Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of Bolivian mucosal leishmaniasis with miltefosine.

BACKGROUND Although mucosal leishmaniasis is a prominent disease, it has been studied only to a limited extent. It is classically treated with parenteral antimony or, as a last resort, amphotericin B. METHODS We treated Bolivian mucosal leishmaniasis due to Leishmania braziliensis with the oral agent miltefosine, 2.5 mg/kg/day for 28 days, and followed-up for 12 months. RESULTS Seventy-two patients were evaluable. The cure rate for the 36 patients who had "mild" disease (i.e., affecting nasal skin and nasal mucosa) was 83%. The cure rate for the 36 patients who had more extensive disease (involving the palate, pharynx, and larynx) was 58%. Patients refused to be randomized to parenteral agents, but the cure rate for an almost contemporary group who was receiving amphotericin B (45 mg/kg over 90 days) was 7 (50%) of 14. CONCLUSIONS In this unrandomized trial, oral miltefosine was at least as effective as heroic doses of parenteral amphotericin B. The cure rate for miltefosine was approximately equivalent to historical cure rates using parenteral pentavalent antimony for mild and extensive disease in neighboring Peru. Although gastrointestinal side reactions do occur with miltefosine, its toxicity profile is superior to that of antimony and far superior to that of amphotericin B--in part because of the inherent attractiveness of oral versus parenteral agents. Our results suggest that miltefosine should be the treatment of choice for mucosal disease in North and South America.
The GNSS Reflectometry response to the ocean surface

We investigate the Global Navigation Satellite System Reflectometry (GNSS-R) measurements collected by the Space GNSS Receiver-Remote Sensing Instrument (SGR-ReSI) on board the TechDemoSat-1 (TDS-1) satellite. The sensitivity of the SGR-ReSI measurements to the ocean surface winds and waves are characterized. The effects of sea surface temperature, wind direction, and rain are also investigated. The SGR-ReSI measurements exhibited sensitivity through the entire range of wind speeds sampled in this dataset, up to 35 m/s. A significant dependence on the larger waves was observed for winds <; 6 m/s. Additionally, an interesting dependence on SST was observed where the slope of the SGR-ReSI measurements is positive for winds <; 5 m/s and reverses for winds > 5 m/s. There appeared to be very little wind direction signal, and investigation of the rain impacts found no apparent sensitivity in the data. These results are shown through the analysis of global statistics and examination of a few case studies. This released SGR-ReSI dataset provided the first opportunity to comprehensively investigate the sensitivity of satellite-based GNSS-R measurements to various ocean surface parameters. The upcoming NASA's Cyclone Global Navigation Satellite System (CYGNSS) satellite constellation will utilize a similar receiver to SGI-ReSI and thus this data provides valuable pre-launch knowledge.
Energy optimization based path selection algorithm for IEEE 802.11s Wireless Mesh Networks

It is everyone's dream to have network connectivity anywhere at all times. This dream can only be realized provided there are feasible solutions that are put in place for the next generation of wireless works. Wireless Mesh Networks (WMNs) configures itself and because of its cost effectiveness, it is therefore seen as a solution for the next generation networks. However, this field still has a lot of limitations and the main constrain is that the energy of the nodes is very limited, especially when the network is deployed in rural areas where electricity is a scares resource. This research therefore presents an energy optimization based path selection algorithm for IEEE 802.11s WMNs which is aimed at addressing the above mentioned constrains. As a newly proposed standard specifically designed for WMN, the IEEE 802.11s does not consider energy conservation as a priority in its protocol. As a result, the main goal for this research is that paths with enough energy for transmission in the network must be selected when transmitting packets. Our simulation results obtained from the experiments prove that there is a substantial increase with regard to the network's operational time when energy is considered by the protocol used in IEEE 802.11s.
The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature.

OBJECTIVE Infantile Pompe's disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies. METHODS A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included in the study. Information on clinical history, physical examination, and diagnostic parameters was collected. RESULTS The course of Pompe's disease is essentially the same in the Dutch and the general patient population. Symptoms start at a median age of 1.6 months in both groups. The median age of death is 7.7 and 6 months, respectively. Five percent of the Dutch patients and 8% of all reported patients survive beyond 1 year of age. Only 2 patients from literature became older than 18 months. A progressive cardiac hypertrophy is characteristic for infantile Pompe's disease. The diastolic thickness of the left ventricular posterior wall and cardiac weight at autopsy increase significantly with age. Motor development is severely delayed and major developmental milestones are generally not achieved. For the Dutch patient group, growth deviates significantly from normal despite start of nasogastric tube feeding. Levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, or creatine kinase-myocardial band isoenzyme are typically elevated, although aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase increase significantly with age. The patients have fully deleterious mutations. Acid alpha-glucosidase activity is severely deficient. CONCLUSIONS Survival, decrease of the diastolic thickness of the left ventricular posterior wall, and achievement of major motor milestones are valid endpoints for therapeutic studies of infantile Pompe's disease. Mutation analysis and measurement of the alpha-glucosidase activity should be part of the enrollment program.
The Effect of Left-Sided Versus Right-Sided Contrast Infusion on Attenuation of the Main Pulmonary Artery When Performing Computed Tomography Angiograms of the Chest

Objective: This study assesses if the arm of contrast infusion influences attenuation of the main pulmonary artery in computed tomography (CT) angiograms to evaluate for pulmonary emboli. Methods: Four hundred seven consecutive CT angiograms performed to exclude pulmonary emboli were reviewed. Patient characteristics, study details, and interpretation results were collected. After exclusion criteria, 100 studies from each scanner (4, 16, and 64 slice) remained. A reader, blinded to injection side, measured the attenuation of the main pulmonary artery. Results: The average attenuation in the main pulmonary artery was similar if infused through the right (275.4 HU) or left (275.0 HU) arm when controlling for confounders with a multiple regression analysis (P = 0.82). There was no statistical difference (P > 0.05) in the number of scans with attenuation less than 250 (45.9% right, 42.9% left), 200 (25.3% right, 29.2% left), or 150 HU (11.6% right, 12.3% left) and interpreted as indeterminate (1.4% right, 3.9% left) or nondiagnostic (2.7% right, 2.6% left). Conclusions: Main pulmonary artery attenuation is independent of the arm of infusion when evaluating mean attenuation, attenuation beneath 250, 200, or 150 HU, or indeterminate or nondiagnostic interpretations for patients undergoing CT angiograms of the chest to rule out pulmonary emboli.
Auxotrophic Mutations Reduce Tolerance of Saccharomyces cerevisiae to Very High Levels of Ethanol Stress

ABSTRACT Very high ethanol tolerance is a distinctive trait of the yeast Saccharomyces cerevisiae with notable ecological and industrial importance. Although many genes have been shown to be required for moderate ethanol tolerance (i.e., 6 to 12%) in laboratory strains, little is known of the much higher ethanol tolerance (i.e., 16 to 20%) in natural and industrial strains. We have analyzed the genetic basis of very high ethanol tolerance in a Brazilian bioethanol production strain by genetic mapping with laboratory strains containing artificially inserted oligonucleotide markers. The first locus contained the ura3Δ0 mutation of the laboratory strain as the causative mutation. Analysis of other auxotrophies also revealed significant linkage for LYS2, LEU2, HIS3, and MET15. Tolerance to only very high ethanol concentrations was reduced by auxotrophies, while the effect was reversed at lower concentrations. Evaluation of other stress conditions showed that the link with auxotrophy is dependent on the type of stress and the type of auxotrophy. When the concentration of the auxotrophic nutrient is close to that limiting growth, more stress factors can inhibit growth of an auxotrophic strain. We show that very high ethanol concentrations inhibit the uptake of leucine more than that of uracil, but the 500-fold-lower uracil uptake activity may explain the strong linkage between uracil auxotrophy and ethanol sensitivity compared to leucine auxotrophy. Since very high concentrations of ethanol inhibit the uptake of auxotrophic nutrients, the active uptake of scarce nutrients may be a major limiting factor for growth under conditions of ethanol stress.
Sulfation of Chondroitin Sulfate in Human Articular Cartilage

The chondroitin ABC lyase digestion products of normal human femoral condyle articular cartilage and of purified aggrecan were analyzed for their mono- and nonsulfated disaccharide composition. Changes in the total tissue chemistry were most pronounced during the period from birth to 20 years of age, when the -[GlcAβ,3GalNAc6]- disaccharide content increased from approximately 50% to 85% of the total disaccharide content and there was a concomitant decrease in the content of the 4-sulfated disaccharide. In general, the disaccharide content of the deeper layers of immature cartilage were richer in the 4-sulfated residue than the upper regions of the tissue. As the tissue aged and decreased in thickness, the disaccharide composition became more evenly 6-sulfated. The newly synthesized chondroitin sulfate chains had a similar composition to the endogenous chains and also underwent the same age and zonal changes. The monoclonal antisera 3B3(+) and 2B6(+) were used to immunolocalize the unsaturated 6- and 4-sulfated residues generated at the reducing termini of the chondroitin sulfate chains by digestion with chondroitin ABC lyase, and these analyses indicated that the sulfation pattern at this position did not necessarily reflect the internal disaccharide composition of the chains. In summary, the sulfation pattern of chondroitin sulfate disaccharides from human normal articular cartilage varies with the age of the specimen, the position (topography) on the joint surface, and the zone of cartilage analyzed. Furthermore, these changes in composition are a consequence of both extracellular, post-translational processing of the core protein of aggrecan and changes in the sulfotransferase activity of the chondrocyte.
Increased Endothelial Exocytosis and Generation of Endothelin-1 Contributes to Constriction of Aged Arteries

Rationale: Circulating levels of endothelin (ET)-1 and endogenous ETA-mediated constriction are increased in human aging. The mechanisms responsible are not known. Objective: Investigate the storage, release, and activity of ET-1 system in arteries from young and aged Fischer-344 rats. Methods and Results: After NO synthase inhibition (L-NAME), thrombin contracted aged arteries, which was inhibited by endothelial denudation, ETA receptor antagonism (BQ123), and ECE inhibition (phosphoramidon, SM19712) or by inhibiting exocytosis (TAT-NSF, N-ethylmaleimide-sensitive factor inhibitor). Thrombin did not cause endothelium-dependent contraction of young arteries. In aged but not young arteries, thrombin rapidly increased ET-1 release, which was abolished by endothelium denudation or TAT-NSF. L-NAME did not affect ET-1 release. ET-1 immunofluorescent staining was punctate and distinct from von Willebrand factor (VWF). VWF and ET-1 immunofluorescent intensity was similar in young and aged quiescent arteries. Thrombin rapidly increased ET-1 staining and decreased VWF staining in aged but had no effect in young aortas. After L-NAME, thrombin decreased VWF staining in young aortas. NO donor DEA-NONOate (1 to 100 nmol/L) reversed thrombin-induced exocytosis in young (VWF) but not aged L-NAME–treated aortas (VWF, ET-1). Expression of preproET-1 mRNA and ECE-1 mRNA were increased in aged compared to young endothelium. BigET-1 levels and contraction to exogenous BigET-1 (but not ET-1) were also increased in aged compared to young arteries. Conclusions: The stimulated exocytotic release of ET-1 is dramatically increased in aged endothelium. This reflects increased reactivity of exocytosis, increased expression and storage of ET-1 precursor peptides, and increased expression of ECE-1. Altered endothelial exocytosis of ET-1 and other mediators may contribute to cardiovascular pathology in aging.
Identification of HHR23A as a Substrate for E6-associated Protein-mediated Ubiquitination*

The human papilloma virus E6-associated protein (E6AP) functions as a ubiquitin protein ligase (E3) in the E6-mediated ubiquitination of p53. E6AP is also an E3 in the absence of E6, but its normal cellular substrates have not yet been identified. Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. HHR23A binds E6AP and is ubiquitinated in vitro in an E6AP-dependent manner. Ubiquitinated forms of endogenous HHR23A are detectable in mammalian cells. Overexpression of wild-type E6AP in vivo enhances the ubiquitination of HHR23A, whereas a dominant negative E6AP mutant inhibits HHR23A ubiquitination. Although HHR23A is a stable protein in non-synchronized cells, its levels are regulated in a cell cycle-dependent manner, with specific degradation occurring during S phase. The S phase degradation of HHR23A could be blocked in vivo by dominant negative E6AP, providing direct evidence for the involvement of E6AP in the regulation of HHR23A. Consistent with a role of the HHR23 proteins in DNA repair, UV-induced DNA damage inhibited HHR23A degradation. Although the precise role of HHR23 proteins in DNA repair and cell cycle progression remains to be elucidated, our data suggest that E6AP-mediated ubiquitination of HHR23A may have important implications in DNA repair and cell cycle progression.
Effect of Chloramphenicol on Denitrification in Flexibacter canadensis and "Pseudomonas denitrificans"

It was recently reported that chloramphenicol inhibits existing denitrification enzyme activity in sediments and carbon-starved cultures of "Pseudomonas denitrificans. " Therefore, we studied the effect of chloramphenicol on denitrification by Flexibacter canadensis and "P. denitrificans. " Production of N(inf2)O from nitrate by F. canadensis cells decreased as the concentration of chloramphenicol was increased, and 10.0 mM chloramphenicol completely inhibited N(inf2)O production. "P. denitrificans" was less sensitive to chloramphenicol, and production of N(inf2)O from nitrate was inhibited by only about 50% even in the presence of 10.0 mM chloramphenicol. These results suggested that inhibition of denitrification enzyme activity depended on the concentration of chloramphenicol. Increasing the concentration of chloramphenicol decreased the rate of production of nitrite from nitrate by F. canadensis cells, and the concentration of chloramphenicol which resulted in 50% inhibition of production of nitrite from nitrate was 2.5 mM. In contrast, the rates of production of nitrite from nitrate by intact cells and cell extracts of "P. denitrificans" were inhibited by only 58 and 54%, respectively, at a chloramphenicol concentration of 10.0 mM. Chloramphenicol caused accumulation of NO from nitrite but not from nitrate and inhibited NO consumption in F. canadensis; however, it had neither effect in "P. denitrificans. " Chloramphenicol did not affect N(inf2)O consumption by these organisms. We concluded that chloramphenicol inhibits denitrification at the level of nitrate reduction and, in F. canadensis, also at the level of NO reduction.
Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure

Abstract Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in patients with cancer. The aim of this study was to identify early predictors of death in patients with cancer admitted to the ICU for ARF who were not intubated at admission. We conducted analysis of a prospective randomized controlled trial including 219 patients with cancer with ARF in which day-28 mortality was a secondary endpoint. Mortality at day 28 was 31.1%. By multivariate analysis, independent predictors of day-28 mortality were: age (odds ratio [OR] 1.30/10 years, 95% confidence interval [CI] [1.01–1.68], p = 0.04), more than one line of chemotherapy (OR 2.14, 95% CI [1.08–4.21], p = 0.03), time between respiratory symptoms onset and ICU admission > 2 days (OR 2.50, 95% CI [1.25–5.02], p = 0.01), oxygen flow at admission (OR 1.07/L, 95% CI [1.00–1.14], p = 0.04) and extra-respiratory symptoms (OR 2.84, 95%CI [1.30–6.21], p = 0.01). After adjustment for the logistic organ dysfunction (LOD) score at admission, only time between respiratory symptoms onset and ICU admission > 2 days and LOD score were independently associated with day-28 mortality. Determinants of death include both factors non-amenable to change, and delay in ARF management. These results suggest that early intensive care management of patients with cancer with ARF may translate to better survival.
Differential Ca2+‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions

N‐ and P/Q‐type voltage dependent calcium channels (VDCCs) mediate transmitter release at neonatal rat neuromuscular junction (NMJ). Thus the neonatal NMJ allows an examination of the coupling of different subtypes of VDCCs to the release process at a single synapse. We studied calcium dependence of transmitter release mediated by each channel by blocking with ω‐conotoxin GVIA the N‐type channel or with ω‐agatoxin IVA the P/Q‐type channel while changing the extracellular calcium concentration ([Ca2+]o). Transmitter release mediated by P/Q‐type VDCCs showed steeper calcium dependence than N‐type mediated release (average slope 3.6 ± 0.09 vs. 2.6 ± 0.03, respectively). Loading the nerve terminals with 10 µm BAPTA‐AM in the extracellular solution reduced transmitter release and occluded the blocking effect of ω‐conotoxin GVIA (blockade −2 ± 9%) without affecting the action of ω‐agatoxin IVA (blockade 85 ± 4%). Both VDCC blockers were able to reduce the amount of facilitation produced by double‐pulse stimulation. In these conditions facilitation was restored by increasing [Ca2+]o. The facilitation index (fi) was also reduced by loading nerve terminals with 10 µm BAPTA‐AM (fi = 1.2 ± 0.1). The control fi was 2.5 ± 0.1. These results show that P/Q‐type VDCCs were more efficiently coupled to neurotransmitter release than were N‐type VDCCs at the neonatal neuromuscular junction. This difference could be accounted for by a differential location of these channels at the release site. In addition, our results indicate that space–time overlapping of calcium domains was required for facilitation.
Influence of different resistance traits on the competitive growth of Haemophilus influenzae in antibiotic-free medium and selection of resistant populations by different {beta}-lactams: an in vitro pharmacodynamic approach.

OBJECTIVES The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains. METHODS Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one beta-lactamase-negative (beta(-); 0.015, 1 and 1), one beta-lactamase-positive (beta(+); 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one beta(-) ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one beta(+) amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu.h/mL) were calculated and differences between values in antibiotic-free (AUBC(K)) and in antibiotic simulations determined (ABBC(0-24) = AUBC(K0-24)-AUBC(0-24)). RESULTS In antibiotic-free medium, total population increased by 1.7 log(10) cfu/mL from 0 to 24 h: final composition approximately 90% beta(-), approximately 6.5% beta(+), approximately 2.5% BLNAR and approximately 1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by beta(+) after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC(0-24) was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus approximately 33), beta(+) (77.8 versus approximately 52), BLNAR (66.1 versus 18.6-30.4) or BLPACR (40.8 versus approximately 0). CONCLUSIONS Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against beta-lactamase-producing strains and those carrying ftsI gene mutations.
A mathematical model for long range expansion planning of generation and transmission in electric utility systems

This paper provides a mathematical model (linear mixed integer program) for the problem of selecting an expansion plan over a planning horizon for an electric utility system. The objective function that is chosen is the minimization of the net present value of the capital investment cost associated with the construction of power plants and transmission lines plus the operating costs of the system. The restrictions associated with the problem are the requirement to satisfy the forecasted demands of the systems for electrical energy plus the physical restrictions that result from having limited capital resources and plant site limitations. The model provides construction expansion schedules for power plants and transmission lines (i.e. what capacity to build, where the additional capacity is to be located, and when it is to be completed). Additionally, an approximate operating schedule for plants and transmission lines is provided. An application of the modeling technique to a regional electrical utility system illustrating the formulation methods and the results that can be obtained is given.