Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of lipid nanoparticles to ocular drug delivery

ABSTRACT Introduction: Although eye drops are widely used as drug delivery systems for the anterior segment of the eye, they are also associated with poor drug bioavailability due to transient contact time and rapid washout by tearing. Moreover, effective drug delivery to the posterior segment of the eye is challenging, and alternative routes of administration (periocular and intravitreal) are generally needed, the blood–retinal barrier being the major obstacle to systemic drug delivery. Areas covered: Nanotechnology, and especially lipid nanoparticles, can improve the therapeutic efficiency, compliance and safety of ocular drugs, administered via different routes, to both the anterior and posterior segment of the eye. This review highlights the main ocular barriers to drug delivery, as well as the most common eye diseases suitable for pharmacological treatment in which lipid nanoparticles have proved efficacious as alternative delivery systems. Expert opinion: Lipid-based nanocarriers are among the most biocompatible and versatile means for ocular delivery. Mucoadhesion with consequent increase in pre-corneal retention time, and enhanced permeation due to cellular uptake by corneal epithelial cells, are the essential goals for topical lipid nanoparticle delivery. Gene delivery to the retina has shown very promising results after intravitreal administration of lipid nanoparticles as non-viral vectors.
NATURAL SELECTION IN POPULATIONS SUBJECT TO A MIGRATION LOAD

Abstract Migration tends to oppose the effects of divergent natural selection among populations. Numerous theoretical and empirical studies have demonstrated that this migration–selection balance constrains genetic divergence among populations. In contrast, relatively few studies have examined immigration's effects on fitness and natural selection within recipient populations. By constraining local adaptation, migration can lead to reduced fitness, known as a “migration load,” which in turn causes persistent natural selection. We develop a simple two-island model of migration–selection balance that, although very general, also reflects the natural history of Timema cristinae walking-stick insects that inhabit two host plant species that favor different cryptic color patterns. We derive theoretical predictions about how migration rates affect the level of maladaptation within populations (measured as the frequency of less-cryptic color-pattern morphs), which in turn determines the selection differential (the within-generation morph frequency change). Using data on color morph frequencies from 25 natural populations, we confirm previous results showing that maladaptation is higher in populations receiving more immigrants. We then present novel evidence that this increased maladaptation leads to larger selection differentials, consistent with our model. Our results provide comparative evidence that immigration elevates the variance in fitness, which in turn leads to larger selection differentials, consistent with Fisher's Theorem of Natural Selection. However, we also find evidence that recurrent adult migration between parapatric populations may tend to obscure the effects of selection.
Effect of wheat content, fat source and enzyme supplementation on diet metabolisability and broiler performance

1. A 3 × 3 × 2 factorial experiment studied the interactions of fat source (tallow, soya, tallow:soya [2:1] blend), wheat level (700, 350, 0 g/kg) and enzyme inclusion (Avizyme 1300, absent, present) in diets for broilers fed ad libitum in individual cages from 7 to 35d. Bird performance, fat digestibility, viscosity of ileal contents and diet metabolisability (AME) were measured. 2. There were no significant effects of fat source on bird performance. However, there was a significant effect on fat digestibility, which was highest for soya and lowest for tallow. Diet AME content was also significantly affected by fat source and reflected differences in fat digestibility. 3. Dry matter (DM) intake, liveweight gain (LWG) and gain:food were all reduced at 700 g wheat/kg. Viscosity of ileal contents increased with increasing wheat inclusion. 4. There were no significant effects of enzyme on DM intake or LWG but gain:food was improved by 2%. Diet AME content was increased with enzyme addition, the effect being greatest (9%) with tallow at 700 g wheat/kg. 5. Viscosity of ileal contents was reduced and fat digestibility increased with enzyme addition and there were significant wheat enzyme interactions attributable to no differences with zero wheat but marked responses to enzyme at 700 g wheat/kg. 6. The results confirm important interactions between wheat content and fat composition in relation to fat digestibility, AME content and food efficiency.
Efectividade de exercícios de estabilidade em adultos com dor cervical crónica: Revisão sistemática

As patologias musculo esqueleticas sao as mais comuns e aquelas que apresentam maiores custos para a Saude Publica tanto na America do Norte como na Europa (Punnett & Wegman, 2004). Em particular, a Dor Cervical Cronica encontra-se englobada neste grupo de patologias e a sua incidencia tem vindo a aumentar de forma significativa nas duas ultimas decadas (Hakala, Rimpela, Salminen, Virtanen, & Rimpela, 2002), situando-se logo atras da Dor Lombar como a mais comum das patologias deste foro (Ferrari & Russell, 2003; Ihlebaek, Brage, & Eriksen, 2007). A sua origem exacta e raramente identificada no exame clinico ou nos exames complementares de diagnostico (Siivola, Levoska, Tervonen, Ilkko, Vanharanta, & Keinanen-Kiukaanniemi, 2002; Peterson, Bolton, ABSTRACT
Nontemplate Polymerization of Free Nucleotides Into Genetic Elements by Thermophilic DNA Polymerase in vitro

DNA synthesis is the cornerstone of all life forms and is required to replicate and restore the genetic information. Usually, DNA synthesis is carried out only by DNA polymerases semiconservatively to copy preexisting DNA templates. We report here that DNA strands were synthesized ab initio in the absence of any DNA or RNA template by thermophilic DNA polymerases at (a) a constant high temperature (74°C), (b) alternating temperatures (94°C/60°C/74°C), or (c) physiological temperatures (37°C). The majority of the ab initio synthesized DNA represented short sequence blocks, repeated sequences, intergenic spacers, and other unknown genetic elements. These results suggest that novel DNA elements could be synthesized in the absence of a nucleic acid template by thermophilic DNA polymerases in vitro. Biogenesis of genetic information by thermophilic DNA polymerase-mediated nontemplate DNA synthesis may explain the origin of genetic information and could serve as a new way of biosynthesis of genetic information that may have facilitated the evolution of life. Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides, and Nucleic Acids to view the free supplemental file.
The Effect of Age on the Corneal Subbasal Nerve Plexus

Purpose: To measure subbasal nerve density and orientation in normal human corneas across a broad age range. Methods: Sixty-five normal corneas of 65 subjects were examined by using tandem scanning confocal microscopy. Ages of subjects ranged from 15 to 79 years (mean 46 ± 19 years), with 5 subjects from each hemidecade. Subbasal nerve fiber bundles appeared as bright, well-defined linear structures in confocal images of the central cornea. Images from 3 to 8 scans per eye (mean 4.6 ± 1.8 scans) were randomly presented to a masked observer for analysis. The mean subbasal nerve density (total nerve length [μm] within a confocal image [area = 0.166 mm2]), the mean nerve number per confocal scan, and the mean nerve orientation were determined by using a custom software program. Correlations between age and nerve density and age and nerve orientation were assessed by using Pearson correlation coefficients. Results: The subbasal nerve plexus was visible in the central cornea of all subjects. The mean subbasal nerve density was 8404 ± 2012 μm/mm2 (range 4735 to 14,018 μm/mm2). The mean subbasal nerve number was 4.6 ± 1.6 nerves (range 1 to 8 nerves). The mean subbasal nerve orientation was 94 ± 16 degrees (range 58 to 146 degrees). There was no correlation between age and subbasal nerve density (r = 0.21, P = 0.09) or between age and subbasal nerve orientation (r = −0.19, P = 0.12). Conclusion: The density and orientation of the subbasal nerve plexus in the central human cornea does not change with age.
A new family of Marx generator based on resonant converter

This paper presents a novel topology to generate high voltage with utilization of slow and fast power switches. New concepts used in this topology include numbers of diode-capacitor units in parallel with resonant circuits which are connected to a positive buck-boost converter. The resonant circuit reverses the voltage polarity of the capacitors. This configuration has capability of generating a flexible high voltage with certain number of capacitors. The advantage of this topology is to use slow switches, less number of diodes and capacitors compare to Marx generator. Simulations have been performed to verify the proposed topology.
Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study

Background: Triple therapy is recommended for Helicobacter pylori eradication, yet consensus on the duration of treatment is lacking. Aim: To compare the efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and clarithromycin in a large, multicentre, double-blind and randomised study. Methods: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled in 81 endoscopy units in Italy, were randomised to receive omeprazole, amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by histological examination and carbon-13 urea breath test 4 weeks after treatment. Results: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n = 661) analyses showed no significant differences between the eradication rates of OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p = 0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave significantly higher eradication rates compared with omeprazole and amoxicillin treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%, 17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and amoxicillin (p = 0.11). Conclusions: 1-week and 2-week triple treatments for H pylori eradication are similar in terms of efficacy, safety and patient compliance.
Survival attributable to an exposure

In the survival analysis context, when an intervention either reduces a harmful exposure or introduces a beneficial treatment, it seems useful to quantify the gain in survival attributable to the intervention as an alternative to the reduction in risk. To accomplish this we introduce two new concepts, the attributable survival and attributable survival time, and study their properties. Our analysis includes comparison with the attributable risk function as well as hazard‐based alternatives. We also extend the setting to the case where the intervention takes place at discrete points in time, and may either eliminate exposure or introduce a beneficial treatment in only a proportion of the available group. This generalization accommodates the more realistic situation where the treatment or exposure is dynamic. We apply these methods to assess the effect of introducing highly active antiretroviral therapy for the treatment of clinical AIDS at the population level. Copyright © 2009 John Wiley & Sons, Ltd.
Disability on Irish Farms—A Real Concern

ABSTRACT Farmers operate within hazardous environments while conducting their day-to-day tasks, potentially resulting in injury or disability. Disability can serve as a major life-changing event for the farmer, the farm family, and the farm business. In Ireland, the agricultural sector reported the highest incidence of disability, yet there is relatively little known on the impact of agricultural-based disability. In 2007, a questionnaire was appended to the Teagasc (Irish Agricultural and Food Development Authority) National Farm Survey to obtain some metric of the prevalence and impact of disability on Irish farms, in addition to quantifying service/support requirements of farm operators experiencing disability. Almost 5.9% (∼6611) of Irish farm operators reported disability, primarily caused through illness/disease. Arthritis (31.4%), back problems (17%), and heart circulatory problems (12.5%) were most frequently reported. The lowest prevalence of disability was found among tillage (1.4%) and dairy (4.1%) farms, with the highest prevalence among cattle farms (7.1%). Family farm income was lower on disability-experiencing farms relative to nondisability farms (€123 per hectare), with a lower participation in off-farm employment also identified. Many farm operators (∼20%) ceased off-farm employment following disability. Discontinuation of off-farm employment can further precipitate family farm income decline, but also place additional pressures on the farm business if quality services/supports are not available. The current provision of services/supports to farm operators experiencing disability is perceived largely insufficient across the entire service/support spectrum from when disability was first experienced through to retirement. Awareness and issues surrounding eligibility were the primary reasons for failing to avail of currently available service/supports.
High-frequency modulated secondary-side self-powered isolated gate driver for full range PWM operation of SiC power MOSFETs

The present work proposes a solution for an isolated gate driver suitable for SiC MOSFETs. The driver is implemented by means of two small magnetic transformers, to provide the turn-on and turn-off gate signals, as well as the power required for an adequate gate control. The operation is based on the modulation of the PWM pulses with a high frequency (HF) square-waveform signal. The resulting modulated AC waveform is applied to the primary side of the first transformer, and reconstructed at the secondary side to obtain the gate driving signal. Simultaneously, the HF modulating signal is connected to the primary of the second transformer, to provide the required gate drive voltage levels and power at the secondary side, ensuring full range duty ratio operation. Given that both primary side signals are HF symmetrical waveforms, saturation is avoided at both transformers, for any duty ratio operation. Therefore, the proposed solution provides galvanic isolation for power and gate signal transfer with very small core sizes, allowing for an overall size reduction vs. conventional solutions. This enables much more compact designs, which are critical in high-power density applications and multilevel converters. After describing the basic operation, experimental results on a prototype are shown, thus demonstrating the feasibility of the proposed solution.
Design and implementation of an omnidirectional mobile robot platform with unified I/O interfaces

Nowadays, mobile robots have been investigated in many scenarios. Among varieties of mobile robots, their I/O interfaces varies a lot, which seriously hinders the popularity of mobile robots. A practical and versatile mobile robot platform is needed both in academic research and industrial applies. In this paper, we designed a low-cost omnidirectional mobile robot platform, named Savvy. Savvy is equipped with a variety of unified I/O interfaces and multifunctional. The software system framework of this platform is built based on ROS. We extended a number of functions for Savvy and carried out four experiments, including motion calibration, SLAM, autonomous navigation and pedestrian following. The results verified that Savvy is adaptive to indoor environment with high positioning precision, which can be employed in logistics and various HRI applications.
Physiological Parameters in the Blood of a Murine Stress-Induced Depression Model before and after Repeated Passive Exercise

Background Animal models are necessary to study the mechanism underlying the effects of exercise on depression but an effective procedure for exercise treatment and exercise effects on physiological parameters in a specific depression model need to be characterized. Methods Physiological parameters including lactate, partial pressue of O2 (pO2) and CO2 (pCO2) saturated O2 (sO2), pH, HCO3, total CO2 (TCO2), and base excess extracellular fluid (BEecf) levels in the blood were measured after treatment with passive exercise in normal mice and a stress-induced depression model. Results Normal mice or mice that were subjected to daily 2-hour restraint for 14 days (2 hours×14 days of restraint) were placed on a running wheel that was rotating at a speed of 9 m/min for 1 hour per day for 1 to 21 days. After repeated exercise in mice that were previously subjected to 2 hours×14 days restraint, plasma lactate levels decreased, the levels of pO2, sO2, and pH tended to increase, and the levels of pCO2 decreased in the absence of significant changes in HCO3, TCO2, and BEecf. However, none of these changes were additive to the stress effects or were much more severe than those induced after repeated passive exercise in normal mice. Conclusion These results suggest that passive exercise for 1 hour daily for 14 to 21 consecutive days on a running wheel rotating at a speed of 9 m/min may be used as an exercise protocol without inducing severe additive effects on physiological burdens.
Whole body protein turnover in chronically undernourished individuals.

1. Two groups of adult men were studied in Bangalore, India, under identical conditions: the 'normal weight' subjects (mean body mass index 20.8 kg/m2) were medical students of the institute with access to habitual energy and protein intakes ad libitum. The other group, designated 'undernourished', were labourers on daily wages (mean body mass index 16.7 kg/m2). 2. In an earlier study we obtained lower absolute values for both basal metabolic rate and protein synthesis in the undernourished subjects; however, when the data were expressed on a body weight or fat-free mass basis, a trend towards higher rates of protein synthesis, as well as higher basal metabolic rate, was evident. The suggestion was made that such results reflected the relatively higher energy intakes per kg body weight of the undernourished subjects on the day of study. The objective of the present study was therefore to control for the dietary intake during the measurement of whole body protein turnover. 3. In the present study dietary intakes were equated on a body weight basis; however, expressed per kg fat-free mass, the normal weight subjects had received marginally higher intakes of energy and protein. The results, however, were similar to those of the previous study. In absolute terms, basal metabolic rate, protein synthesis and breakdown were lower in the undernourished subjects. When expressed per kg body weight or per kg fat-free mass, the undernourished subjects had higher basal metabolic rates than the well-nourished subjects, whereas no differences were seen in the rate of protein synthesis or breakdown. (ABSTRACT TRUNCATED AT 250 WORDS)
ADMINISTRATION OF RECOMBINANT INTERLEUKIN-11 IMPROVES THE HEMODYNAMIC FUNCTIONS AND DECREASES THIRD SPACE FLUID LOSS IN A PORCINE MODEL OF HEMORRHAGIC SHOCK AND RESUSCITATION

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 μg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 μg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 ± 7.5 mmHg, 71.0 ± 8.9 mmHg, and 72.9 ± 12.3 mmHg, respectively) than in group III (59.9 ± 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 ± 0.56 L/min) than in group III (2.99 ± 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 ± 325 mL and 1.0035, 82 ± 21 mL) than in group III (958 ± 390 mL and 1.0053, 125 ± 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This strategy also significantly reduced the extent of third space fluid losses while also having a favorable impact on the intravascular volume status as evidenced by the improved urine output.
Effect of the acute and chronic administration of the selective 5‐HT6 receptor antagonist SB‐271046 on the activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study

This study examined the effect of the acute and repeated per os (p.o.) administration of the selective 5‐HT6 receptor antagonist SB‐271046, on the number, as well as the firing pattern of spontaneously active dopamine (DA) neurons in the rat substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized male Sprague‐Dawley rats. This was accomplished using the technique of extracellular in vivo electrophysiology. A single p.o. administration of either 1, 3, or 10 mg/kg of SB‐271046 did not significantly alter the number of spontaneously active SNC DA neurons per stereotaxic electrode tract compared to vehicle‐treated animals. The acute administration of either 1 or 3 mg/kg of SB‐271046 did not significantly alter the number of spontaneously active VTA DA neurons. In contrast, a significant decrease in the number of spontaneously active VTA DA neurons was observed after a single administration of 10 mg/kg of SB‐271046 compared to vehicle‐treated animals. The acute p.o. administration of SB‐271046 significantly altered the firing pattern parameters of all (bursting + nonbursting DA neurons) DA neurons, particularly those in the VTA, compared to vehicle‐treated animals. The repeated p.o. administration (once per day for 21 days) of 1, 3, or 10 mg/kg of SB‐271046 did not significantly alter the number of spontaneously active VTA DA neurons compared to vehicle‐treated animals. The repeated administration of 3 or 10 mg/kg of SB‐271046 significantly increased the number of spontaneously active SNC DA neurons compared to vehicle controls. Overall, the repeated administration of SB‐271046 had relatively little effect on the firing pattern of midbrain DA neurons. The results obtained following the chronic administration of SB‐271046 show that this compound has a profile different from that of typical or atypical antipsychotic drugs in this model. Clinical studies are required to understand what role 5‐HT6 receptor blockade might eventually play in the treatment of schizophrenia. Synapse 52:20–28, 2004. © 2004 Wiley‐Liss, Inc.