Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Application of a Physiologically-Based Pharmacokinetic Model to Predict the Pharmacokinetics of Therapeutic Proteins from Full-term Neonates to Adolescents

Physiologically-based pharmacokinetic (PBPK) modelling provides an integrated framework to predict the disposition of small molecule drugs in children and is increasingly being used for dose recommendation and optimal design of paediatric studies and in regulatory submissions. Existing paediatric PBPK models can be adopted to describe the disposition of therapeutic proteins (TPs) in children by incorporating information on age-related changes of additional physiological and biological parameters (e.g. endogenous IgG, neonatal Fc receptor, lymph flow). In this study, physiological parameters were collated from literature and evaluated for any age-dependent trends. The age-dependent physiological parameters were used to construct a paediatric PBPK model for TPs. The model was then used to predict the pharmacokinetics of recombinant human erythropoietin (EPO), infliximab, etanercept, basiliximab, anakinra and enfuvirtide in paediatric subjects. The developed paediatric PBPK model predicted the drug concentration-time profiles reasonably well in full-term neonates (clinical PK data only available for EPO), infants, children and adolescents with the ratios of predicted over observed clearance values within 1.5-fold and 25 out of 26 clearance predictions were within 0.8- to 1.25-fold of the observed values. The clinically reported data are required to further assess the predictive accuracy of PK for Fc-containing proteins in term-born children younger than 2 months. This study demonstrates the ability of PBPK models accounting for age-dependent changes in relevant parameters to predict the pharmacokinetics of different types of TPs in paediatrics. The information gained from the PBPK models described here can facilitate our understanding of the complexities of TPs’ disposition during growth and development.
LONG‐DISTANCE SEED DISPERSAL BY TAPIRS INCREASES SEED SURVIVAL AND AGGREGATES TROPICAL TREES

The dominant models explaining tree species diversity and distribution pat- terns in tropical forests are the Janzen-Connell and Recruitment Limitation models, neither of which considers the effect of long-distance seed dispersal on seed survival, seedling establishment, or the aggregated distributions of trees empirically observed at mesoscales in tropical forests. At a neotropical forest site (Maracai Island Ecological Reserve, Roraima, Brazil), we experimentally reproduced long-distance clumped seed dispersal by tapirs for the palm Maximiliana maripa. Such dispersal protects seeds from attack by species-specific bruchid beetles by (1) covering them in protective fecal material and (2) placing them in sites distant from conspecific adult tree aggregations, where beetles are less active. En- docarps distant from parent patches survived bruchid attack at a significantly higher rate than those in parent patches, as did in-feces endocarps compared to clean endocarps. A significant interaction effect between distance from patches and feces treatment showed that feces conferred protection to seeds within a parent patch but did not appear to confer additional protection to seeds already protected by distance from the parent patch. A me- soscale map compiled from aerial photography, satellite imagery, and air- and ground- truthing revealed an aggregated pattern of M. maripa palms associated with tapir latrine sites, supporting the view that long-distance seed dispersal by tapirs is responsible for the generation of palm patches and potentially important in forest-savanna boundary dynamics. We conclude that seed shadows and survival rates can justifiably be studied at the scale of tree aggregations rather than at the scale of individual trees, and that long-distance seed dispersal is neither rare nor unpredictable once we understand the movements and behavior of large, mobile animals.
Differential aluminum tolerances of two barley cultivars related to organic acids in their roots

Abstract ‘Dayton’ barley is significantly more tolerant to excess Al in acid soils and nutrient solutions than is ‘Kearney’ barley; however, the physiological or biochemical mechanisms of such differential tolerance have not been clearly established. One hypothesis is that Al‐tolerant plants contain and exude organic acids or other ligands that form stable chelates with Al and thereby reduce its chemical activity and toxicity. The objective of our study was to determine the effects of Al on concentrations of organic acids in the roots of Al‐tolerant Dayton and Al‐sensitive Kearney barley cultivars. Plants were grown for 17 days in nutrient solutions containing 0, 55 and 110 μM Al (initial pH 4.5), and their roots were analyzed for organic acids by high performance liquid chromatography. Aluminum stress significantly reduced concentrations of citric, succinic and total organic acids in the roots of Al‐sensitive Kearney barley but not in those of Al‐tolerant Dayton. Aluminum decreased concentrations of levu.
Differential Response of Liverwort (Marchantia polymorpha) Tissue to POST-Applied Quinoclamine

Abstract Quinoclamine is used in Europe, and was under evaluation in the Unites States for the control of liverwort in nursery crops. Liverwort is a nonvascular, chlorophyll-containing plant that can be problematic in greenhouse and nursery crops. POST-applied quinoclamine controls liverwort. However, liverwort structures vary in their sensitivity to POST-applied quinoclamine. Specifically, archegonial receptacles (female) are much more tolerant of quinoclamine than either antheridial receptacles (male) or thalli (leaflike structures). A series of studies were conducted to, first, document the degree of differential sensitivity between tissues to quinoclamine, and second, to determine the basis of this differential sensitivity. The dose that results in 50% of the population being controlled (I50) of antheridial receptacles and juvenile thalli were estimated to be 1.60 and 1.27 kg·ha−1, respectively. The I50 of archegonial receptacles could not be estimated, but exceeded 10.45 kg·ha−1. Chlorophyll content varied between liverwort tissues, but the content did not correlate to quinoclamine sensitivity. Absorption of 14C after application of radiolabeled quinoclamine was less in archegonial receptacles than in either antheridial receptacles or thalli. Scanning electron microscopy of the surface of the liverwort tissues revealed that archegonial receptacles had smaller pores (equivalent to stomata in higher plants) than either antheridial receptacles or thalli. The tolerance of archegonial receptacles to quinoclamine can be partially, but not exclusively, attributed to reduced absorption. This reduced absorption may be attributed to the limited pore size and less total pore area of the archegonial receptacles. Nomenclature: Liverwort, Marchantia polymorpha L. ; quinoclamine.
Treponema socranskii sp. nov., Treponema socranskii subsp. socranskii subsp. nov., Treponema socranskii subsp. buccale subsp. nov., and Treponema socranskii subsp. paredis subsp. nov. Isolated from the Human Periodontia

A new species, Treponema socranskii, and three new subspecies, T. socranskii subsp. socranskii, T. socranskii subsp. buccale, and T. socranskii subsp. paredis, which were isolated from supragingival and subgingival samples from patients with periodontitis and from patients with experimental gingivitis, are described. These organisms are treponemes that ferment carbohydrates and require rumen fluid or shortchain volatile fatty acids for growth. Fermentable carbohydrates are required as an energy source. The major products of fermentation are acetic, lactic, and succinic acids. Trace amounts of formic acid are also produced. The level of deoxyribonucleic acid-deoxyribonucleic acid homology within each subspecies is greater than 80%, whereas the level of homology between subspecies is about 60%. The average guanineplus-cytosine content of the deoxyribonucleic acid is 51 ± 1 mol%. The type strain of T. socranskii is strain ATCC 35536 (= VPI DR56BRIII6); the type strain of T. socranskii subsp. buccale is strain ATCC 35534 (= VPI D2B8); and the type strain T. socranskii subsp. paredis is strain ATCC 35535 (= VPI D46CPE1).
A COMPARISON OF ISOTOPE DILUTION AND WEIGH-SUCKLE-WEIGH METHODS FOR ESTIMATING MILK INTAKE BY PIGS

Isotope dilution estimates of milk consumption were 11.9% lower when weigh-suckle-weigh estimates were being made, suggesting that disruption of piglets and sows caused by the weigh-suckle-weigh method reduced milk consumption. Without correction for metabolic and salivary losses, the weigh-suckle-weigh method underestimated consumption. Key words: Piglet, sow, milk intake, milk production, weigh-suckle-weigh, deuterium oxide
Characteristicsof Color Visual Acuity for Normal Eyes of Young Subjects

We have developed a testing system that examines human visual performance to colors (Color Visual Acuity: CVA) at the medical practice easily and efficiently. The testing system consists of PC and LCD (Liquid Crystal Display) that is able to calibrate colors with high precision. In this paper, first we introduce our testing system and how to measure CVA using this system. Next, we discuss on the color reproduction on LCD used in our system by using high precision spectroradiometer. Then, we measure CVA for normal eyes of young subjects using 15 colors contained in NEW COLOR TEST as the basic characteristics of them. Also, we measure CVA for the same subjects by controlling the presentation time of the stimulus as the temporal characteristics of them. From the results, we can see that the CVA of “Blue-Purple” and “Green-Yellow” are noticeably lower than other colors. Also, we can see that the CVA of “Blue-Purple” affects most heavily for presentation time of stimulus.
Pseudamnicola exilis (Frauenfeld, 1863) in southern Greece: a remnant of a flock of species (Rissooidea: Hydrobiidae)?

The morphology of shell, penis, and female reproductive organs was studied in five populations of Pseudamnicola exilis (Frauenfeld) from southern Peloponnese and Kithira Island (Greece). No interpopulation differences were found in any of the characters. Thirty eight sequences of mitochondrial cytochrome oxidase subunit I (COI) and nuclear ribosomal 18S RNA genes were analysed. In COI 19 haplotypes, high haplotypy diversity, low nucleotide diversity in each population, and restricted gene flow between populations were found. NCA indicated allopatric fragmentation for all populations, and long-distance colonisation and/or past fragmentation for populations 4 and 5. Mismatch distribution in the most polymorphic population 4 reflected a bottleneck followed by population growth. The values of K2P interpopulation distances, though relatively low, pointed to congeneric distinct species within the Rissooidea. The monophyly of Pseudamnicola/Adrioinsulana clade was confirmed. Most probably the studied populations of Pseudamnicola were part of a flock of vicariant species little differentiated in morphology and ecology, many of which must have disappeared due to human impact.
Sertindole improves both the positive and negative symptoms of schizophrenia: Results of a phase III trial

OBJECTS: This large multicentre, double-blind, randomized study was designed to evaluate four doses of sertindole and haloperidol 10 mg in the treatment of patients with DSM-III-R schizophrenia. METHOD: 617 patients were randomized, of whom 595 were included in an intention-to-treat analysis. 375 patients completed the study. Patients were randomized to receive sertindole 8 mg/day, sertindole 16 mg/day, sertindole 20 mg/day, sertindole 24 mg/day or haloperidol 10 mg/day for 56days. Efficacy was assessed through the changes in score on the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions (CGI) scale. Improvement in all end-points was observed for all treatment groups. RESULTS: Sertindole 16 mg showed significantly greater efficacy against negative symptoms than haloperidol 10 mg. The optimal dose of sertindole was 16 mg/day. Sertindole 8 mg appeared to be suboptimal with respect to efficacy, and increasing the dose of sertindole above 20 mg did not appear to offer any additional benefit. Sertindole at all doses caused significantly fewer extrapyramidal symptoms than haloperidol. CONCLUSION: Sertindole is effective against positive and negative symptoms of schizophrenia within the dose range 12-24 mg daily, with an optimal starting dose of 16 mg daily. Efficacy is comparable to 10 mg of haloperidol with no difference in the time course of treatment response. The dose response relationship for efficacy with sertindole seems to plateau at about 16 mg daily with no demonstrable difference in increasing doses above this point. (Int J Psych Clin Pract 2000; 4:55-62)
Mutation screening in the human ε‐globin gene using single‐strand conformation polymorphism analysis

The human ε‐globin gene is necessary for primitive human erythropoiesis in the yolk sac. Herein we report a non‐radioactive single‐strand conformation polymorphism (SSCP) approach to screen the human ε‐globin gene and its regulatory regions for possible mutations and single‐nucleotide polymorphisms in normal adult subjects, in order to determine those genomic regions, which are not necessary for its proper regulation and function. We identified no sequence variations apart from the expected 5′ε /HincII polymorphism in the fragments analyzed, suggesting that genomic alterations in the ε‐globin gene are most likely incompatible with normal erythropoiesis and proper embryonic development. Am. J. Hematol. 81:136–138, 2006. © 2006 Wiley‐Liss, Inc.
The survival value of countershading with wild birds as predators

Experiments were carried out on garden lawns in England in which four types of green pastry prey were exposed to predation by wild birds. The prey were dark green, light green, countershaded (dark green above, light green below) and reverse shaded (i.e. identical to countershaded but laid out upside-down). Birds took significantly fewer countershaded prey than any of the other types thereby demonstrating the survival value of countershading.
Using Self-Report and Speed to Screen for Gait Limitations

The purpose of this study was to describe the point prevalence of gait limitations among elderly women participating in community health screenings. Ninety-six community-dwelling women (mean age = 75.2 years) participated. Individuals were considered to have limitations if: (1) they self-reported their health limiting them when walking “a block,” “several blocks,” or “more than one mile,” or (2) their speed over 7.62 meters was below 1.22 meters/second. More elders were identified with limitations by self-report (n = 54) than by gait speed (n = 36). Using both methods, 66 elders (68.8%) were noted to have gait limitations. Interestingly, there was poor agreement (kappa = .152) between self-report and gait speed as indicators of gait limitations. Thirty women who reported walking limitations did not appear limited by virtue of the speed test and 12 women who reported no limitations did not surpass the speed criterion. If nonobvious limitations are to be identified in women attending health screenings, both self-report and measured speed may be better than either indicator alone.
Sympathetic Nervous System Overactivity in Hypertensive Patients with Chronic Renal Failure - Role of Upright Body Position

Objective: The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys. Material and Methods: Plasma NE, ANP, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls ( n = 9) and hypertensive patients with reduced GFR ( n = 11). The same parameters were compared between healthy controls ( n = 6) and hypertensive patients with reduced GFR ( n = 6) in upright and supine positions. Results: Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 - 0.4 vs 2.1 - 0.2 nmol/l ( p < 0.001) and 13.5 - 2.1 vs 6.9 - 1.0 nmol/l ( p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 - 0.3 vs 1.7 - 0.3 nmol/l) ( p < 0.01) and patients (3.8 - 0.4 vs 2.6 - 0.4) ( p < 0.01). Supine ANP increased in controls (5.5 - 1.0 vs 8.3 - 1.1) ( p < 0.01) but not in patients (14.3 - 3.8 vs 16.1 - 3.8 nmol/l) ( p > 0.10). Plasma NE correlated positively with MAP ( p < 0.001) and negatively with GFR ( p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright ( p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright ( p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 - 0.02 vs 0.24 - 0.02) ( p < 0.05). Conclusion: Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients, and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.
OZONE EXPOSURE AND THE PRODUCTION OF REACTIVE OXYGEN SPECIES BY BRONCHOALVEOLAR CELLS IN HUMANS

Exposure to ozone injures respiratory epithelium, and the mechanisms may involve the generation of reactive oxygen species (ROS). This study tested the hypothesis that ozone exposure increases the airway burden of ROS to a greater degree in smokers than nonsmokers, and that this effect is independent of ozone-induced changes in spirometry. Healthy subjects were selected as either responders (decrement in FEV1 > 15%) or non responders (decrement in FEV1 < 5%) to ozone; each underwent 2 exposures to ozone and 1 to air, with bronchoalveolar lavage (BAL) performed 30 min (early) and 18 h (late) after exposure. Release of superoxide anion (O2-) was used as a measure of ROS release by all BAL cells, and flow cytometry was used to detect ROS production in alveolar macrophages (AM) only. Recovery of AM was approximately threefold greater in smokers than nonsmokers. Unstimulated, but not stimulated, cells obtained by BAL from smokers released approximately twofold greater amounts of O2- than cells from non smokers, both early and late after ozone exposure (p = .012 and p = .046, respectively). Stimulated, but not unstimulated, ROS generation by AM from smokers increased following ozone exposure, but the ozone effect was not significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p
The effects of dietary fibre, lactose and antibiotic on the levels of skatole and indole in faeces and subcutaneous fat in growing pigs

The effects on the production of indoles of dietary fibre, lactose and antibiotic were examined in a factorial design using 16 crossbred pigs (eight boars and eight gilts) from 40 to 90 kg live weight. The control diet was based on wheat and soya-bean meal which was partially replaced either by sugar-beet pulp (400 mg/g) or lactose (25 mg/g) or both. All diets were offered with or without the antibiotic tylosin phosphate (200 mg/kg diet). Animals were penned individually and the diet restricted to provide 1·3 M] digestible energy per kg M 0·75 . All faeces were collected for two 4-day periods at about 60 and 75 kg live weight. Animals were slaughtered on completion of the experiment and subcutaneous fat was sampled. Faeces and carcass fat were analysed for skatole and indole. There were no significant effects of treatments on growth rate but killing-out proportion was reduced ( P P P
Stress Incontinence Observed with Real Time Sonography and Dynamic Fastscan Magnetic Resonance Imaging - Insights into Pathophysiology

Our concepts of pathophysiology of stress urinary continence have been greatly shaped by developments in radiographic imaging. Simple radiographs with and without contrast initially revealed the importance of urethral descent in pathogenesis. More recently, magnetic resonance imaging (MRI) and real time ultrasonography are showing soft tissue detail within both a global pelvic and a local urethral context. Careful examination of these studies can extend our concepts of pathophysiology and lead us beyond existing paradigms. We propose a unified theory of stress incontinence based on our dynamic fastscan MRI and real time ultrasonograms of stress incontinence, incorporating known details of pelvic anatomy, sphincteric location and function. The hypothesis introduces the concept of a continence threshold at which the urethra is subjected simultaneously to both shearing and explusive forces. If these forces are sufficient to overcome urethral coaptation at threshold, leakage results. The model proposes an anatomical sequence of changes through which the incontinent urethra cycles between periods of rest and increased abdominal pressure, and suggests a way in which repeated episodes of prolpase and urethral traction by shearing forces exerted by the vagina on the urethra may contribute to the development of intrinsic sphincteric deficiency.
Migrating moths collected in tower-mounted light traps in northern New South Wales, Australia: influence of local and synoptic weather

Abstract Catches of moths in tower-mounted light traps in northern New South Wales were analysed in relation to local and synoptic weather. Catches were correlated with windspeed, relative humidity and possibly rainfall. No correlations were obtained with temperature or moon phase. Catches were more likely to occur when winds were from the east, and were associated with wind shifts. There was a significant association with the passage of depressions or troughs, but not cold fronts. The traps were considered to be poor indicators of migration associated with fronts, because these were accompanied by high winds in which trap efficiency was reduced. Stepwise multiple regressions using temperature, relative humidity, rainfall and windspeed accounted for only about 25% of the variance, much lower than in comparable studies with ground level light traps. These results are thought to indicate that the trap catches were reflecting long-distance migration, which was usually associated with disturbed weather. Back tracking with upper wind data was used to define probable sources of moths. In the spring and early summer, these sources were predominantly to the north and west of the traps, in semi-arid pastoral and subhumid cropping zones. In the late summer and autumn they were predominantly to the south and east, in the humid pastoral and forest zone. These results are discussed in relation to the migratory strategies of several important agricultural pest species.