Miracle-dz/UniFAR-FTUs huggingface dataset:
A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2‐associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97‐147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16‐bp insertion and the variant allele for the Arg72Pro (No Ins‐72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins‐72Pro haplotype (OR: 2.69; 95% CI: 1.15–6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins‐72Pro haplotype. Hum Mutat 27(3), 242–248, 2006. © 2006 Wiley‐Liss, Inc.
PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor

Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.
Diastolic abnormalities in patients with hypertrophic cardiomyopathy: relation to magnitude of left ventricular hypertrophy.

To investigate the relationship between diastolic abnormalities and left ventricular hypertrophy, 52 patients with hypertrophic cardiomyopathy (HCM) and 22 normal subjects were studied with digitized M mode echocardiography and two-dimensional echocardiography. Echocardiographic indexes of diastolic function were compared in patients with different extent of left ventricular hypertrophy. Time interval from minimum left ventricular internal dimension to mitral valve opening and time to peak rate of increase in left ventricular internal dimension were significantly prolonged (80 +/- 31 and 100 +/- 37 msec, respectively) in patients with HCM and the most extensive left ventricular hypertrophy compared with those in patients with mild left ventricular hypertrophy (59 +/- 25 and 74 +/- 34 msec, respectively; p less than .01). Furthermore, peak rate of posterior wall diastolic excursion was significantly reduced in those patients with HCM and posterior wall hypertrophy (8.3 +/- 4.0 cm/sec) compared with that in patients with HCM but normal posterior wall thickness (11.2 +/- 3.4 cm/sec; p less than .002). However, abnormal M mode echocardiographic indexes of diastolic function were also identified in a substantial proportion of patients (i.e., 73%) with HCM and only mild left ventricular hypertrophy. In these patients, time interval from minimum left ventricular internal dimension to mitral valve opening (59 +/- 25 msec), peak rate (12 +/- 4 cm/sec), and time to peak rate of increase in left ventricular internal dimension (74 +/- 34 msec) were significantly different from normal (25 +/- 12 msec, 21 +/- 3 cm/sec, and 49 +/- 12 msec, respectively; p less than .01). (ABSTRACT TRUNCATED AT 250 WORDS)
What addiction spells for the female psyche: a five-factor model personality profile comparison between alcohol dependence and multiple substance dependence in females

Background: In spite of decades of research regarding substance dependence, till recently its manifestations were focused more so in males. The aim of the present study thus, was to explore and compare between the personality dimensions of females with addiction. Methods: For this purpose, 20 female patients having alcohol dependence and 20 female patients having multiple substance dependence were taken along with 20 matched female individuals for a healthy comparative group (HCG). All the groups were administered the sociodemographic clinical datasheet and NEO-Five Factor Inventory. Statistical analysis included Kruskal Wallis H test to find out the difference between the groups with substance dependence and HCG, followed by Mann Whitney U test as post hoc to find out the difference. Results: The results indicated that the groups with substance dependence differed significantly from HCG with respect to neuroticism, agreeableness, and conscientiousness. Furthermore, results showed that there was no significant difference between the groups on the other two factors of extraversion and openness to experience. Post hoc analysis revealed no significant difference amongst the group with alcohol dependence and the group with multiple substance dependence on these domains even though both differed from HCG. Conclusion: This implies that female patients with alcohol dependence and multiple substance dependence had a higher level of negative affect, lower tendency to agree and exhibit less conscientiousness, that is be self-disciplined or well organised and in adhering to rules which may be related to their substance dependence.
Characterization of Odorant Receptors from a Non-ditrysian Moth, Eriocrania semipurpurella Sheds Light on the Origin of Sex Pheromone Receptors in Lepidoptera.

Pheromone receptors (PRs) are essential in moths to detect sex pheromones for mate ﬁnding. However, it remains unknown from which ancestral proteins these specialized receptors arose. The oldest lineages of moths, so-called non-ditrysian moths, use short-chain pheromone components, secondary alcohols, or ketones, so called Type 0 pheromones that are similar to many common plant volatiles. It is, therefore, possible that receptors for these ancestral pheromones evolved from receptors detecting plant volatiles. Hence, we identiﬁed the odorant receptors (ORs) from a non-ditrysian moth, Eriocrania semipurpurella (Eriocraniidae, Lepidoptera), and performed functional characterization of ORs using HEK293 cells. We report the ﬁrst receptors that respond to Type 0 pheromone compounds; EsemOR3 displayed highest sensitivity toward (2 S , 6 Z )-6-nonen-2-ol, whereas EsemOR5 was most sensitive to the behavioral antagonist ( Z )-6-nonen-2-one. These receptors also respond to plant volatiles of similar chemical structures, but with lower sensitivity. Phylogenetically, EsemOR3 and EsemOR5 group with a plant volatile-responding receptor from the tortricid moth Epiphyas postvittana (EposOR3), which together reside outside the previously deﬁned lepidopteran PR clade that contains the PRs from more derived lepidopteran families. In addition, one receptor (EsemOR1) that falls at the base of the lepidopteran PR clade, responded speciﬁcally to b -caryophyllene and not to any other additional plant or pheromone compounds. Our results suggest that PRs for Type 0 pheromones have evolved from ORs that detect structurally-related plant volatiles. They are unrelated to PRs detecting pheromones in more derived Lepidoptera, which, in turn, also independently may have evolved a novel function from ORs detecting plant volatiles.
Restructuring Counterparty Credit Risk

We introduce an innovative theoretical framework for the valuation and replication of derivative transactions between defaultable entities based on the principle of arbitrage freedom. Our framework extends the traditional formulations based on credit and debit valuation adjustments (CVA and DVA). Depending on how the default contingency is accounted for, we list a total of ten different structuring styles. These include bi-partite structures between a bank and a counterparty, tri-partite structures with one margin lender in addition, quadri-partite structures with two margin lenders and, most importantly, configurations where all derivative transactions are cleared through a central counterparty clearing house (CCP). We compare the various structuring styles under a number of criteria including consistency from an accounting standpoint, counterparty risk hedgeability, numerical complexity, transaction portability upon default, induced behavior and macro-economic impact of the implied wealth allocation.
Googling the news Opportunities and challenges in studying news events through Google Search

: Search engines provide a window into the changing association between websites and keywords across cultures and countries and over time. As such, they offer journalism and news researchers an opportunity to study how search engines, in this case Google, mediate news events and stories online. However, search results are not straightforward to study. Since search results are made in the act of searching and will have to be retrieved from Google Search in real-time, there is a range of different ontological and methodological issues related to this data source. This paper addresses these issues by discussing how factors in the search algorithm can be used proactively to study variations across searchers and in time. The paper identifies various endogenous and exogenous factors in the search algorithm one has to pay attention to and discusses ways to archive search results accordingly. Through a small case study, ways to work with the influence of endogenous factors (keywords, language settings, geo-location, web history and clicking behaviour) and mitigate the effects of the exogenous factors (experimentation and randomization) are suggested. Then, a new approach to studying search results is put forward, which builds on purposeful sampling of real-world participants or constructed research profiles. Finally, perspectives for news and journalism scholars in studying algorithmically generated content in a broader context are offered.
Domain of attraction analysis for continuous-time Takagi-Sugeno fuzzy systems: An LMI approach

This paper proposes a strategy to estimate invariant subsets of the domain of attraction (DA) for continuous-time Takagi-Sugeno (T-S) fuzzy systems. The result is based on the so-called fuzzy Lyapunov function, which is used to characterize the subsets of the DA as sublevel sets of the Lyapunov function. The key idea relies on casting the Lyapunov inequality that includes the time-derivative of the membership functions into linear matrix inequalities (LMIs) by considering a bound on the nonlinear function dependent quadratically on the time-derivative of the membership functions. Finally, an example is given to demonstrate the effectiveness of the proposed approach.
Proportional differentiated services: delay differentiation and packet scheduling

Internet applications and users have very diverse service expectations, making the current same-service-to-all model inadequate and limiting. In the relative differentiated services approach, the network traffic is grouped in a small number of service classes which are ordered based on their packet forwarding quality, in terms of per-hop metrics for the queueing delays and packet losses. The users and applications, in this context, can adaptivelychoose the class that best meets their quality and pricing constraints, based on the assurance that higher classes will be better, or at least no worse, than lower classes. In this work, we propose the proportional differentiation model as a way to refine and quantify this basic premise of relative differentiated services. The proportional differentiation model aims to provide the network operator with the 'tuning knobs' for adjusting the quality spacing between classes, independent of the class loads; this cannot be achieved with other relative differentiation models, such as strict prioritization or capacity differentiation. We apply the proportional model on queueing-delay differentiation only, leaving the problem of coupled delay and loss differentiation for future work. We discuss the dynamics of the proportional delay differentiation model and state the conditions under which it is feasible. Then, we identify and evaluate (using simulations) two packet schedulers that approximate the proportional differentiation model in heavy-load conditions, even in short timescales. Finally, we demonstrate that such per-hop and class-based mechanisms can provide consistent end-to-end differentiation to individual flows from different classes, independently of the network path and flow characteristics.
Wilt-Associations of inflammatory and reproductive tract disorders postpartum with pregnancy and early pregnancy loss in dairy cows

Our objective was to describe associations of post-partum health with pregnancy and pregnancy loss (P-LOSS) from d 19 to 40 after first postpartum artificial insemination (AI) in lactating Holstein cows. In 2 commercial dairy herds in Ontario, Canada, 468 Holstein cows were enrolled 21 ± 3 d before expected parturition when body condition score (BCS) and lameness were assessed. Serum total Ca, haptoglobin (Hp), and nonesterified fatty acids (NEFA) were measured at 2 and 6 ± 2 d in milk (DIM). Blood β-hydroxybutyrate (BHB) measurement and metritis detection were done at 4, 8, 11, and 15 ± 2 DIM. Cows were examined for endometritis (ENDO; ≥11.5% polymorphonuclear cells in endometrial cytology) and purulent vaginal discharge (PVD) at 35 ± 3 DIM. Lameness was assessed again at 21 and 49 ± 3 DIM and BCS at 63 ± 3 DIM. First postpartum AI occurred primarily (86%) based on detection of estrus by activity monitors, on average (± standard deviation) at 65 ± 9 DIM, and the remaining cows received timed AI at 86 ± 18 DIM. Serum progesterone (P4) was measured on d 8 and 12 after AI, and pregnancy at first AI (P/AI) was estimated by the expression of ISG15 in peripheral blood leukocytes at d 19 after AI and by pregnancy-associated glycoprotein in serum at d 29, 33, and 40 after AI. Each metabolite (Ca, Hp, NEFA, and BHB) was categorized above or below a cut-point identified with receiver operating characteristic curve analysis associated with P/AI confirmed by ultrasound at d 33 from a larger data set. Data were analyzed using multivariable mixed logistic regression models, accounting for parity, health variables, covariates (season at calving and at AI, milk yield at first Dairy Herd Improvement Association test [categorized into terciles], AI method, and DIM), and herd. The proportions of cows classified pregnant at d 19, 29, 33, and 40 after AI were 64%, 54%, 50%, and 45%, respectively. At d 19 after AI, P/AI was less likely in cows diagnosed with ENDO (52% vs. 69%) or PVD (54% vs. 67%). At d 29, P/AI was less likely in cows with Hp ≥1.54 g/L at 2 DIM (38% vs. 55%) or PVD (35% vs. 56%). Both metritis and ENDO were associated with decreased P/AI at d 40 after AI. Cows diagnosed with metritis had greater risk of P-LOSS from d 19 to 29 (43% vs. 22%) or from d 33 to 40 (37% vs. 7%) than cows without metritis. From d 29 to 33, the risk of P-LOSS was greater in cows with NEFA ≥0.73 m M at 2 DIM (13% vs. 5%) or BCS ≤2.75 at 63 DIM (14% vs. 5%). The concentration of P4 on d 8 after AI was positively associated with P/AI at d 29, 33, and 40, and negatively associated with P-LOSS from d 19 to 29. Postpartum health disorders, particularly reproductive tract disease, can have detrimental effects on early pregnancy establishment and on pregnancy maintenance from d 19 to 40 after AI.
Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes

Because of the importance of neural recognition molecules expressed by glial cells to mediate interactions with neurons, growth factors and cytokines known to be functional during morphogenesis and in diseases of the nervous system were studied for their effects on recognition molecule expression by cultured immature and mature astrocytes from several brain regions. In cultures of immature astrocytes, transforming growth factors-beta 1 (TGF-beta 1) and -beta 2 (TGF-beta 2) and nerve growth factor (NGF) increased expression of the neural adhesion molecule L1, leading to a glia-mediated L1-specific increase in neurite outgrowth of dorsal root ganglion neurons on the astrocyte substrate. L1 expression induced by TGF-beta was inhibited by addition of antibodies to NGF, suggesting that TGF-beta influences L1 expression by modulating production of NGF by astrocytes. TGF-beta 1 and -beta 2 decreased expression of N-CAM by immature astrocytes. Since N-CAM expression was not affected by NGF and antibodies to NGF did not abolish the TGF-beta-induced decrease in N-CAM expression, NGF did not appear to be the mediator for regulating expression of N-CAM. Expression of the adhesion molecule on glia (AMOG) was not affected by any factor. NGF and TGF-beta 2 in latent form, but not TGF-beta 1 were found in the culture supernatants. Addition of interferon-gamma (IFN- gamma), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), platelet- derived growth factor (PDGF), or basic fibroblast growth factor (bFGF) to the cultures did not change recognition molecule expression. REcognition molecule expression by mature astrocytes was not found to be modified by any of the factors tested. In view of the observation that levels of L1 and N-CAM expression correlated with the presence of TGF-beta 2 and NGF in the culture supernatants of immature astrocytes, an autocrine regulatory mechanism for recognition molecule expression by these cells is suggested to play a crucial role in regulation of neuron-glia interactions.
Morphine-Induced Changes in δ Opioid Receptor Trafficking Are Linked to Somatosensory Processing in the Rat Spinal Cord

An in vivo fluorescent deltorphin (Fluo-DLT) internalization assay was used to assess the distribution and regulation of pharmacologically available δ opioid receptors (δORs) in the rat lumbar (L4-5) spinal cord. Under basal conditions, intrathecal injection of Fluo-DLT resulted in the labeling of numerous δOR-internalizing neurons throughout dorsal and ventral horns. The distribution and number of Fluo-DLT-labeled perikaryal profiles were consistent with that of δOR-expressing neurons, as revealed by in situ hybridization and immunohistochemistry, suggesting that a large proportion of these cells was responsive to intrathecally administered δOR agonists. Pretreatment of rats with morphine for 48 hr resulted in a selective increase in Fluo-DLT-labeled perikaryal profiles within the dorsal horn. These changes were not accompanied by corresponding augmentations in either δOR mRNA or 125I-deltorphin-II binding levels, suggesting that they were attributable to higher densities of cell surface δOR available for internalization rather than to enhanced production of the receptor. Unilateral dorsal rhizotomy also resulted in increased Fluo-DLT internalization in the ipsilateral dorsal horn when compared with the side contralateral to the deafferentation or to non-deafferented controls, suggesting that δOR trafficking in dorsal horn neurons may be regulated by afferent inputs. Furthermore, morphine treatment no longer increased Fluo-DLT internalization on either side of the spinal cord after unilateral dorsal rhizotomy, indicating that μOR-induced changes in the cell surface availability of δOR depend on the integrity of primary afferent inputs. Together, these results suggest that regulation of δOR responsiveness through μOR activation in this region is linked to somatosensory information processing.
Redefining the Organizational Resilience Construct using a Frame Based Methodology: A New Perspective from the Ecology Based Approach

While scholars have been elaborating on the nature and scope of the resilience for some time, the contemporary era of monumental disruptions have elevated this topic to the top of scholarly and practical attention. Yet, there is much confusion and ambiguity about how it should be defined and measured. In addition, definitions of resilience appear to vary greatly across disciplines. Given these shortcomings, this study first presents a framing of resilience definition using categorization of attributes under process, structure and strategic move/action, emanating from cross-disciplinary foundation. Second, the study offers conjectures and propositions for multinational enterprises (MNEs) under process, structure and strategic move/action drawing ideas from social, mechanical, and ecological literature regarding this construct. Third, we present a new frame-based methodological approach in presenting the attributes and subordinate concepts of resilience.