Miracle-dz/UniFAR-FTUs huggingface dataset:
Sparfloxacin, ethambutol, and cortisol receptor inhibitor RU-40 555 treatment for disseminated Mycobacterium avium complex infection of normal C57BL/6 mice

Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.
The ability of BHRF1 to inhibit apoptosis is dependent on stimulus and cell type

The development of resistance to host defense mechanisms such as tumor necrosis factor (TNF)- and Fas-mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease. To find genes that protect cells from apoptosis, we used an expression cloning strategy and identified BHRF1, an Epstein-Barr virus (EBV) early-lytic-cycle protein with distant homology to Bcl-2, as an anti-apoptosis protein. Expression of BHRF1 in MCF-Fas cells conferred nearly complete resistance against both anti-Fas antibody and TNF-mediated apoptosis. In addition, BHRF1 protected these cells from monocyte-mediated killing but failed to protect them from killing mediated by lymphokine-activated killer cells. The ability of BHRF1 to protect MCF-Fas cells from apoptosis induced by various stimuli was identical to that of Bcl-2 and Bcl-xL. Moreover, the mechanism of action of BHRF1 resembled that of Bcl-2 and Bcl-xL as it inhibited TNF- and anti-Fas-induced activation of two enzymes participating in the apoptosis pathway, cytosolic phospholipase A2 and caspase-3/CPP32, but did not interfere with the activation of NF-kappaB-like transcription factors. A putative function of BHRF1 in EBV-infected epithelial cells may be to protect virus-infected cells from TNF- and/or anti-Fas-induced cell death in order to maximize virus production. Surprisingly, expression of neither BHRF1 nor Bcl-2 in a B-cell line, BJAB, protected the cells from anti-Fas-mediated apoptosis even though they increased the survival of serum-starved cells. Thus, the protective role of BHRF1 against apoptosis resembles that of Bcl-2 in being cell type specific and dependent on the apoptotic stimulus.
Radiology-guided forceps biopsy and airway stenting in severe airway stenosis.

PURPOSE We aimed to determine the feasibility, safety, and effectiveness of radiology-guided forceps biopsy and airway stenting in patients with severe airway stenosis. MATERIALS AND METHODS This study involved 28 patients with severe airway stenosis who underwent forceps biopsy between October 2006 and September 2011. Chest multislice computed tomography was used to determine the location and extent of stenosis. Sixteen patients had tracheal stenosis, two patients had stenosis of the tracheal carina, six patients had stenosis of the left main bronchus, and four patients had stenosis of the right main bronchus. Forceps biopsy and stenting of the stenosed area were performed under fluoroscopic guidance in digital subtraction angiography and the biopsy specimens were analyzed histopathologically. We contacted the patients via phone call and utilized a standardized questionnaire to determine their medical condition during a postoperative three-month follow-up. RESULTS The technical success rate of radiology-guided forceps biopsy was 100%. Biopsy specimens were obtained in all patients. Dyspnea was relieved immediately after stent placement. No serious complications, such as tracheal hemorrhage or perforation, mediastinal emphysema, or asphyxia, occurred. CONCLUSION Radiology-guided forceps biopsy and airway stenting can be used for the emergency treatment of severe airway stenosis. This method appears to be safe and effective, and it may be an alternative therapeutic option in patients who cannot tolerate fiberoptic bronchoscopy.
Heart rate response to professional road cycling: the Tour de France.

The aim of the present investigation was to evaluate the heart rate response of 8 professional cyclists (26+/-3 yr; 68.9+/-5.2 kg; V02max: 74.0+/-5.8 ml x kg(-1) x min(-1)) during the 3-week Tour de France as an indicator of exercise intensity. Subjects wore a heart rate telemeter during 22 competition stages and recorded data were analysed using computer software. Two reference heart rates (corresponding to the first and second ventilatory thresholds or VT1 and VT2) were used to establish three levels of exercise intensity defined as phases I (<VT1), II (VT1 -VT2) and III (<VT2). The average total time spent by each subject in each of the 3 phases respectively was approximately 71, 23 and 8 h. The relative contributions of each phase were 70, 23 and 7%. The percentage relative contribution of each phase was significantly different (p<0.01) in each of the competition stages (time trials, flat stages, "high-mountain" stages and "medium-mountain" stages). Exercise intensity was particularly high during the time trials and high mountain stages. It may be concluded that during an endurance event such as the Tour de France, although the overall contribution of moderate (VT1 to VT2) or high intensity exercise (>VT2) is substantially lower than that of light, aerobic exercise (<VT1), a clear distinction must be made between the different type of stages (i.e. easy, flat parcours vs mountain stages or time trials) and the role of each cyclist in the team must be also considered.
Distinct DNA Methylomes of Human Placentas Between Pre-Eclampsia and Gestational Diabetes Mellitus

Background: The placenta acts not only as a conduit of nutrient and waste exchange between mother and developing fetus but also functions as a regulator of the intrauterine environment. Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are leading causes of complications during pregnancy. Pathophysiologies show that they are associated with one another. Epigenetics provides a link between environmental factors that have previously been linked to poor pregnancy outcomes and fetal programming. Methods and Results: The present study investigated genome-wide DNA methylation changes in PE and GDM compared with control subjects through DNA methylation microarray. We found that the methylation patterns of placentas from PE and GDM women were similar; 64.4% of the annotated genes with differential methylation presented concordant changes between PE and GDM patients. Significantly, the same functional processes were affected by PE and GDM, with cell adhesion and cell differentiation being the most populated clusters and including genes related to carbohydrate metabolism and lipid metabolism. Conclusion: Our work showed that of DNA methylation patterns in human placentas are reliably and significantly associated with PE and GDM. DNA methylation status in the human placenta can function as a marker for the intrauterine environment and potentially play a functional role in PE and GDM development.
Relationship of childhood physical and sexual abuse to adult bipolar disorder.

OBJECTIVES To characterize whether adult depressives with either bipolar or unipolar disorder differ in the prevalence of childhood sexual or physical abuse. METHOD The investigators reviewed data from patients who were evaluated over a 2-year period by a semi-structured clinical interview. In total, 333 cases with a bipolar or unipolar diagnosis were included in the present study. RESULTS A childhood history of abuse, in particular sexual abuse, was significantly more frequent in bipolar subjects compared with unipolar subjects. Consistent with previous studies, women reported higher rates of sexual abuse than men, although no interaction by diagnosis was shown. Sexual abuse incidence in male samples was markedly dissimilar, with male bipolar subjects demonstrating a significantly increased rate of sexual abuse and combined sexual and physical abuse compared with unipolar male subjects. CONCLUSION The increased incidence of sexual abuse in women supports growing evidence of gender differences in sexual abuse among adult depressives. In contrast to literature reports, the finding that male bipolar patients have significantly increased rates of sexual abuse histories suggests differences in psychiatric depressive subgroups. This result may reflect the particular characteristics of our cohort (treatment resistant, privately insured, and educated). Further work will aid in characterizing sexual abuse prevalence in other male bipolar samples.
Revisiting the Master-Slave Architecture in Multi-Agent Deep Reinforcement Learning

Many tasks in artificial intelligence require the collaboration of multiple agents. We exam deep reinforcement learning for multi-agent domains. Recent research efforts often take the form of two seemingly conflicting perspectives, the decentralized perspective, where each agent is supposed to have its own controller; and the centralized perspective, where one assumes there is a larger model controlling all agents. In this regard, we revisit the idea of the master-slave architecture by incorporating both perspectives within one framework. Such a hierarchical structure naturally leverages advantages from one another. The idea of combining both perspective is intuitive and can be well motivated from many real world systems, however, out of a variety of possible realizations, we highlights three key ingredients, i.e. composed action representation, learnable communication and independent reasoning. With network designs to facilitate these explicitly, our proposal consistently outperforms latest competing methods both in synthetics experiments and when applied to challenging StarCraft micromanagement tasks.
Wireless sensor network using hybrid TDOA/RSS tracking of uncooperative targets

Accurate tracking of uncooperative wireless target devices, particularly WiFi devices, is valuable for many commercial, industrial and security applications. Tracking based on received signal strength is widely used, but has limited accuracy. The use of time-of-arrival (TOA) measurements can improve accuracy, but as most target devices cannot accurately measure TOA the device is not able to cooperate and time-difference-of-arrival (TDOA) techniques are required. In this paper we present a sensor network for tracking target devices based on both received signal strength and TDOA. A new hybrid algorithm combining both types of measurements based on a particle filter is presented, and shown to perform better than either technique alone. The use of difference of RSS measurements is also shown to give better tracking performance than RSS as errors in the assumed transmit power from the target do not affect the results.
Early life establishment of site-specific microbial communities in the gut

Fecal sampling is widely utilized to define small intestinal tissue-level microbial communities in healthy and diseased newborns. However, this approach may lead to inaccurate assessments of disease or therapeutics in newborns because of the assumption that the taxa in the fecal microbiota are representative of the taxa present throughout the gastrointestinal tract. To assess the stratification of microbes in the newborn gut and to evaluate the probable shortcoming of fecal sampling in place of tissue sampling, we simultaneously compared intestinal mucosa and fecal microbial communities in 15 neonates undergoing intestinal resections. We report three key results. First, when the site of fecal and mucosal samples are further apart, their microbial communities are more distinct, as indicated by low mean Sørensen similarity indices for each patient's fecal and tissue microbiota. Second, two distinct niches (intestinal mucosa and fecal microbiota) are evident by principal component analyses, demonstrating the critical role of sample source in defining microbial composition. Finally, in contrast to adult studies, intestinal bacterial diversity was higher in tissue than in fecal samples. This study represents an unprecedented map of the infant microbiota from intestinal mucosa and establishes discernable biogeography throughout the neonatal gastrointestinal tract. Our results question the reliance on fecal microbiota as a proxy for the developing intestinal microbiota. Additionally, the robust intestinal tissue-level bacterial diversity we detected at these early ages may contribute to the maturation of mucosal immunity.
NGF‐resistant PC12 cell death induced by arachidonic acid is accompanied by a decrease of active PKC zeta and nuclear factor kappa B

Inflammation and the associated release of inflammatory cytokines such as tumor necrosis factor alpha (TNFα) may be a component of neurodegenerative diseases associated with aging or chronic HIV‐1 infection. Most of the neurons that are affected under these conditions require a constant supply of trophic factors such as nerve growth factor (NGF) for survival. NGF acts via binding to a specific tyrosine kinase receptor (TrkA). NGF also binds to the common neurotrophin receptor (p75NTR), a member of the TNFα receptor (TNFR‐I) superfamily, whose function may be to modulate apoptosis via the release of ceramide and the activation of the transcription factor nuclear factor kappa B (NFκB). The similarity between p75NTR and TNFR‐I signal transduction pathways suggests that one of the mechanisms by which TNFα affects neuronal survival is by impacting upon these pathways that normally promote NGF support of neurons. Here we show that arachidonic acid (AA), a signaling lipid potentially associated with TNFR‐I signal cascade, induces apoptosis in PC12 cells through inhibition of both protein kinase C zeta (PKCζ) and NFκB activity. We also show that apoptosis induced by AA cannot be prevented by NGF. These data support the idea that PKCζ and NFκB are both essential signaling elements for mediating NGF‐promoted rescue from apoptosis. Our results also suggest that AA, an inflammatory signal lipid induced by TNFα via binding to TNFR‐I, may reduce neuronal survival by inhibiting elements of the signal cascade induced by NGF. J. Neurosci. Res. 57:219–226, 1999. © 1999 Wiley‐Liss, Inc.
‘Piggy-Back’ Transport of Xenopus Hyaluronan Synthase (XHAS1) via the Secretory Pathway to the Plasma Membrane

Abstract Hyaluronan is the sole glycosaminoglycan whose biosynthesis takes place directly at the plasma membrane. The mechanism by which hyaluronan synthase (HAS) becomes inserted there, as well as the question of how the enzyme discriminates between particular membrane species in polarized cells, are largely unknown. In vitro translation of HAS suggested that the nascent protein becomes stabilized in the presence of microsomal membranes, but would not insert spontaneously into membranes after being translated in the absence of those. We therefore monitored the membrane attachment of enzymatically active fusion proteins consisting of Xenopus HAS1 and green fluorescent protein shortly after de novo synthesis in Vero cells. Our data strongly suggest that HAS proteins are directly translated on the ER membrane without exhibiting an N-terminal signal sequence. From there the inactive protein is transferred to the plasma membrane via the secretory pathway. For unknown reasons, HAS inserted into membranes other than the plasma membrane remains inactive.
Implantation of personalized, biocompatible mitral annuloplasty rings: feasibility study in an animal model.

OBJECTIVES Implantation of an annuloplasty ring is an essential component of a durable mitral valve repair. Currently available off-the-shelf rings still do not cover all the variations in mitral annulus anatomy and pathology from subject to subject. Computed tomography (CT) and echo imaging allow for 3-D segmentation of the mitral valve and mitral annulus. The concept of tailored annuloplasty rings has been proposed although, to date, no surgically applicable implementation of patient-specific annuloplasty rings has been seen. The objective of this trial was to prove the concept of surgical implantation of a model-guided, personalized mitral annuloplasty ring, manufactured based on individual CT-scan models. METHODS ECG-gated CT angiography was performed in six healthy pigs under general anaesthesia. Based on the individual shape of the mitral annulus in systole, a customized solid ring with integrated suturing holes was designed and manufactured from a biocompatible titanium alloy by a rapid process using laser melting. The ring was implanted three days later and valve function was assessed by intraoperative echocardiography. The macroscopic annulus-annuloplasty match was assessed after heart explantation. RESULTS CT angiography provided good enough image quality in all animals to allow for segmentation of the mitral annulus. The individually tailored mitral rings were manufactured and successfully implanted in all pigs. In 50%, a perfect matching of the implanted ring and the mitral annulus was achieved. In one animal, a slight deviation of the ring shape from the circumference was seen postoperatively. The rings implanted in the first two animals were significantly oversized but the deviation did not affect valve competence. CONCLUSIONS CT image quality and accuracy of the dimensions of the mitral annulus were sufficient for digital modelling and rapid manufacturing of mitral rings. Implantation of individually tailored annuloplasty rings is feasible.
Application of electromagnetic navigation in surgical treatment of intracranial tumors: analysis of 12 cases.

OBJECTIVE To explore the application and characteristics of electromagnetic navigation in neurosurgical operation. METHODS Neurosurgical operations with the assistance of electromagnetic navigation were performed in 12 patients with intracranial tumors. RESULTS Total removal of the tumor was achieved in 8 cases, subtotal removal in 3 and removal of the majority of the tumor in 1 case. The error in the navigation averaged 1.9+/-0.9 mm and the time consumed by preoperative preparation was 19+/-2 min with the exception in 1 case. CONCLUSION In comparison with optic navigation, electromagnetic navigation offers better convenience and absence of signal blockage, and with a head frame, automatic registration can be achieved.
cAMP response element–binding protein is expressed at high levels in human ovarian adenocarcinoma and regulates ovarian tumor cell proliferation

Approximately 90% of human ovarian tumors result from transformation of ovarian surface epithelial cells. It has been hypothesized that repeated destruction of the epithelial cells during ovulation, followed by proliferation and migration of epithelial cells to restore the ovarian surface, renders these cells susceptible to mutagenic events. One of the proteins found to promote ovarian surface epithelial cell survival and proliferation was the transcription factor, cAMP response element–binding protein (CREB). Thus, the objective of this study was to determine whether CREB was also highly expressed in tumor cells originating from the ovarian epithelium. Using an ovarian cancer tissue array, it was observed that approximately 54% of the epithelial-derived human ovarian tumors displayed moderate or high levels of CREB immunostaining, while none of the normal ovarian samples did. Comparison of CREB levels in a human ovarian tumor cell line to those of a normal ovarian epithelial cell line revealed elevated levels of CREB and phosphorylated CREB in the ovarian tumor cells. To determine whether CREB regulated proliferation and/or apoptosis in the ovarian tumor cell line, CREB expression was suppressed using RNA interference. Decreased CREB expression significantly reduced ovarian tumor cell proliferation, while there was no effect on apoptosis in these cells. Finally, we showed that CREB is highly expressed in an in vivo murine model of ovarian tumorigenesis. Therefore, CREB is frequently overexpressed in ovarian cancer where it appears to promote cell proliferation.
A Convex Similarity Index for Sparse Recovery of Missing Image Samples

This paper investigates the problem of recovering missing samples using methods based on sparse representation adapted especially for image signals. Instead of $l_2$-norm or Mean Square Error (MSE), a new perceptual quality measure is used as the similarity criterion between the original and the reconstructed images. The proposed criterion called Convex SIMilarity (CSIM) index is a modified version of the Structural SIMilarity (SSIM) index, which despite its predecessor, is convex and uni-modal. We derive mathematical properties for the proposed index and show how to optimally choose the parameters of the proposed criterion, investigating the Restricted Isometry (RIP) and error-sensitivity properties. We also propose an iterative sparse recovery method based on a constrained $l_1$-norm minimization problem, incorporating CSIM as the fidelity criterion. The resulting convex optimization problem is solved via an algorithm based on Alternating Direction Method of Multipliers (ADMM). Taking advantage of the convexity of the CSIM index, we also prove the convergence of the algorithm to the globally optimal solution of the proposed optimization problem, starting from any arbitrary point. Simulation results confirm the performance of the new similarity index as well as the proposed algorithm for missing sample recovery of image patch signals.