Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediagnostic telomere length and risk of B‐cell lymphoma—Results from the EPIC cohort study

Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B‐cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case–control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p = 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2–4, respectively, p‐trend = 0.001], diffuse large B‐cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2–4, respectively, p‐trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2–4, respectively, p‐trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.
Sociodemographic and personal factors related to depressive symptomatology in the Mexican population aged 12 to 65.

OBJECTIVE To describe the prevalence of depressive symptoms in the Mexican population, aged 12 to 65 years, by identifying the main related socio-demographic and personal factors. METHODS Data are drawn from the National Survey on Addictions 2008 (ENA 2008), a random, probabilistic, multistage study. A randomly selected sub-sample of 22,962 persons answered the section on depressive symptomatology, measured with the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS The total prevalence for depressive symptomatology was 5.1%; the prevalence was 7.5% for women and 2.5% for men. For women, more evidence of depressive symptoms was seen in the central region, whereas for men, symptoms were homogeneous across the country. Factors related to the presence of depressive symptoms include being divorced (in women) or widowed (in men), having lower educational attainment, perceiving one's place of residence as unsafe, displaying alcohol abuse or dependence, being a regular drug consumer (in men) and having been sexually abused (males and females). CONCLUSIONS The regional distribution of depressive symptomatology in women indicates the need for region-specific prevention programs that take into account the different social problems that affect women's emotional well-being. More research is also needed to support the early identification and intervention of men suffering from depression.
Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic Neurovascular Coupling

According to the current model of neurovascular coupling, blood flow is controlled regionally through phasic changes in the activity of neurons and astrocytes that signal to alter arteriole diameter. Absent in this model, however, is how brain blood flow is tonically regulated independent of regional changes in activity. This is important because a large fraction of brain blood flow is required to maintain basal metabolic needs. Using two-photon fluorescence imaging combined with patch-clamp in acute rat brain slices of sensory-motor cortex, we demonstrate that reducing resting Ca2+ in astrocytes with intracellular BAPTA causes vasoconstriction in adjacent arterioles. BAPTA-induced vasoconstriction was eliminated by a general COX blocker and the effect is mimicked by a COX-1, but not COX-2, antagonist, suggesting that astrocytes provide tonic, steady-state vasodilation by releasing prostaglandin messengers. Tonic vasodilation was insensitive to TTX, as well as a variety of synaptic and extrasynaptic receptor antagonists, indicating that the phenomenon operates largely independent of neural activity. Using in vivo two-photon fluorescence imaging of the barrel cortex in fully awake mice, we reveal that acute COX-1 inhibition reduces resting arteriole diameter but fails to affect vasodilation in response to vibrissae stimulation. Our findings demonstrate that astrocytes provide tonic regulation of arterioles using resting intracellular Ca2+ in a manner that is independent of phasic, neuronal-evoked vasodilation. SIGNIFICANCE STATEMENT The brain requires both phasic and tonic regulation of its blood supply to service energy needs over various temporal windows. While many mechanisms have been described for phasic blood flow regulation, how the brain accomplishes tonic control is largely unknown. Here we describe a way in which astrocytes contribute to the management of basal brain blood flow by providing steady-state vasodilation to arterioles via resting astrocyte Ca2+ and the continuous release of prostaglandin messengers. This phenomenon may be important for understanding the declines in basal brain blood flow that occur in aging and dementia, as well as for the interpretation of fMRI data.
Production of transgenic pigs using a pGFAP-CreERT2/EGFPLoxP inducible system for central nervous system disease models

Transgenic (TG) pigs are important in biomedical research and are used in disease modeling, pharmaceutical toxicity testing, and regenerative medicine. In this study, we constructed two vector systems by using the promoter of the pig glial fibrillary acidic protein (pGFAP) gene, which is an astrocyte cell marker. We established donor TG fibroblasts with pGFAP-CreERT2/LCMV-EGFPLoxP and evaluated the effect of the transgenes on TG-somatic cell nuclear transfer (SCNT) embryo development. Cleavage rates were not significantly different between control and transgene-donor groups. Embryo transfer was performed thrice just before ovulation of the surrogate sows. One sow delivered 5 TG piglets at 115 days after pregnancy. Polymerase chain reaction (PCR) analysis with genomic DNA isolated from skin tissues of TG pigs revealed that all 5 TG pigs had the transgenes. EGFP expression in all organs tested was confirmed by immunofluorescence staining and PCR. Real-time PCR analysis showed that pGFAP promoter-driven Cre fused to the mutated human ligand-binding domain of the estrogen receptor (CreERT2) mRNA was highly expressed in the cerebrum. Semi-nested PCR analysis revealed that CreERT2-mediated recombination was induced in cerebrum and cerebellum but not in skin. Thus, we successfully generated a TG pig with a 4-hydroxytamoxifen (TM)-inducible pGFAP-CreERT2/EGFPLoxP recombination system via SCNT.
Glucose Measurement in the Operating Room: More Complicated than It Seems

Abnormalities of blood glucose are common in patients undergoing surgery, and in recent years there has been considerable interest in tight control of glucose in the perioperative period. Implementation of any regime of close glycemic control requires more frequent measurement of blood glucose, a function for which small, inexpensive, and rapidly responding point-of-care devices might seem highly suitable. However, what is not well understood by many anesthesiologists and other staff caring for patients in the perioperative period is the lack of accuracy of home glucose meters that were designed for self-monitoring of blood glucose by patients. These devices have been remarketed to hospitals without appropriate additional testing and without an appropriate regulatory framework. Clinicians who are accustomed to the high level of accuracy of glucose measurement by a central laboratory device or by an automated blood gas analyzer may be unaware of the potential for harmful clinical errors that are caused by the inaccuracy exhibited by many self-monitoring of blood glucose devices, especially in the hypoglycemic range. Knowledge of the limitations of these meters is essential for the perioperative physician to minimize the possibility of a harmful measurement error. In this article, we will highlight these areas of interest and review the indications, technology, accuracy, and regulation of glucose measurement devices used in the perioperative setting.
ICP-AES Determination of Trace Rare Earth Elements in Environmental and Food Samples by On-line Separation and Preconcentration with Acetylacetone-modified Silica Gel Using Microcolumn

A novel method of online microcolumn separation and preconcentration coupled to inductively coupled plasma atomic emission spectrometry (ICP-AES) with the use of acetylacetone-modified silica gel as packing material was developed for the determination of trace rare earth elements (REEs) in environmental and food samples. The main parameters affecting online separation/preconcentration, including pH, sample flow rate, sample volume, elution and interfering ions, have been investigated in detail. Under the optimized operating conditions, the adsorption capacity values for Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu were 25.65, 23.23, 24.01, 19.40, 22.89, 23.77, 24.40, 23.96, 25.58, 25.15, 24.86, 22.75, 16.05, 24.13, 26.51 and 27.93 mg g^–1, respectively. Detection limits (3 σ ) based on three times standard deviations of the blanks by 8 replicates were in the range from 48 pg mL^–1 for Lu to 1003 pg mL^–1 for Sm. With 90 s preconcentration time and 10 s elution time, the enrichment factor was 10 and the sample frequency was 28 h^–1. The precisions (RSDs) obtained by determination of a 250 ng mL^–1 ( n = 8) REEs standard solution were in the range from 1.7% for Y to 4.4% for Sm. The proposed method was successfully applied to the determination of trace REEs in pig liver, agaric and mushroom. To validate the proposed method, we analyzed three certified reference materials (GBW07401 soil, GBW07301a sediment, and GBW07605 tea leaves). The determined values were in a good agreement with the certified values. The method is rapid, selective, sensitive and applicable to the determination of trace REEs in biological and environmental samples with complicated matrix effects.
Learning robotic soccer controllers with the Q-Batch update-rule

Robotic soccer provides a rich environment for the development of Reinforcement Learning controllers. The competitive environment imposes strong requirements on performance of the developed controllers. RL offers a valuable alternative for the development of efficient controllers while avoiding the hassle of parameter tuning a hand coded policy. This paper presents the application of a recently proposed Batch RL update-rule to learn robotic soccer controllers in the context of the RoboCup Middle Size League. The Q-Batch update-rule exploits the episodic structure of the data collection phase of Batch RL to efficiently evaluate and improve the learned policy. Three different learning tasks, with increasing difficulty, were developed and applied on a simulated environment and later on the physical robot. The performance of the learned controllers is mostly compared to hand-tuned controllers while some comparisons with other RL methods were performed. Results show that the proposed approach is able to learn the tasks in a reduced amount of time, even outperforming existing hand-coded solutions.
Mixture of Poisson distributions to model discrete stock price changes.

MIXTURE OF POISSON DISTRIBUTIONS TO MODEL DISCRETE STOCK PRICE CHANGES Rasitha Rangani Jayasekare Kodippuli Thanthillage Dona July 10, 2013 An application of a mixture of Poisson distributions is proposed to model the discrete changes in stock price based on the minimum price movement known as ‘tick-size’. The parameters are estimated using the Expectation-Maximization (EM) algorithm with a constant mixing probability as well as mixing probabilities which depend on order size. The model is evaluated using simulations and real data. Both the simulated and real data show reasonable estimates. Several adjustments are made to the model implementation to improve the efficiency with user written codes for the Newton Raphson algorithm and also implementing one of the most recent versions of the EM algorithm (PEM). Both the improvements show an exponentially increasing efficiency to the implementation. Further a Clustered Signed model is proposed to use summarized data to reduce the amount of data to be used in the model implementation using the discrete order sizes and the signs of the discrete stock price changes. The clustered model provided a significant time efficiency. A parametric bootstrap procedure is also considered to assess the significance of the order size on the mixing probabilities. The results show that the use of a variable mixture probability, which depends on the order size, is more appropriate for the model. The methods are illustrated with data from simulations and real data from Federal Express.
Evolution of immune chemoreceptors into sensors of the outside world

Significance Immune formyl peptide receptors (Fprs) evolved in rodents from expression in immune cells to be transcribed in olfactory sensory neurons. Explaining the initial neuronal acquisition, we found that an Fpr coding exon landed in front of a vomeronasal receptor promoter, hijacking its expression pattern. This type of gene shuffling occurred twice in the mouse lineage, many million years apart, leading to the exclusive expression of Fprs in the two main populations of vomeronasal sensory neurons. Finally, we demonstrate that the immune expression of one of the mouse vomeronasal Fprs can be restored via the production of an intergenic transcript. Thus, we provide the complete history of genomic events that led to a model case of evolutionary neofunctionalization in a mammal. Changes in gene expression patterns represent an essential source of evolutionary innovation. A striking case of neofunctionalization is the acquisition of neuronal specificity by immune formyl peptide receptors (Fprs). In mammals, Fprs are expressed by immune cells, where they detect pathogenic and inflammatory chemical cues. In rodents, these receptors are also expressed by sensory neurons of the vomeronasal organ, an olfactory structure mediating innate avoidance behaviors. Here we show that two gene shuffling events led to two independent acquisitions of neuronal specificity by Fprs. The first event targeted the promoter of a V1R receptor gene. This was followed some 30 million years later by a second genomic accident targeting the promoter of a V2R gene. Finally, we show that expression of a vomeronasal Fpr can reverse back to the immune system under inflammatory conditions via the production of an intergenic transcript linking neuronal and immune Fpr genes. Thus, three hijackings of regulatory elements are sufficient to explain all aspects of the complex expression patterns acquired by a receptor family that switched from sensing pathogens inside the organism to sensing the outside world through the nose.
Simultaneous measurement of thrombin generation and fibrin formation in whole blood under flow conditions

Summary Assays based on the formation of thrombin and fibrin are frequently used, and results are considered exchangeable in research/clinical settings. However, thrombin generation and fibrin formation do not always go hand in hand and flow profoundly influences thrombus formation. We describe the technical/clinical evaluation of an assay to simultaneously measure thrombin generation and fibrin formation under conditions of flow. Introduction of a fluorometer into a ‘cone and base principle’-based rheometer allowed the measurement of thrombin generation (using a thrombin-sensitive substrate) and fibrin formation (changes in viscosity), while applying a linear shear flow. Increasing shear rates inversely related with thrombin generation and fibrin formation. Increasing fibrinogen concentrations in defibrinated plasma resulted in increased thrombin generation and fibrin formation. In pre-operative samples of 70 patients undergoing cardiothoracic surgery, fibrin formation and thrombin generation parameters correlated with fibrinogen content, rotational thromboelastometry (ROTEM) and whole blood Calibrated Automated Thrombinography (CAT) parameters, respectively. Upon dividing patients into two groups based on the median clot strength, a significant difference in perioperative/total blood loss was established. In conclusion, we clinically evaluated a method capable of simultaneously measuring thrombin generation and fibrin formation in plasma/whole blood under continuous flow, rendering our method one step closer to physiology. Importantly, our test proved to be indicative for the amount of blood loss during/after cardiothoracic surgery.
Altitude and endurance training

The benefits of living and training at altitude (HiHi) for an improved altitude performance of athletes are clear, but controlled studies for an improved sea-level performance are controversial. The reasons for not having a positive effect of HiHi include: (1) the acclimatization effect may have been insufficient for elite athletes to stimulate an increase in red cell mass/haemoglobin mass because of too low an altitude (<2000-2200 m) and/or too short an altitude training period (<3-4 weeks); (2) the training effect at altitude may have been compromised due to insufficient training stimuli for enhancing the function of the neuromuscular and cardiovascular systems; and (3) enhanced stress with possible overtraining symptoms and an increased frequency of infections. Moreover, the effects of hypoxia in the brain may influence both training intensity and physiological responses during training at altitude. Thus, interrupting hypoxic exposure by training in normoxia may be a key factor in avoiding or minimizing the noxious effects that are known to occur in chronic hypoxia. When comparing HiHi and HiLo (living high and training low), it is obvious that both can induce a positive acclimatization effect and increase the oxygen transport capacity of blood, at least in 'responders', if certain prerequisites are met. The minimum dose to attain a haematological acclimatization effect is >12 h a day for at least 3 weeks at an altitude or simulated altitude of 2100-2500 m. Exposure to hypoxia appears to have some positive transfer effects on subsequent training in normoxia during and after HiLo. The increased oxygen transport capacity of blood allows training at higher intensity during and after HiLo in subsequent normoxia, thereby increasing the potential to improve some neuromuscular and cardiovascular determinants of endurance performance. The effects of hypoxic training and intermittent short-term severe hypoxia at rest are not yet clear and they require further study.
MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF‐2 in fibroblasts

Mitogen‐activated protein kinases (MAPKs) are regulated by MAPK kinases (MKKs), which are in turn regulated by MKK kinases (MKKKs). While a single MKKK can regulate several different MAPK family members, and several MKKKs can often activate the same MAPK, emerging evidence indicates a unique role for individual MKKKs in acting as signaling nodes to coordinately activate different subsets of MAPKs in response to specific cellular stimuli. Thus, while there is much apparent overlap in MAPK regulation by different MKKKs, each MKKK serves a specific purpose in regulation of unique cellular functions. The purpose of this study was to define the specific role of MEKK2, an MKKK, in MAPK regulation and cell function. MEKK2 coordinately activates the ERK5 and JNK pathways. Targeted disruption of MEKK2 expression causes loss of ERK5 and JNK activation in response to FGF‐2 in mouse embryonic fibroblasts (MEFs). FGF‐2 receptor signaling requires MEKK2 for induction of mRNA for c‐Jun, Fra‐1, and Fra‐2, components of the AP‐1 transcription complex. In FGF‐2‐stimulated MEKK2−/− fibroblasts, c‐Jun phosphorylation is inhibited, consistent with a loss of JNK activation. Thus, MEKK2 regulates AP‐1 activity at two levels, by regulating both expression of AP‐1 components and c‐Jun N‐terminal phosphorylation. One function of the AP‐1 transcription complex is to regulate cytokine gene expression. Expression of IL‐1α, IL‐1β, IL‐6, and TNFα is inhibited in MEKK2−/− fibroblasts. Bacterial lipopolysaccharide (LPS) and TNFα neither activate ERK5 nor require MEKK2 for JNK activation, demonstrating specificity of MEKK2 in FGF‐2 receptor signaling and control of cytokine gene expression. J. Cell. Physiol. 199: 140–148, 2004© 2003 Wiley‐Liss, Inc.
Adequate water supply as a rural poverty reduction strategy in developing countries: A review of the literature

Water is fundamental to health, survival and livelihoods, hence the international concern that it attracts. Globally, it is seen as an economic, social, cultural and environmental good, and to a large extent, not only a basic need but a human right. The aim of this paper is therefore to give an exposition of the role of water as a poverty reduction strategy in a rural context. This gives credence to the concept of water-related poverty that arises when water resources constrain or impact upon people’s livelihoods options or assets. A livelihoods approach to water allows us to consider the ways in which water affects people’s abilities to pursue overall sustainable livelihoods. To ensure that rural poverty reduction is realized, issues of multiple uses, sources, technologies and users of water are addressed. It is therefore recommended that access to adequate water supply, within the sustainable livelihoods framework, should be pursued if rural poverty is to be sustainably reduced .
Approximating the protection offered by a channel code in terms of bit error rate

In many joint source-channel coding applications, there is a need to assess the performance of a system on a given channel, with different combinations of channel codes. What is interesting is to know some measure of the overall bit error rate, in order to design the source and/or channel codes accordingly. We propose here an approximation of the bit error rate of the cascade of a linear block code and a memoryless binary channel. With this approximation, both of these components can be considered in this respect as a single binary symmetric channel, with known transition probability, and can be used as such for further processing. We also show some possible applications in joint source-channel coding schemes.
Occupational Risks for Nasal Cancer in Sweden

Learning ObjectivesGive examples, from a Swedish registry of males in the years 1961–2000 and of females in 1970–2000, of particular occupations that carried an increased risk of nasal cancer in general, and of adenocarcinoma and squamous-cell carcinoma in particular.Point out other occupational associations noted in the years 1960–1970.Recall specific instances where standardized incidence ratios for nasal cancer correlated with the nature and duration of exposure. Abstract An elevated risk of nasal cancer (NC) has been associated with numerous occupations but with contradicting results. We sought to address recent and current risks of NC in a nationwide study. The nationwide Swedish Family-Cancer Database was used to calculate standardized incidence ratios (SIRs) for 52 occupational groups. SIRs were adjusted for age and socioeconomic status. Among 739 male cases, significantly elevated SIRs for nasal adenocarcinoma were observed in woodworkers, teachers, and fishermen. In woodworkers, the risk increased with a longer occupational history in exposure to softwood in combination with hardwood. Electrical workers had a significant elevated risk for squamous cell carcinoma. Among 182 female cases, significantly elevated SIRs were observed in glass, ceramic, and tile workers. The study identified some known risk occupations and suggested some new ones.