Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C infection: the quest for new treatment strategies

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Relationships between altitude, triatomine (Triatoma dimidiata) immune response and virulence of Trypanosoma cruzi, the causal agent of Chagas' disease

Little is known about how the virulence of a human pathogen varies in the environment it shares with its vector. This study focused on whether the virulence of Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae), the causal agent of Chagas' disease, is related to altitude. Accordingly, Triatoma dimidiata (Hemiptera: Reduviidae) specimens were collected at three different altitudes (300, 700 and 1400 m a.s.l.) in Chiapas, Mexico. The parasite was then isolated to infect uninfected T. dimidiata from the same altitudes, as well as female CD‐1 mice. The response variables were phenoloxidase (PO) activity, a key insect immune response, parasitaemia in mice, and amastigote numbers in the heart, oesophagus, gastrocnemius and brain of the rodents. The highest levels of PO activity, parasitaemia and amastigotes were found for Tryp. cruzi isolates sourced from 700 m a.s. l. , particularly in the mouse brain. A polymerase chain reaction‐based analysis indicated that all Tryp. cruzi isolates belonged to a Tryp. cruzi I lineage. Thus, Tryp. cruzi from 700 m a.s. l. may be more dangerous than sources at other altitudes. At this altitude, T. dimidiata is more common, apparently because the conditions are more beneficial to its development. Control strategies should focus activity at altitudes around 700 m a.s. l. , at least in relation to the region of the present study sites.
Correlation of distortion noise between the branches of MIMO transmit antennas

Despite the tremendous research effort spent on MIMO systems - very few papers address the impact of hardware imperfections. In this paper we analyze the distortion noise of the transmitter branches of a MIMO transmitter. In particular we analyze the cross-correlation of the distortion noises for the case that the transmitted signals are correlated. This case arises when there is just a single stream being transmitted with beamforming or in the case of multiple streams and linear precoding. We analyze the problem in two ways: using analytical derivations and using measurements on our testbed. In the analytical case we assume a transmitter impaired by a 3rd order non-linearity. For this scenario we find that the absolute correlation coefficient of the distortion noises is given by the absolute value of the correlation coefficients of the input signals to the power of three, while the phase is the same as that of the input signal. Our measurements also show good agreement between measurements and analytical results. It seems to suggest that the distortion noises can be regarded as practically independent whenever there are two or more modulation streams being transmitted (spatial multiplexing). In a single-stream scenario, the distortion noise will tend to have the same spatial distribution as the desired signal.
The Positioning system for KM3NeT

The paper describes the implementation of a hybrid positioning system based on tilt and compass sensors, integrated into an electronic board, and an acoustic positioning system to be installed aboard KM3NeT. The acoustic system will be capable to fulfil detector relative and absolute positioning, to provide data for cross-fertilisation with Earth and Sea science (bio-acoustics and environmental monitoring) and to allow studies for neutrino acoustic detection. Tilt and Compass boards installed in each optical module provide information about the DOM orientation.
Dynamics of the nonclassical diffusion equations

We consider the dynamical behavior of the nonclassical diffusion equation with critical nonlinearity for both autonomous and nonautonomous cases. For the autonomous case, we obtain the existence of a global attractor when the forcing term only belongs to H−1, this result simultaneously resolves a problem in Acta Mathematicae Applicatae Sinica 18 (2002), 273–276 related to the critical exponent. For the nonautonomous case, assumed that the time-dependent forcing term is translation bounded instead of translation compact, we first prove the asymptotic regularity of solutions, then the existence of a compact uniform attractor together with its structure and regularity has been obtained; finally, we show the existence of (nonautonomous) exponential attractors.
Essential role of Helicobacter pyloriγ‐glutamyltranspeptidase for the colonization of the gastric mucosa of mice

Constitutive expression of γ‐glutamyltranspeptidase (GGT) activity is common to all Helicobacter pylori strains, and is used as a marker for identifying H. pylori isolates. Helicobacter pylori GGT was purified from sonicated extracts of H. pylori strain 85P by anion exchange chromatography. The N‐terminal amino acid sequences of two of the generated endoproteolysed peptides were determined, allowing the cloning and sequencing of the corresponding gene from a genomic H. pylori library. The H. pylori ggt gene consists of a 1681 basepair (bp) open reading frame encoding a protein with a signal sequence and a calculated molecular mass of 61 kDa. Escherichia coli clones harbouring the H. pylori ggt gene exhibited GGT activity at 37°C, in contrast to E. coli host cells (MC1061, HB101), which were GGT negative at 37°C. GGT activity was found to be constitutively expressed by similar genes in Helicobacter felis, Helicobacter canis, Helicobacter bilis, Helicobacter hepaticus and Helicobacter mustelae. Western immunoblots using rabbit antibodies raised against a His‐tagged‐GGT recombinant protein demonstrated that H. pylori GGT is synthesized in both H. pylori and E. coli as a pro‐GGT that is processed into a large and a small subunit. Deletion of a 700 bp fragment within the GGT‐encoding gene of a mouse‐adapted H. pylori strain (SS1) resulted in mutants that were GGT negative yet grew normally in vitro. These mutants, however, were unable to colonize the gastric mucosa of mice when orally administered alone or together (co‐infection) with the parental strain. These results demonstrate that H. pylori GGT activity has an essential role for the establishment of the infection in the mouse model, demonstrating for the first time a physiological role for a bacterial GGT enzyme.
Electrocardiographic Findings in Psoriatic Arthritis: A Case-Controlled Study

Objective We assessed cardiac conduction properties in patients with psoriatic arthritis (PsA). Methods Electrocardiogram (ECG) scans of 92 patients with PsA were compared to 92 age and sex matched nonpsoriatic, nonarthritic patients from general practice serving as controls. Results PR interval was found to be significantly longer in the PsA group compared to controls, 159.6 ± 21 ms versus 151.3 ± 26 ms, respectively (p = 0.021). No statistical difference was found with respect to the QRS interval or other atrial or ventricular conduction disturbances studied. No correlation was found between the PR interval and disease duration or PsA subtype. The use of non-steroidal antiinflammatory drugs did not affect the PR interval. Methotrexate was not found to influence the PR interval, compared to other disease modifying antirheumatic drugs. Two PsA patients (2.1%) had a PR interval > 0.2 ms. Their prolonged PR interval could not be explained by medication use. The abnormal prolongation of the PR interval was asymptomatic, requiring no additional intervention. No patient had complete heart block. Conclusion Our study may suggest subtle involvement of the atrioventricular node in patients with PsA.
Antiherpesvirus action of atropine

The antimuscarinic compound atropine shows an antiherpesvirus effect as measured by the protection of the cell monolayer and the reduction of the formation of new infectious virus. Atropine at a concentration of 200 micrograms/ml blocks the production of new infectious herpes simplex virus-type 1 virions. At that concentration, it has almost no effect on cellular or viral protein synthesis even when atropine is present from the beginning of the infection. The glycosylation of viral proteins is almost totally blocked when atropine is added. Although the viral proteins are underglycosylated, the formation of new herpes simplex virus type 1 virions takes place. The virions formed in the presence of atropine are noninfectious, and their protein composition, as assessed by labeling with [35S]methionine, is similar to that of the control, except that they are not glycosylated.
Incidence and psychological-behavioral characteristics of refractory functional dyspepsia: a large, multi-center, prospective investigation from China.

AIM To explore the incidence and psychological and behavioral characteristics of refractory functional dyspepsia (RFD) in China. METHODS The subjects of this study were 1341 new outpatients with functional dyspepsia (FD) who were diagnosed according to the Rome III criteria at four hospitals in Guangdong Province between June and September 2012, and 100 healthy volunteers. All subjects completed questionnaires and scales administered. RESULTS Three-hundred and twenty-seven of the 1341 patients with FD had RFD (24.4%). Patients with RFD had a longer disease duration and a more severe form of the disease than patients with non-refractory FD (NRFD). The prevalence of depression and anxiety symptoms was higher in patients with RFD than in patients with NRFD. The prevalence of unhealthy eating behaviors, lack of physical activity, and sleeping disorders was higher in patients with RFD than in patients with NRFD. Patients with RFD sought medical advice on more occasions and spent more money on treatment than patients with NRFD. Finally, patients with RFD had poorer quality of life than patients with NRFD. CONCLUSION RFD is not rare in clinical practice and should get attention by patients and doctors because of its long duration, severe symptoms, and associations with abnormal psychology and poor quality of life.
On robustness of the Shiryaev–Roberts change-point detection procedure under parameter misspecification in the post-change distribution

ABSTRACT The gist of the quickest change-point detection problem is to detect the presence of a change in the statistical behavior of a series of sequentially made observations, and do so in an optimal detection-speed-versus-“false-positive”-risk manner. When optimality is understood either in the generalized Bayesian sense or as defined in Shiryaev's multi-cyclic setup, the so-called Shiryaev–Roberts (SR) detection procedure is known to be the “best one can do”, provided, however, that the observations’ pre- and post-change distributions are both fully specified. We consider a more realistic setup, viz. one where the post-change distribution is assumed known only up to a parameter, so that the latter may be misspecified. The question of interest is the sensitivity (or robustness) of the otherwise “best” SR procedure with respect to a possible misspecification of the post-change distribution parameter. To answer this question, we provide a case study where, in a specific Gaussian scenario, we allow the SR procedure to be “out of tune” in the way of the post-change distribution parameter, and numerically assess the effect of the “mistuning” on Shiryaev's (multi-cyclic) Stationary Average Detection Delay delivered by the SR procedure. The comprehensive quantitative robustness characterization of the SR procedure obtained in the study can be used to develop the respective theory as well as to provide a rational for practical design of the SR procedure. The overall qualitative conclusion of the study is an expected one: the SR procedure is less (more) robust for less (more) contrast changes and for lower (higher) levels of the false alarm risk.
Mildly Oxidized Low Density Lipoprotein Rapidly Stimulates via Activation of the Lysophosphatidic Acid Receptor Src Family and Syk Tyrosine Kinases and Ca2+ Influx in Human Platelets*

In contrast to native low density lipoprotein (LDL), mildly oxidized LDL (mox-LDL) induced platelet shape change and stimulated during shape change the tyrosine phosphorylation of specific proteins including Syk; the translocation of Src, Fyn, and Syk to the cytoskeleton; and the increase of cytosolic Ca2+ due to mainly Ca2+ entry. The stimulation of these early signal pathways by mox-LDL was inhibited by desensitization of the lysophosphatidic acid (LPA) receptor and specific LPA receptor antagonists, was independent of the αIIbβ3-integrin, and was mimicked by LPA. Stimulation of tyrosine phosphorylation and Syk activation were independent of the increase of cytosolic Ca2+ and were suppressed by genistein and two specific inhibitors of the Src family tyrosine kinases, PP1 and PD173956. In contrast to PP1 and PD 173956, genistein prevented shape change by mox-LDL. The results indicate that mox-LDL, through activation of the LPA receptor, stimulates two separate early signal pathways, (a) Src family and Syk tyrosine kinases, and (b) Ca2+ entry. The activation of these early signaling pathways by mox-LDL probably plays a role in platelet responses subsequent to shape change. The inhibition of mox-LDL-induced platelet activation by LPA receptor antagonists or dietary isoflavonoids such as genistein could have implications in the prevention and therapy of cardiovascular diseases.
Recipe or performing art?

This article explores the tensions and incongruities between conventional thesis presentation and the principles of action research. Through the experiences of the authors alternative approaches to thesis structure are proposed which are argued to be more congruent with the epistemological, methodological and ethical aspects of action research. Consistent with our arguments, the article is presented as a play. Act I considers the tensions facing research students wishing to write up their action research in the context of conventional thesis writing requirements; Act II consists of four ‘scenes’, each of which illustrates a key learning arising from our own stories: writing in the researcher as central to the research; staying true to the unfolding research story; using metaphor; and finally, weaving literature throughout the thesis. Act III considers the challenges of examination in the face of breaking with tradition. We conclude with a ‘curtain call’ from the narrator that offers a reflexive engagement with the main themes of the article.
Early–life‐stage toxicity in offspring from exposed parent medaka, Oryzias latipes, to mixtures of tributyltin and polychlorinated biphenyls

The present study examined the effectsoftributyltin (TBT), polychlorinated biphenyls (PCBs), and mixtures ofboth chemicals on reproduction in Japanese medaka, Oryzias latipes. For 21 d we gave groups of medaka freeze‐dried brine shrimp flakes contaminated with a mixture of either 0, 1, 5, or 25 μg TBT g1 plus 0 or 25 μg PCBs g1. We measured the fecundity and fertility of the parent fish and assessed the deformity, hatchability, time‐to‐hatching, and swim‐up failure rate of the next generation. Fertilization success in the third week of the administration period was significantly decreased by administration of 25 μg TBT g−1 (77%) compared with the control group (87%). Both TBT and PCBs were transferred maternally into the eggs of the next generation, causing early life–stage toxicity. Administration of 1 μg TBT g1 was not toxic to embryological development, but abnormal eye development (i.e., small eyes or no eyes) occurred when TBT at the same concentration was mixed with PCBs (6.4%). Administration of TBT alone significantly decreased hatchability and increased swim‐up failure, and administration of PCBs alone significantly increased time‐to‐hatching. Statistical analysis by two‐way analysis of variance detected an interaction between TBT and PCBs in these three parameters. TBT induces abnormal development of the eyes, reduced hatchability, and increased swim‐up failure, whereas PCBs delay time‐to‐hatching. Administration of mixtures of TBT and PCBs has more adverse effects on the developmental stage of medaka than does that of each chemical alone.
Comprehensive genetic and functional characterization of IPH‐926: a novel CDH1‐null tumour cell line from human lobular breast cancer

Infiltrating lobular breast cancer (ILBC) is a clinically and biologically distinct tumour entity defined by a characteristic linear cord invasion pattern and inactivation of the CDH1 tumour suppressor gene encoding for E‐cadherin. ILBCs also lack β‐catenin expression and show aberrant cytoplasmic localization of the E‐cadherin binding protein p120‐catenin. The lack of a well‐characterized ILBC cell line has hampered the functional characterization of ILBC cells in vitro. We report the establishment of a permanent ILBC cell line, named IPH‐926, which was derived from a patient with metastatic ILBC. The DNA fingerprint of IPH‐926 verified genetic identity with the patient and had no match among the human cell line collections of several international biological resource banks. IPH‐926 expressed various epithelial cell markers but lacked expression of E‐cadherin due to a previously unreported, homozygous CDH1 241ins4 frameshift mutation. Detection of the same CDH1 241ins4 mutation in archival tumour tissue of the corresponding primary ILBC proved the clonal origin of IPH‐926 from this particular tumour. IPH‐926 also lacked β‐catenin expression and showed aberrant cytoplasmic localization of p120‐catenin. Array‐CGH analysis of IPH‐926 revealed a profile of genomic imbalances that included many distinct alterations previously observed in primary ILBCs. Spectral karyotyping of IPH‐926 showed a hyperdiploid chromosome complement and numerous clonal, structural aberrations. IPH‐926 cells were anti‐cancer drug‐resistant, clonogenic in soft agar, and tumourigenic in SCID mice. In xenograft tumours, IPH‐926 cells recapitulated the linear cord invasion pattern that defines ILBCs. In summary, IPH‐926 significantly extends the biological spectrum of the established breast cancer cell lines and will facilitate functional analyses of genuine human ILBC cells in vitro and in vivo. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Role of surgery and chemotherapy for peripheral lymph node tuberculosis

A total of 105 patients with peripheral lymph node tuberculosis were treated by either surgical excision and chemotherapy or chemotherapy alone. The cervical nodes were affected in 98 patients, axillary nodes in four and inguinal nodes in three. Biopsy of the lymph nodes confirmed the diagnosis in all cases. Thirty‐five patients who had sinus, ulcer or abscess underwent excision of the lymph nodes with drainage of the abscess, or resection of the sinus or ulcer. The remaining 70 patients received only chemotherapy. Chemotherapy in all patients consisted of isoniazid and ethambutol for 18 months. Of the 35 patients treated with surgery and chemotherapy, two had gaping wounds, one infection and one cellulitis of the face and neck. After 3 months, one patient had recurrence of the lymph node mass and one recurrence of a sinus; these were excised. Of the 70 patients treated only with chemotherapy, 13 were lost to follow‐up. Four had non‐healing wounds at the biopsy site, six wound infection and two sinus formation. Five of these patients had persistent lymph node masses, which were excised after 3 months. The remaining 52 patients had no recurrence.
Tacrolimus and the Risk of Solid Cancers After Liver Transplant: A Dose Effect Relationship

Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single‐center study was conducted between 1995 and 2008 and is based on 247 tacrolimus‐treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93–15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57–2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.
Improving strategies for detecting genetic patterns of disease susceptibility in association studies

The analysis of gene interactions and epistatic patterns of susceptibility is especially important for investigating complex diseases such as cancer characterized by the joint action of several genes. This work is motivated by a case‐control study of bladder cancer, aimed at evaluating the role of both genetic and environmental factors in bladder carcinogenesis. In particular, the analysis of the inflammation pathway is of interest, for which information on a total of 282 SNPs in 108 genes involved in the inflammatory response is available. Detecting and interpreting interactions with such a large number of polymorphisms is a great challenge from both the statistical and the computational perspectives. In this paper we propose a two‐stage strategy for identifying relevant interactions: (1) the use of a synergy measure among interacting genes and (2) the use of the model‐based multifactor dimensionality reduction method (MB‐MDR), a model‐based version of the MDR method, which allows adjustment for confounders. Copyright © 2008 John Wiley & Sons, Ltd.
A randomized controlled pilot study of VO2 max testing: a potential model for measuring relative in vivo efficacy of different red blood cell products

Randomized trials, for example, RECESS, comparing “young” (median, 7‐day) versus “middle‐aged” (median, 28‐day) red blood cells (RBCs), showed no difference in outcome. These data are important; however, they do not inform us about the safety and effectiveness of the oldest RBCs, which some patients receive. It may not be feasible to conduct a clinical trial randomizing patients to receive the oldest blood. Therefore, we propose strenuous exercise (VO2 max testing) as a model to study the relative efficacy to increase oxygen delivery to tissue of different RBC products, for example, extremes of storage duration.