation of a submembranous signaling complex.
Auditory Impairment in Children with Cerebral Palsy

Cerebral palsy refers to a group of conditions that affect control of movement and posture.The aim of our study was to detect early changes in audiologic function in children with cerebral palsy. Data resulting from audiometry, tympanometry and auditory brain stem response of thirty children with cerebral palsy were collected and analyzed. Abnormal tympanometry in the form of secretory otitis media and Eustachian tube dysfunction was present in 52% of spastic quadriplegic patients, while sensorineural hearing loss was present in 40% of our patients. Early audiological assessment in children with cerebral palsy, allows early aural habilitation which enable better development of hearing and speech in these children and hence, auditory brain stem testing should be incorporated into the diagnostic plan of all children with spastic cerebral palsy.
Ten Years of Experience with First-Trimester Screening for Fetal Aneuploidy Employing Biochemistry from Gestational Weeks 6+0 to 13+6

Objectives: To validate the performance of first-trimester screening for fetal aneuploidy employing blood samples drawn in gestational weeks 6-13. Methods: Prospective combined first-trimester screening for fetal aneuploidy in Denmark was validated in two large datasets: (1) a dataset from the Central Denmark Region including 147,768 pregnancies from October 2003 to October 2013, and (2) a national dataset including 220,739 pregnancies from January 2008 to August 2011. Results: For trisomy 21, the weekly median multiple of the median (MoM) increased from 0.37 in week 6 to 0.70 in week 13 (pregnancy-associated plasma protein-A), and from 0.99 in week 6 to 2.68 in week 13 (free βhCG). The overall detection rate (DR) for fetal trisomy 21 was 91.2%. Employing blood samples from gestational week 9, the DR was 97% (p = 0.05). For fetal trisomy 18, trisomy 13 and triploidy, the overall DRs after first-trimester screening were 79.5, 86 and 85%. In the national dataset, the overall DR for trisomy 21 was 86.3% ranging from 89 (weeks 9 and 10) to 80% (weeks 12 and 13). Conclusion: The results from both datasets show that blood sampling in gestational weeks 9-10 is a robust and high-performance strategy, which can be applied for routine first-trimester screening in clinical practice.
The dress room: responsive spaces and embodied interaction

What does it entail to be embraced by a space that responds to your actions? What kind of relations can we create between the active body and the active space? What qualities does the responsivity have for creating certain experiences of a space? Through the Dress Room, I begin to explore the qualities of responsive spaces and embodied interaction. The Dress Room is a white cube that responds to the body's movements over the floor. The walls move, the room collapses or expands. I rely on a dancer to open up this experience. The outcome suggests that interacting with responsive environments can help create a sense of intimacy as well as motivate our motions within the space.
Title An Investigation into Information Navigation via DiverseKeyword-based Facets

In the age of information overload, it is necessary to provide effective information navigation tools that operate over unstructured textual data. Current state-of-the-art methods are limited in terms of providing effective exploration capabilities for various information seeking tasks, especially those arising in domains such as online journalism. Here we argue for improvements in faceted search systems, via new strategies for identifying keyword-based facets. Our proposed technique utilises a PageRank model operating over the graph of terms appearing in documents, while also employing novel methods for biasing significant terms and named entities. In addition, we consider the notion of diversity within extracted keywords in an effort to maximize coverage over a range of topics. We perform experimental evaluations over issues relevant to the Irish General Elections 2016, demonstrating the superior performance of our proposed technique.
Materiales fotocatalíticos y sus aplicaciones en construcción

En el documento a continuacion expuesto se presentan algunos conceptos basicos relativos a la contaminacion atmosferica. Aunque, posteriormente se enfocara desde un punto de vista de la reduccion de la contaminacion a traves de los materiales de construccion. Para adentrarnos en dicho tema, es interesante conocer de antemano cuales son los principales contaminantes, sus fuentes emisoras, sus caracteristicas fisicoquimicas, los metodos analiticos que utilizan las estaciones de control de la contaminacion atmosferica, los limites establecidos por la legislacion vigente y las recomendaciones de la Organizacion Mundial de la Salud respecto a los niveles de emision. Veremos que el interes de reducir los contaminantes mediante materiales de construccion con efectos descontaminantes se debe centrar sobre todo en ambientes urbanos donde las altas concentraciones de los compuestos contaminantes se hacen mas latentes (debido a las emisiones de los vehiculos y las industrias) y donde el efecto de estos materiales sera mucho mas util. Veremos cuales son los compuestos contaminantes mas perjudiciales segun el Estudio Multicentrico Espanol de Contaminacion Atmosferica y Mortalidad (EMECAM). Asi como lo que dicta el nuevo conjunto de directivas de la Union Europea y las recomendaciones ultimas de la Organizacion Mundial de la Salud acerca de la contaminacion.Asi pues, se hace necesario un ambiente mas limpio y una mayor calidad de vida. Aqui es donde entra en juego la fotoquimica como proceso ecologico que utiliza la luz solar para crear reacciones que destruyen los compuestos contaminantes. Esto lleva a pensar concretamente en la fotocatalisis aplicada a los materiales de construccion como una solucion interesante para reducir la contaminacion en las ciudades. Por ello en la ultima parte se recopilan los materiales de construccion y los elementos constructivos que contienen nano-compuestos con caracteristicas fotocataliticas mas usuales en el mercado. En todos estos casos, los materiales tendran la capacidad de reducir el nivel de sustancias contaminantes organicas e inorganicas presentes en el aire que los rodea ademas de contar con propiedades autolimpiantes, lo que conlleva un menor coste en mantenimiento. El documento tambien recoge grandes obras de interes donde se han aplicado este tipo de materiales y en algunos casos los resultados de descontaminacion ambiental que dichos materiales han producido. Y finalmente se ha elaborado un caso practico de estudio que pretende orientar sobre los sobrecostes de la utilizacion de estos materiales fotocataliticos en vez de los tradicionales en la parte de la envolvente del edificio y ademas ver los rangos de descomposicion de los gases NOx (los compuestos mas daninos para nuestra salud) que producen dichos materiales.