Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells

Background: Fe(II)-dependent dioxygenases regulate epigenetic control, collagen maturation, and HIF degradation. Results: Iron chelation by fluoroquinolone antibiotics results in DNA and histone hypermethylation, suppression of collagen prolyl hydroxylation, and inhibition of HIF mRNA translation. Conclusion: Dioxygenase inhibition may explain renal toxicity and tendinopathy side effects of fluoroquinolones. Significance: This study suggests mechanisms for obscure fluoroquinolone-associated side effects and possible novel applications of these antibiotics as HIF antagonists. Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics.
PORTABLE DNA DETECTION SYSTEM BASED ON ULTRAFAST SEGMENT-FLOW AND FLUORESCENCE DETECTION

To detect the biological agents, the DNA detection is most usable due to the sensitivity and the selectivity. Although the key technology of DNA detection is real-time polymerase chain reaction (PCR), which uses exponential amplification of PCR and real-time detection of the amplified DNA fragments, the long thermal cycling time has been the problem to apply the rapid detection of pathogenic organisms. We developed a portable and rapid detection system based on ultrafast segment-flow PCR and fluorescent detection. Using the portable system, a model microorganism of biological warfare agent was successfully detected within 6.5 min with an enough high sensitivity.
Smoking-Dependent Reprogramming of Alveolar Macrophage Polarization: Implication for Pathogenesis of Chronic Obstructive Pulmonary Disease1

When exposed to a specific microenvironment, macrophages acquire either M1- or M2-polarized phenotypes associated with inflammation and tissue remodeling, respectively. Alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for chronic obstructive pulmonary disease (COPD), a disease characterized by lung inflammation and remodeling. Transcriptional profiling of AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers, and 12 COPD smokers was performed to test the hypothesis whether smoking alters AM polarization, resulting in a disease-relevant activation phenotype. The analysis revealed that AM of healthy smokers exhibited a unique polarization pattern characterized by substantial suppression of M1-related inflammatory/immune genes and induction of genes associated with various M2-polarization programs relevant to tissue remodeling and immunoregulation. Such reciprocal changes progressed with the development of COPD, with M1-related gene expression being most dramatically down-regulated (p < 0.0001 vs healthy nonsmokers, p < 0.002 vs healthy smokers). Results were confirmed with TaqMan real-time PCR and flow cytometry. Among progressively down-regulated M1-related genes were those encoding type I chemokines CXCL9, CXCL10, CXCL11, and CCL5. Progressive activation of M2-related program was characterized by induction of tissue remodeling and immunoregulatory genes such as matrix metalloproteinase (MMP)2, MMP7, and adenosine A3 receptor (ADORA3). Principal component analysis revealed that differential expression of polarization-related genes has substantial contribution to global AM phenotypes associated with smoking and COPD. In summary, the data provide transcriptome-based evidence that AM likely contribute to COPD pathogenesis in a noninflammatory manner due to their smoking-induced reprogramming toward M1-deactivated, partially M2-polarized macrophages.
Daily rhythms of lipid metabolic gene expression in zebra fish liver: Response to light/dark and feeding cycles

Despite numerous studies about fish nutrition and lipid metabolism, very little is known about the daily rhythm expression of lipogenesis and lipolysis genes. This research aimed to investigate the existence of daily rhythm expressions of the genes involved in lipid metabolism and their synchronization to different light/dark (LD) and feeding cycles in zebra fish liver. For this purpose, three groups of zebra fish were submitted to a 12:12 h LD cycle. A single daily meal was provided to each group at various times: in the middle of the light phase (ML); in the middle of the dark phase (MD); at random times. After 20 days of acclimation to these experimental conditions, liver samples were collected every 4 h in one 24-h cycle. The results revealed that most genes displayed a significant daily rhythm with an acrophase of expression in the dark phase. The acrophase of lipolytic genes (lipoprotein lipase – lpl, peroxisome proliferator-activated receptor – pparα and hydroxyacil CoA dehydrogenase – hadh) was displayed between ZT 02:17 h and ZT 18:31 h. That of lipogenic genes (leptin-a – lepa, peroxisome proliferator-activated receptor – pparγ, liver X receptor – lxr, insulin-like growth factor – igf1, sterol regulatory element-binding protein – srebp and fatty acid synthase – fas) was displayed between ZT 15:25 h and 20:06 h (dark phase). Feeding time barely influenced daily expression rhythms, except for lxr in the MD group, whose acrophase shifted by about 14 h compared with the ML group (ZT 04:31 h versus ZT 18:29 h, respectively). These results evidence a strong synchronization to the LD cycle, but not to feeding time, and most genes showed a nocturnal acrophase. These findings highlight the importance of considering light and feeding time to optimize lipid metabolism and feeding protocols in fish farming.
Influence of physiological status on residues of lipophilic xenobiotics in livestock

Data on the transfer of lipophilic xenobiotics from livestock feed and the environment to meat and milk are required for risk assessment purposes. Often, data are only available for lactating dairy cattle. Physiologically-based pharmacokinetic (PBPK) modeling has been used to explore differences between classes of food-producing animals. Blood and tissue levels of lipophilic xenobiotics under conditions approximating steady-state were simulated. Simulations of constant exposure were performed for lactating cows, non-lactating cattle, sheep, goats and swine. The tissue : blood partition coefficient, fat volume and fat blood flow were identified as critical determinants of predicted tissue concentrations. There may be significant breed differences in residues in milk and fat following exposure. Modeling was used to derive scaling factors that can be used to assist the extrapolation of transfer studies, carried out on lactating dairy cows, to other classes of cattle and different species.
A hybrid model for business process event and outcome prediction

Large service companies run complex customer service processes to provide communication services to their customers. The flawless execution of these processes is essential because customer service is an important differentiator. They must also be able to predict if processes will complete successfully or run into exceptions in order to intervene at the right time, preempt problems and maintain customer service. Business process data are sequential in nature and can be very diverse. Thus, there is a need for an efficient sequential forecasting methodology that can cope with this diversity. This paper proposes two approaches, a sequential k nearest neighbour and an extension of Markov models both with an added component based on sequence alignment. The proposed approaches exploit temporal categorical features of the data to predict the process next steps using higher order Markov models and the process outcomes using sequence alignment technique. The diversity aspect of the data is also added by considering subsets of similar process sequences based on k nearest neighbours. We have shown, via a set of experiments, that our sequential k nearest neighbour offers better results when compared with the original ones; our extension Markov model outperforms random guess, Markov models and hidden Markov models.
Treatment of experimental endocarditis due to penicillin-resistant Streptococcus pneumoniae

Using two strains of pneumococci for which MICs of penicillin were 1 and 4 micrograms/ml, those of cefotaxime were 0.01 and 0.5 micrograms/ml, and those of teicoplanin were 0.01 and 0.1 micrograms/ml, we studied the efficacy of different dosages of penicillin, cefotaxime, and teicoplanin in the treatment of experimental pneumococcal endocarditis in rabbits. Animals treated with dosages of penicillin G procaine needed to achieve levels in serum near the MIC for pneumococci showed a significant reduction in log10 CFU per gram of vegetation, as compared with the control (P < 0.001), although only 20% of the animals showed sterile vegetations. When levels of penicillin in serum were in the range of three- to fourfold the MIC, a greater reduction in log10 CFU per gram of vegetation was seen, and 88% of the animals showed sterile vegetations. Only the regimen of penicillin that provided concentrations in serum above the MIC throughout the interval between two doses provided constant sterilization of the cardiac vegetations. Dosages of cefotaxime and teicoplanin selected to achieve concentrations in serum equivalent to that obtained in humans during treatment resulted in levels of antimicrobial agents in serum hundreds or thousands of times higher than the MICs for the infecting strains. In terms of antimicrobial efficacy, cefotaxime and teicoplanin were equivalent to regimens with high dosages of penicillin.
The core transcriptome of mammalian placentas and the divergence of expression with placental shape

Introduction The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved. Method Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades. Results We identified a set of 115 core genes which is expressed (FPKM ≥ 10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed in Homo sapiens when compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, including EREG and WNT5A which are both associated with placental shape. Discussion 115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.
Refuge From Predation, the Benefit of Living in an Extreme Acidic Environment?

Organisms living in extreme habitats require costly adaptations to cope with these conditions. Among the suggested potential benefits that trade off these costs is refuge from predation. To study these interactions in extreme environments, samples were taken in the cave Cueva de Villa Luz, Tabasco, Mexico, where more than 32 subterranean springs, some H2S rich, rise from the floor. Hydrogen sulfide gas plus oxygen is absorbed by freshwater, and oxidation forms concentrated sulfuric acid. Snottites, whitish hollow mucous tubes, hang from the ceiling of the cave. Fluid drops from these snottites were recorded as having pH values of 0–3. We report the discovery of a new species of nematode that thrives in the highly acidic environment of the snottite. Micro CT scan of snottites reveals a complex interaction between the acidic snottite, nematodes, and abundant nematode-eating mites. The nematode adaptation to low pH probably protects them against mite predation, for which nematodes are most likely the most important source of carbon in this sulfur-driven ecosystem.
Light Enhancement Within Nanoholes in High Index Contrast Nanowires

We present systematic predictions for light enhancement in optical nanowires with nanoscale air holes in the core through numerical modeling. We show that the light intensity within such holes is strongly dependent on the hole size and refractive index of the host material and that light enhancement becomes significant only when the hole size is less than a critical value: 70 nm for silica and F2 nanowires and 50 nm for a As2S3 nanowire. High index As2S3 nanowires exhibit nearly eight times higher average mode intensity than silica glass for hole sizes of less than 10 nm. Such intensity enhancements open up new device opportunities; for example, filling nanoscale holes within silicon nanowires with silicon nanocrystals enables 30% enhancement of the nonlinear coefficient.
United States life tables, 1999.

The life tables in this report are current life tables for the United States based on age-specific death rates in 1999. Data used to prepare these life tables are 1999 final mortality statistics; July 1, 1999, population estimates; and data from the Medicare program. Presented are complete life tables by age, race, and sex. In 1999 the overall expectation of life at birth was 76.7 years, unchanged from 1998. Life expectancy increased from 1998 to 1999 for males, but decreased for females. Life expectancy increased for black males by 0.2 year (from 67.6 to 67.8) and for white males by 0.1 year (from 74.5 to 74.6). For black females, life expectancy decreased from 74.8 to 74.7 years. For white females the decrease was from 80.0 to 79.9.
Intraoperative, full-rotation, three-dimensional image (O-arm)-based navigation system for cervical pedicle screw insertion.

OBJECT The aim of this study was to retrospectively evaluate the reliability and accuracy of cervical pedicle screw (CPS) placement using an intraoperative, full-rotation, 3D image (O-arm)-based navigation system and to assess the advantages and disadvantages of the system. METHODS The study involved 21 consecutive patients undergoing posterior stabilization surgery of the cervical spine between April and December 2009. The patients, in whom 108 CPSs had been inserted, underwent screw placement based on intraoperative 3D imaging and navigation using the O-arm system. Cervical pedicle screw positions were classified into 4 grades, according to pedicle-wall perforations, by using postoperative CT. RESULTS Of the 108 CPSs, 96 (88.9%) were classified as Grade 0 (no perforation), 9 (8.3%) as Grade 1 (perforations < 2 mm, CPS exposed, and < 50% of screw diameter outside the pedicle), and 3 (2.8%) as Grade 2 (perforations between ≥ 2 and < 4 mm, CPS breached the pedicle wall, and > 50% of screw diameter outside the pedicle). No screw was classified as Grade 3 (perforation > 4 mm, complete perforation). No neurovascular complications occurred because of CPS placement. CONCLUSIONS The O-arm offers high-resolution 2D or 3D images, facilitates accurate and safe CPS insertion with high-quality navigation, and provides other substantial benefits for cervical spinal instrumentation. Even with current optimized technology, however, CPS perforation cannot be completely prevented, with 8.3% instances of minor violations, which do not cause significant complications, and 2.8% instances of major pedicle violations, which may cause catastrophic complications. Therefore, a combination of intraoperative 3D image-based navigation with other techniques may result in more accurate CPS placement.
A Local Analysis of Block Coordinate Descent for Gaussian Phase Retrieval

While convergence of the Alternating Direction Method of Multipliers (ADMM) on convex problems is well studied, convergence on nonconvex problems is only partially understood. In this paper, we consider the Gaussian phase retrieval problem, formulated as a linear constrained optimization problem with a biconvex objective. The particular structure allows for a novel application of the ADMM. It can be shown that the dual variable is zero at the global minimizer. This motivates the analysis of a block coordinate descent algorithm, which is equivalent to the ADMM with the dual variable fixed to be zero. We show that the block coordinate descent algorithm converges to the global minimizer at a linear rate, when starting from a deterministically achievable initialization point.
Verbal learning in Alzheimer’s disease: Cumulative word knowledge gains across learning trials

Abstract Research regarding learning in Alzheimer’s disease (AD) patients has been mixed. Learning capacity might be better indexed using a score that reflects the interaction between the learning slope and total recall, referred to as the Cumulative Word Learning (CWL) score. We compared a group of AD patients to normal participants using a traditional index of learning and the CWL score that were derived from the Hopkins Verbal Learning Test – Revised (HVLT-R). The HVLT-R is a supra-span, list-learning test containing 12 words from three semantic categories. The results indicated that the sample of AD patients performed within the average range, using the traditional learning z score. Although mild AD patients were not found to differ from controls in the traditional learning z score, a significant difference was noted for the CWL score. The moderate AD patients differed from the normal controls in both learning measures. Furthermore, unlike the traditional learning score, the CWL score was a significant predictor of overall cognitive functioning, as indexed using their Mini-Mental State Examination (MMSE) score. Thus, the CWL score might be a more sensitive indicator overall of total learning capacity and may be useful in staging Alzheimer’s disease because of increased resilience to floor effects. (JINS, 2009, 15, 730–739.)
Optimal impostor model in automatic speaker verification

Speaker Verification (ASV) is a binary classification task to decide whether a claimed speaker uttered sentences. This paper proposes two different algorithms for vector quantization (VQ) to speaker verification. The first algorithm named Partial Vector Quantization (Partial VQ) is based on partitioning acoustics space, represents the impostors called universal background model(UBM) and compared it to second vector quantization algorithm Reduced UBM session used for keeping the relevant training data. The present study demonstrates that several codebooks for Universal Background Models give better results. The performance of these models is evaluated on the Arabic speaker verification dataset. The VQ Partial method achieved less half total error rate for 128 codebook size better than Baseline Vector Quantization approach for 32 codebook sizes.
Expression Turnover Profiling To Monitor the Antifungal Activities of Amphotericin B, Voriconazole, and Micafungin against Aspergillus fumigatus

ABSTRACT Eight highly expressed candidate genes were selected for mRNA profiling to monitor the transcriptome kinetics of Aspergillus fumigatus strains exposed to antifungal drugs as potential biomarkers of live cells to assess treatment efficacy. Mycelia were treated with fungicidal drugs amphotericin B and voriconazole, as well as the fungistatic drug micafungin. Transcription was monitored at 0, 4, 8, and 24 h posttreatment. The expression turnover profile provides a possible tool to assess antifungal therapy effects.
Intestinal permeation enhancers.

This review addresses the field of improving oral bioavailability through the use of excipients that increase intestinal membrane permeability. The critical issues to consider in evaluating these approaches are 1) the extent of bioavailability enhancement achieved, 2) the influence of formulation and physiological variables, 3) toxicity associated with permeation enhancement, and 4) the mechanism of permeation enhancement. The categories of permeation enhancers discussed are surfactants, fatty acids, medium chain glycerides, steroidal detergents, acyl carnitine and alkanoylcholines, N-acetylated alpha-amino acids and N-acetylated non-alpha-amino acids, and chitosans and other mucoadhesive polymers. Some of these approaches have been developed to the stage of initial clinical trials. Several seem to have potential to improve oral bioavailabilities of poorly absorbed compounds without causing significant intestinal damage. In addition, the possible use of excipients that inhibit secretory transport is reviewed.
Robotic retroperitoneal surgery: a contemporary review

Purpose of reviewRobotic-assisted renal surgery is being increasingly utilized for various kidney diseases; however, the majority of these are performed via a transperitoneal approach. Retroperitoneal robotic surgery is a relatively new technique, which allows direct access to the posterolateral surface of the kidney, as well as posterior hilar structures. In this review, we summarize the most recent publications and review our experience of retroperitoneal robotic surgery. Recent findingsRetroperitoneal robotic surgery has been successfully applied to radical nephrectomy, partial nephrectomy and pyeloplasty. The current series, although few, find this approach ideal for posterior and lateral renal masses, and technically feasible with the advances in robotic technology. The retroperitoneal approach has been shown to decrease operative times, narcotic need and permit quicker return of bowel function. Furthermore, there does not appear to be any increase in perioperative complications using this approach. SummaryThe limited data using this technique offer an encouraging outlook on robotic retroperitoneal surgery. The retroperitoneal approach permits direct access to the renal hilum, no need for bowel mobilization and excellent visualization for posteriorly located renal disease.