Miracle-dz/UniFAR-FTUs huggingface dataset:
Once-daily intramuscular amikacin for outpatient treatment of lower urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli in children

Background The rise in community-acquired urinary tract infections (UTIs) with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli strains raises the question of how to treat these infections effectively in pediatric outpatients. Amikacin has shown promising in vitro activity against ESBL-producing urinary isolates of E. coli; however, clinical data are limited. Objective To investigate the clinical and microbiological outcomes of community-acquired lower UTIs caused by ESBL-producing E. coli treated with outpatient amikacin in children. Materials and methods A retrospective cohort study was performed on pediatric patients aged ≥2 to 18 years treated as outpatients with intramuscular amikacin (given at a dose of 15 mg/kg/day once daily) for community-acquired lower UTIs caused by ESBL-producing E. coli, between January 2015 and December 2016. Results A total of 53 pediatric patients (38 females) were enrolled in this study. The median age was 4.7 years (range 3–12 years). All E. coli isolates were susceptible to amikacin with minimum inhibitory concentrations of ≤4 mg/L. The median duration of amikacin treatment was 6 days (range 3–7 days). Favorable clinical and bacteriological responses were observed in 51 of 53 (96%) patients. Development of resistance during treatment with amikacin was seen in only 1 patient (2%), who failed to respond to amikacin treatment and developed acute pyelonephritis with bacteremia. Relapsed lower UTI after initial treatment response occurred in 1 patient (2%) 2 weeks after completion of amikacin treatment. All patients had normal serum creatinine values at baseline, and no significant nephrotoxicity or ototoxicity was observed in any of the patients. Conclusion Our study suggests that once-daily intramuscular amikacin could be an alternative option for outpatient treatment of community-acquired lower UTIs caused by amikacin-susceptible ESBL-producing E. coli in pediatric patients with normal renal function, when there are no suitable oral antibiotics.
CoV(t)-based Traffic and Queuing Modeling

Accurate performance evaluation and network dimensioning are required for the design and the deployment of new telecommunication networks based on packet-switching technologies (e.g., Ethernet, IP, G/T-MPLS, etc.). In this context, network engineers need simple, efficient and realistic traffic models. In this paper we investigate traffic modeling based on the coefficient of variation CoV(t) of the data rate observed at different time scales t. We derive a simplified CoV(t)-based traffic model, the novelty being that it requires only four parameters easily tunable with the following characteristics: the mean-rate mu, the link capacity C constraining the traffic, the Hurst parameter H and the transition time scale t0 linked to the burst duration. Confronted to some real traffic traces, our model proves to be accurate. We illustrate how to use it in analytical performance calculation by applying it to the "ideal switch" case: thanks to our four-parameter simple model, one can derive formulas for node performance estimation or dimensioning. Finally, we propose a new fitting procedure that automatically translates the four-parameter traffic model of this paper into a superposition of Markov fluid ON-OFF sources, and that is simpler than already existing fitting procedures. This superposition can be used to generate traffic for packet switch simulations, simplifying the set-up of the test traffic to the specification of the four parameters we mentioned above.
Co-translocation of a Periplasmic Enzyme Complex by a Hitchhiker Mechanism through the Bacterial Tat Pathway*

Bacterial periplasmic nickel-containing hydrogenases are composed of a small subunit containing a twin-arginine signal sequence and a large subunit devoid of an export signal. To understand how the large subunit is translocated into the periplasm, we cloned the hyb operon encoding the hydrogenase 2 ofEscherichia coli, constructed a deletion mutant, and studied the mechanism of translocation of hydrogenase 2. The small subunit (HybO) or the large subunit (HybC) accumulated in the cytoplasm as a precursor when either of them was expressed in the absence of the other subunit. Therefore, contrary to most classical secretory proteins, the signal sequence of the small subunit itself is not sufficient for membrane targeting and translocation if the large subunit is missing. On the other hand, the small subunit was required not only for membrane targeting of the large subunit, but also for the acquisition of nickel by the large subunit. Most interestingly, the signal sequence of the small subunit determines whether the large subunit follows the Sec or the twin-arginine translocation pathway. Taken together, these results provide for the first time compelling evidence for a naturally occurring hitchhiker co-translocation mechanism in bacteria.
Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6

We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T‐lymphocyte (CTL) responses specific for SOX6 to destroy glioma can be generated in vivo, we treated glioma‐bearing mice by vaccination with a plasmid DNA encoding murine full‐length SOX6 protein. Following SOX6‐DNA vaccination, CTLs specific for SOX6‐expressing glioma cells were induced, while normal autologous‐cells that had restrictedly expressed SOX6 during embryogenesis were not destroyed. Furthermore, DNA vaccination with SOX6 exerted protective and therapeutic antitumor responses in the glioma‐bearing mice. This antitumor activity was abrogated by the depletion of CD4 positive T cells and/or CD8 positive T cells. These results suggest that the SOX6 protein has multiple CTL and helper epitopes to induce antitumor activity and the effectiveness of SOX6‐DNA vaccine for the prevention and treatment of glioma. © 2008 Wiley‐Liss, Inc.
Cusp excursion in hyperbolic manifolds and singularity of harmonic measure

We generalize the notion of cusp excursion of geodesic rays by introducing for any $k \geq 1$ the $k^{th}$ excursion in the cusps of a hyperbolic $N$-manifold of finite volume. We show that on one hand, this excursion is at most linear for geodesics that are generic with respect to the hitting measure of a random walk. On the other hand, for $k \geq N-1$, the $k^{th}$ excursion is superlinear for geodesics that are generic with respect to the Lebesgue measure. We use this to show that the hitting measure and the Lebesgue measure on the boundary of hyperbolic space $\mathbb{H}^N$ for any $N \geq 2$ are mutually singular.
Simultaneous Ultraviolet and X-Ray Observations of Seyfert Galaxy NGC 4151. I. Physical Conditions in the X-Ray Absorbers

We present a detailed analysis of the intrinsic X-ray absorption in the Seyfert 1 galaxy NGC 4151 using Chandra High Energy Transmission Grating Spectrometer data obtained in 2002 May as part of a program that included simultaneous ultraviolet (UV) spectra using the Hubble Space Telescope Space Telescope Imaging Spectrograph and the Far Ultraviolet Spectrographic Explorer. Previous studies, most recently using Advanced Satellite for Cosmology and Astrophysics (ASCA) spectra, revealed a large (>1022 cm-2) column of intervening gas, which has varied both in ionization state and total column density. NGC 4151 was in a relatively low flux state during the observations reported here (~25% of its historic maximum), although roughly 2.5 times as bright in the 2-10 keV band as during a Chandra observation in 2000. At both epochs, the soft X-ray band was dominated by emission lines, which show no discernible variation in flux between the two observations. The 2002 Chandra data show the presence of a very highly ionized absorber, in the form of H-like and He-like Mg, Si, and S lines, as well as lower ionization gas via the presence of inner-shell absorption lines from lower ionization species of these elements. The latter accounts for both the bulk of the soft X-ray absorption and the high covering factor UV absorption lines of O VI, C IV, and N V with outflow velocities ≈500 km s-1. The presence of high-ionization gas, which is not easily detected at low resolution (e.g., with ASCA), appears common among Seyfert galaxies. Since this gas is too highly ionized to be radiatively accelerated in sources such as NGC 4151, which is radiating at a small fraction of its Eddington Luminosity, it may be key to understanding the dynamics of mass outflow. We find that the deeper broadband absorption detected in the 2000 Chandra data is the result of both (1) lower ionization of the intervening gas due to the lower ionizing flux and (2) a factor of ~3 higher column density of the lower ionization component. To account for this bulk motion, we estimate that this component must have a velocity ≳1250 km s-1 transverse to our line of sight. This is consistent with the rotational velocity of gas arising from the putative accretion disk. While both thermal wind and magnetohydrodynamic models predict large nonradial motions, we suggest that the latter mechanism is more consistent with the results of the photoionization models of the absorbers
Renal pathology, glomerular number and volume in a West African urban community.

BACKGROUND Low glomerular number and large glomerular volume are hypothesized to be risk factors for hypertensive renal disease in adult life. Reports of human glomerular number are based on studies from developed nations and have found single kidney mean values of approximately 900 000 per kidney with a roughly 8-fold range matched by a similar range in glomerular volume. Glomerular number and volume have never been investigated in people from a developing country. METHODS This study analysed the pathology of 81 autopsy kidneys from Dakar, Senegal, and determined total glomerular number and mean glomerular volume in 28 of these kidneys using the physical disector/fractionator method. RESULTS Total glomerular number ranged 2.6-fold from 536 171 to 1 394 010, with a mean of 925 485 nephrons. The mean glomerular volume was 5.74 microm(3) x 10(6) with a 2.5-fold variation that was strongly and inversely correlated with total glomerular number. Glomerular number was inversely correlated with age, and age-associated increases in arteriosclerosis, cortical fibrosis and glomerulosclerosis were observed. Arteriolar nephrosclerosis was observed in 34% of adults. Mean glomerular number in this Dakar population was similar to that previously reported for people from developed nations, while the range of glomerular number and mean glomerular volume was much narrower. CONCLUSIONS The frequency of arteriolar nephrosclerosis in these Senegalese adults was high (34%), suggesting that hypertensive kidney disease could contribute to a large burden of future chronic kidney disease in this population. Unusually low glomerular number or large glomerular volume do not appear to provide a basis for this potential burden of kidney disease.
Bud structure, position and fate generate various branching patterns along shoots of closely related Rosaceae species: a review

Branching in temperate plants is closely linked to bud fates, either floral or vegetative. Here, we review how the fate of meristematic tissues contained in buds and their position along a shoot imprint specific branching patterns which differ among species. Through examples chosen in closely related species in different genera of the Rosaceae family, a panorama of patterns is apparent. Patterns depend on whether vegetative and floral buds are borne individually or together in mixed buds, develop as the shoot grows or after a rest period, and are located in axillary or terminal positions along the parent shoot. The resulting branching patterns are conserved among varieties in a given species but progressively change with the parent shoot length during plant ontogeny. They can also be modulated by agronomic and environmental conditions. The existence of various organizations in the topology and fate of meristematic tissues and their appendages in closely related species questions the between-species conservation of physiological and molecular mechanisms leading to bud outgrowth vs. quiescence and to floral induction vs. vegetative development.
The Role of Microglia in Prion Diseases: A Paradigm of Functional Diversity

Inflammation is a major component of neurodegenerative diseases. Microglia are the innate immune cells in the central nervous system (CNS). In the healthy brain, microglia contribute to tissue homeostasis and regulation of synaptic plasticity. Under disease conditions, they play a key role in the development and maintenance of the neuroinflammatory response, by showing enhanced proliferation and activation. Prion diseases are progressive chronic neurodegenerative disorders associated with the accumulation of the scrapie prion protein PrPSc, a misfolded conformer of the cellular prion protein PrPC. This review article provides the current knowledge on the role of microglia in the pathogenesis of prion disease. A large body of evidence shows that microglia can trigger neurotoxic pathways contributing to progressive degeneration. Yet, microglia are also crucial for controlling inflammatory, repair and regenerative processes. This dual role of microglia is regulated by multiple pathways and evidences the ability of these cells to polarize into distinct phenotypes with characteristic functions. The awareness that the neuroinflammatory response is inextricably involved in producing tissue damage as well as repair in neurodegenerative disorders, opens new perspectives for the modulation of the immune system. A better understanding of this complex process will be essential for developing effective therapies for neurodegenerative diseases, in order to improve the quality of life of patients and mitigating the personal, economic and social consequences derived from these diseases.
B-Raf(V600E) cooperates with alternative spliced Rac1b to sustain colorectal cancer cell survival.

BACKGROUND & AIMS In colorectal tumors, activating BRAF mutations occur alternative to KRAS oncogenic mutations, but in cell culture possess a much lower transforming capacity. Rac1b, a hyperactive Rac1 spliced variant, is over expressed in some colorectal tumors and activates the transcription factor nuclear factor-kappaB, which initiates a transcriptional response that promotes cell cycle progression and inhibits apoptosis. The aim of this study was to determine whether Rac1b overexpression is associated with B-Raf(V600E) in primary colorectal tumors and whether a functional cooperation between these 2 proteins exists in colorectal cells with a wild-type KRAS genotype. METHODS Screening of BRAF and KRAS mutations by direct sequencing and Rac1b mRNA expression analysis by quantitative real-time polymerase chain reaction were conducted in 74 samples (13 normal colonic mucosa, 45 primary colorectal tumors, and 16 colorectal cancer [CRC] cell lines). RNA interference and focus formation assays were used to assess the cooperation between Rac1b and B-Raf(V600E) in cancer cell viability. RESULTS Rac1b overexpression and B-Raf(V600E) are significantly associated in primary colorectal tumors (P = .008) and colorectal cell lines. The simultaneous suppression of both proteins dramatically decreased CRC cell viability through impaired cell-cycle progression and increased apoptosis. CONCLUSIONS Our data demonstrate that Rac1b and B-Raf(V600E) functionally cooperate to sustain colorectal cell viability and suggest they constitute an alternative survival pathway to oncogenic K-Ras. These results reveal a novel molecular characteristic of colon tumors containing B-Raf mutations and should help in defining novel targets for cancer therapy.
Motor skill depends on knowledge of facts

Those in 20th century philosophy, psychology, and neuroscience who have discussed the nature of skilled action have, for the most part, accepted the view that being skilled at an activity is independent of knowing facts about that activity, i.e., that skill is independent of knowledge of facts. In this paper we question this view of motor skill. We begin by situating the notion of skill in historical and philosophical context. We use the discussion to explain and motivate the view that motor skill depends upon knowledge of facts. This conclusion seemingly contradicts well-known results in cognitive science. It is natural, on the face of it, to take the case of H.M. , the seminal case in cognitive neuroscience that led to the discovery of different memory systems, as providing powerful evidence for the independence of knowledge and skill acquisition. After all, H.M. seems to show that motor learning is retained even when previous knowledge about the activity has been lost. Improvements in skill generally require increased precision of selected actions, which we call motor acuity. Motor acuity may indeed not require propositional knowledge and has direct parallels with perceptual acuity. We argue, however, that reflection on the specifics of H.M. 's case, as well as other research on the nature of skill, indicates that learning to become skilled at a motor task, for example tennis, depends also on knowledge-based selection of the right actions. Thus skilled activity requires both acuity and knowledge, with both increasing with practice. The moral of our discussion ranges beyond debates about motor skill; we argue that it undermines any attempt to draw a distinction between practical and theoretical activities. While we will reject the independence of skill and knowledge, our discussion leaves open several different possible relations between knowledge and skill. Deciding between them is a task to be resolved by future research.
Journal of Translational Medicine Adoptively Transferred Human Lung Tumor Specific Cytotoxic T Cells Can Control Autologous Tumor Growth and Shape Tumor Phenotype in a Scid Mouse Xenograft Model

Background: The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs), has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed.
The Contribution of IT to the Bottom Line: A Contingency Perspective of Strategic Dimensions

The relationship between infoonation technology and business performance has been a focus of IS research in rccent years. However. few soUd results have been found as of yet which empirieally link them together. Sorne problems rcmain with the definition and measurement of rr. organizational perfonnance and "fit" between technology and ocganizational strategy. Thus stronger empirical evidence is required be(ore concluding with ccrtainty thal IT can lead to grea1er business perfonnance. ln view ofthis, an empirical study was conducted among 126 business fums to validate a research modellinking strategic orientation and strategie rr managementto performance. Using both a perceptual (growth and profitability) and an objecti ve masure of performance (RDA), this study provides new and interesting empirical evidence (or the strategie conditions under whieh information technology contributes to the bouom line. The main thrUst of the findings is that peak perfonnance is achieved by figns that combine a strong strategie orientationwith a strategically oriented rr management.
Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex

Employing 7H11 agar medium at pH 6.6, the MICs of clarithromycin for 50% (MIC50) and 90% (MIC90) of 19 strains of Mycobacterium avium complex were 8 and 16 micrograms/ml, respectively. However, the MICs were 2 to 3 log2 dilutions lower in the 7H11 medium adjusted to pH 7.4, and the MICs on 10% OADC (oleic acid-albumin-dextrose-catalase)-enriched Mueller-Hinton agar at pH 7.3 were also 2 log2 dilutions lower than those measured on 7H11 agar at pH 6.6. Therefore, clarithromycin is more active at a physiologic than at an acidic pH.
A Putative ABC Transporter Permease Is Necessary for Resistance to Acidified Nitrite and EDTA in Pseudomonas aeruginosa under Aerobic and Anaerobic Planktonic and Biofilm Conditions

Pseudomonas aeruginosa (PA) is an important airway pathogen of cystic fibrosis and chronic obstructive disease patients. Multiply drug resistant PA is becoming increasing prevalent and new strategies are needed to combat such insidious organisms. We have previously shown that a mucoid, mucA22 mutant PA is exquisitely sensitive to acidified nitrite (A-NO2−, pH 6.5) at concentrations that are well tolerated in humans. Here, we used a transposon mutagenesis approach to identify PA mutants that are hypersensitive to A-NO2−. Among greater than 10,000 mutants screened, we focused on PA4455, in which the transposon was found to disrupt the production of a putative cytoplasmic membrane-spanning ABC transporter permease. The PA4455 mutant was not only highly sensitive to A-NO2−, but also the membrane perturbing agent, EDTA and the antibiotics doxycycline, tigecycline, colistin, and chloramphenicol, respectively. Treatment of bacteria with A-NO2− plus EDTA, however, had the most dramatic and synergistic effect, with virtually all bacteria killed by 10 mM A-NO2−, and EDTA (1 mM, aerobic, anaerobic). Most importantly, the PA4455 mutant was also sensitive to A-NO2− in biofilms. A-NO2− sensitivity and an anaerobic growth defect was also noted in two mutants (rmlC and wbpM) that are defective in B-band LPS synthesis, potentially indicating a membrane defect in the PA4455 mutant. Finally, this study describes a gene, PA4455, that when mutated, allows for dramatic sensitivity to the potential therapeutic agent, A-NO2− as well as EDTA. Furthermore, the synergy between the two compounds could offer future benefits against antibiotic resistant PA strains.
Pervasive Healthcare as a Scientific Discipline

Summary Objective: The OECD countries are facing a set of core challenges; an increasing elderly population; increasing number of chronic and lifestyle-related diseases; expanding scope of what medicine can do; and increasing lack of medical professionals. Pervasive healthcare asks how pervasive computing technology can be designed to meet these challenges. The objective of this paper is to discuss ‘pervasive healthcare’ as a research field and tries to establish how novel and distinct it is, compared to related work within biomedical engineering, medical informatics, and ubiquitous computing. Methods: The paper presents the research questions, approach, technologies, and methods of pervasive healthcare and discusses these in comparison to those of other related scientific disciplines. Results: A set of central research themes are presented; monitoring and body sensor networks; pervasive assistive technologies; pervasive computing for hospitals; and preventive and persuasive technologies. Two projects illustrate the kind of research being done in pervasive healthcare. The first project is targeted at home-based monitoring of hypertension; the second project is designing context-aware technologies for hospitals. Both projects approach the healthcare challenges in a new way, apply a new type of research method, and come up with new kinds of technological solutions. ‘Clinical proof-of-concept’ is recommended as a new method for pervasive healthcare research; the method helps design and test pervasive healthcare technologies, and in ascertaining their clinical potential before large-scale clinical tests are needed. Conclusion: The paper concludes that pervasive healthcare as a research field and agenda is novel; it is addressing new emerging research questions, represents a novel approach, designs new types of technologies, and applies a new kind of research method.