Miracle-dz/UniFAR-FTUs huggingface dataset:
Inherent ageing in humans: the case for studying master athletes

Ageing is a process that can be considered inherent, universal, progressive and decremental (Strehler, 1962). It results in the erosion of physiological function and the eventual outcome is death. Here we suggest that when applied to humans, the term ‘‘ageing,’’ as commonly used, concatenates the effects of more than one process, thereby confounding the interpretation of the many human ageing studies that have been performed. Whether they be crosssectional (of which there are a number) or longitudinal (of which there are fewer), there are likely to be many confounding factors to these studies. These include nutritional, environmental and socioeconomic factors. However, even allowing for these factors, we suggest that disuse or physical inactivity is the most overlooked and possibly the most significant, even in otherwise ‘‘healthy’’ populations. Disuse here is defined not in the context of complete inactivity (such as bed rest or immobilization) but in the evolutionary context of levels of activity that are below that required, or expected based, on our genetic inheritance (Booth et al., 2002). To probe the inherent ageing process requires a diametrically different approach to that associated with geriatric medicine. This is because inherent ageing is a fundamental process common to all animal biology and is not a pathological complication. For measured decrements in function to be genuinely attributed to ageing they must not be the result of pathologies that may arise from these confounding factors. Master athletes not only provide an interesting population of study for the exercise physiologist but may also provide the best model for understanding the fundamental human ageing process, as they remain essentially free from these confounding factors, most notably, disuse.
SAW analogs of Brewster's angles: the dependence on the strip shape

The analogs of Brewster's angles for surface acoustic waves (SAW) were discovered by one of the authors (S.V.B.) thirty years ago. Considering the reflection of classical Rayleigh wave in the isotropic half-space at oblique incidence by long topographic irregularities of small thickness like projections and grooves it was found by perturbation method that the reflection coefficient is equal to zero for some angle of incidence. With Poisson's ratio changing from 0 to 0.5 the angle changes within a narrow range from 25.91 0 to 28.53 0 independently from the shape of irregularities. The problem was never treated more accurately then by the first order perturbation method on a small parameter as the thickness/wavelength ratio. In this work, the impedance method is used for a correct investigation of the problem in the case of periodic strips. A strong dependence of the angle value on a small parameter, if the last is more than 0.03, is observed. Moreover, a second such angle appears and both angles become closer and disappear for thick projections. The practically important cases of the aluminum strips on piezoelectric STX- quartz and of 128 0 YX-LiNbO3 crystals are also considered.
Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet‐activating factor and N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine

Lipoxins are trihydroxytetraene metabolites derived through a double lipoxygenation of arachidonic acid. Lipoxin A4 (LXA4) was prepared by total chemical synthesis, and its capacity to modulate eosinophil migration has been evaluated. LXA4 is a weak and partial chemotactic agent; at 10−6 M, it achieved about 20% of the response of 10−6 M platelet‐activating factor (PAF). Preincubation of eosinophils with increasing doses of LXA4 (10−10−10−5 M) resulted in a concentration‐dependent inhibition of cell migration induced by 10‐6 M formyl‐methionyl‐leucyl‐phenylalanine (FMLP) and 10‐6 M PAF. The concentration of LXA4 which produced 50% inhibition (IC50) of eosinophil migration was approximately 10‐6 M. LXA4 (10‐10‐10‐6 M) did not elicit ECP release or modulate ECP release induced by 10‐6 M FMLP. LXA4 may have antiallergic properties in preventing eosinophilic migration.
Unpacking the Effect of Parental Monitoring on Early Adolescent Problem Behavior

This study explores the monitoring process longitudinally among a sample of rural early adolescents and addresses two research questions: (a) Does maternal knowledge mediate the relationship between three aspects of the parental monitoring process and adolescent problem behavior: active parent monitoring efforts, youth disclosure, and parental supervision? (b) Are these meditational pathways moderated by the affective quality of the parent–child relationship? Parent efforts to monitor youth and youth disclosure in the Fall of Grade 6 predicted substance use and delinquency in Grade 8. These relations were mediated by increases in maternal knowledge assessed in the Spring of Grade 6, suggesting that the protective effects of these constructs are partially indirect. Supervision was not significantly related to maternal knowledge or problem behavior. Parent efforts to monitor were more strongly related to maternal knowledge in families with high levels of positive affect than in families with low levels of positive affect.
Localization of basic proteins in human myelin

The myelin basic protein (MBPs) represent a family of proteins (charge isomers) which account for 35% of the total myelin protein. Localization studies have been inconclusive because MBP is not a single protein. Antibodies obtained by injection of MBP into animals recognized all members of the MBP family. In the studies reported here, we have fractionated the MBPs into specific components or charge isomers. One of these which contains citrulline accounts for about 20% of the total MBP. We report the localization of this single MBP to the intraperiod line of myelin by immunoelectron microscopy. For these studies several specific antibodies were used including antibodies raised against total MBP, specific MBP peptides, and against a tetracitrulline peptide. This latter antibody was specific for component 8 (C‐8) of MBP. Since C‐8 is the only MBP which contains citrulline it was used to localize this particular form of MBP principally to the intraperiod line by immunogold electron microscopy, while antibody against total MBP (consisting of all charge isomers C‐1→C‐8) labelled both the major dense line and the intraperiod line. When the anti‐citrulline antibody was used with a 3 nm gold conjugated Fab fragments prepared from the secondary antibody, 66.5% of the gold particles were localized to the intraperiod line, while 11.2% of gold particles were localized to the major dense line. On the other hand, with the monoclonal anti‐MBP antibodies reactive with residues 69–74, 59.4% of the gold particles were localized to the major dense line and 23.6% of gold particles at the intraperiod line. Other supporting evidence includes increased labelling of myelin by 125I labelled anti‐citrulline IgG when isolated myelin was swollen, a process known to take place at the intraperiod line. Gold particles were demonstrated at the intraperiod line in swollen and recompacted myelin. C‐8 was shown to associate preferentially with lipids asymmetrically localized to the intraperiod line. © 1993 Wiley‐Liss, Inc.
A Protein (ORF2) Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Interacts with Notch1 and Notch3

ABSTRACT Like other A lphaherpesvirinae subfamily members, bovine herpesvirus 1 (BHV-1) establishes latency in sensory neurons. The latency-related RNA (LR-RNA) is abundantly expressed in latently infected sensory neurons. An LR mutant virus with stop codons at the amino terminus of the first open reading frame (ORF) in the LR gene (ORF2) does not reactivate from latency, in part because it induces higher levels of apoptosis in infected neurons. ORF2 is not the only viral product expressed during latency, but it is important for the latency reactivation cycle because it inhibits apoptosis. In this study, a yeast 2-hybrid screen revealed that ORF2 interacted with two cellular transcription factors, Notch1 and Notch3. These interactions were confirmed in mouse neuroblastoma cells by confocal microscopy and in an in vitro “pulldown” assay. During reactivation from latency, Notch3 RNA levels in trigeminal ganglia were higher than those during latency, suggesting that Notch family members promote reactivation from latency or that reactivation promotes Notch expression. A plasmid expressing the Notch1 intercellular domain (ICD) stimulated productive infection and promoters that encode the viral transcription factor bICP0. The Notch3 ICD did not stimulate productive infection as efficiently as the Notch1 ICD and had no effect on bICP0 promoter activity. Plasmids expressing the Notch1 ICD or the Notch3 ICD trans-activated a late promoter encoding glycoprotein C. ORF2 reduced the trans-activation potential of Notch1 and Notch3, suggesting that ORF2 interfered with the trans-activation potential of Notch. These studies provide evidence that ORF2, in addition to inhibiting apoptosis, has the potential to promote establishment and maintenance of latency by sequestering cellular transcription factors.
Intrauterine administration of peripheral blood mononuclear cells enhances early development of the pre‐implantation bovine embryo

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) prior to bovine embryo transfer (ET) was previously shown to improve the pregnancy rate. To better understand how PBMCs improve the pregnancy rate, we examined gene expression in the cells from uterine lumen and evaluated the morphology of bovine pre‐attachment embryos in utero following intrauterine administration of PBMCs. On day 3 of the estrous cycle (day 0 = estrous), bovine PBMCs were isolated and suspended in RPMI 1640, and were incubated for 24 hr. The cultured PBMCs were administered non‐surgically to the uterine horn ipsilateral to the corpus luteum on day 4 of the estrous cycle (PBMC group). On day 9, endometrial–luminal lymphoid cells from uterine lumen ipsilateral to the corpus luteum were collected by uterine flushing. Transcripts for macrophage‐colony stimulating factor in the lymphoid cells were more abundant in the PBMC group than in the control group (P < 0.05). On day 7 (of the separate experiments), five blastocysts were each transferred to the luminal area, to which PBMCs had been administered on day 4. These embryos were allowed to develop in utero until day 15 of gestation, when embryos were non‐surgically retrieved from the uterus. The average length of trophoblasts recovered from the PBMC group was significantly longer than that of the control group (51.6 ± 7.8 vs. 27.4 ± 6.0 mm, P < 0.05). Our results strongly suggest that intrauterine administration of PBMCs improves endometrial environment, which promotes early development of pre‐attachment conceptuses. Mol. Reprod. Dev. 77:954–962, 2010. © 2010 Wiley‐Liss, Inc.
Scaling of caterpillar body properties and its biomechanical implications for the use of a hydrostatic skeleton

SUMMARY Caterpillars can increase their body mass 10,000-fold in 2 weeks. It is therefore remarkable that most caterpillars appear to maintain the same locomotion kinematics throughout their entire larval stage. This study examined how the body properties of a caterpillar might change to accommodate such dramatic changes in body load. Using Manduca sexta as a model system, we measured changes in body volume, tissue density and baseline body pressure, and the dimensions of load-bearing tissues (the cuticle and muscles) over a body mass range from milligrams to several grams. All Manduca biometrics relevant to the hydrostatic skeleton scaled allometrically but close to the isometric predictions. Body density and pressure were almost constant. We next investigated the effects of scaling on the bending stiffness of the caterpillar hydrostatic skeleton. The anisotropic non-linear mechanical response of Manduca muscles and soft cuticle has previously been quantified and modeled with constitutive equations. Using biometric data and these material laws, we constructed finite element models to simulate a hydrostatic skeleton under different conditions. The results show that increasing the internal pressure leads to a non-linear increase in bending stiffness. Increasing the body size results in a decrease in the normalized bending stiffness. Muscle activation can double this stiffness in the physiological pressure range, but thickening the cuticle or increasing the muscle area reduces the structural stiffness. These non-linear effects may dictate the effectiveness of a hydrostatic skeleton at different sizes. Given the shared anatomy and size variation in Lepidoptera larvae, these mechanical scaling constraints may implicate the diverse locomotion strategies in different species.
Phase equilibrium constraints on the viscosity of silicic

By using recently determined experimental phase equilibria we show that the viscosity of granitic magmas emplaced at upper crustal levels is approximately constant at -• 104.5 Pa s, irrespective of their temperature and level of emplacement. Magmas crystallizing as granitic plutons are not water-poor and thus not more viscous than their extrusive equivalents. Instead, comparison between pre-eruption magma viscosities of extrusive silicic-intermediate and intrusive granitic magmas shows that the former are on average slightly more viscous. Given the typical strain rates in silicic magma chambers, magma rheological behavior is expected to be dominantly Newtonian, bubbles having a minor rheological influence at depth although exceptions can exist. Thus whether a silicic-intermediate magma is erupted or frozen at depth depends primarily on the rheological properties of surrounding terranes or on external tectonic factors, but not on the rheology of the magma itself. However, preeruptive viscosities of extrusive magmas rarely exceed 106 Pa.s, which suggests that crystal-melt mushes with higher viscosities cannot leave the magma storage regions beneath volcanoes. The narrow range of viscosities displayed by silicic- intermediate magmas results from both the strong control that pressure exerts on volatile solubilities in silicate melts and thermal limitations required to produce acid magmas. Considerations of the relationships between magma crystallinities, bulk SiO2, and preeruptive melt H20 contents show that the higher the melt H20 content is the higher the maximum crystallinity that a given magma will be while still being potentially erupted. An empirical correlation is proposed that enables us to estimate preeruptive melt H:O contents of erupted magmas by knowing their crystallinity and bulk SiO:.
[Simulation model for estimating the cancer care infrastructure required by the public health system].

OBJECTIVE To develop a simulation model using public data to estimate the cancer care infrastructure required by the public health system in the state of São Paulo, Brazil. METHOD Public data from the Unified Health System database regarding cancer surgery, chemotherapy, and radiation therapy, from January 2002-January 2004, were used to estimate the number of cancer cases in the state. The percentages recorded for each therapy in the Hospital Cancer Registry of Brazil were combined with the data collected from the database to estimate the need for services. Mixture models were used to identify subgroups of cancer cases with regard to the length of time that chemotherapy and radiation therapy were required. A simulation model was used to estimate the infrastructure required taking these parameters into account. RESULTS The model indicated the need for surgery in 52.5% of the cases, radiation therapy in 42.7%, and chemotherapy in 48.5%. The mixture models identified two subgroups for radiation therapy and four subgroups for chemotherapy with regard to mean usage time for each. These parameters allowed the following estimated infrastructure needs to be made: 147 operating rooms, 2 653 operating beds, 297 chemotherapy chairs, and 102 radiation therapy devices. These estimates suggest the need for a 1.2-fold increase in the number of chemotherapy services and a 2.4-fold increase in the number of radiation therapy services when compared with the parameters currently used by the public health system. CONCLUSION A simulation model, such as the one used in the present study, permits better distribution of health care resources because it is based on specific, local needs.
Multiple facial eccrine hidrocystomas: effective topical therapy with atropine

1 Holt PJA, Davies MG, Saunders KC, Nuki G. Pyoderma gangrenosum: clinical and laboratory findings in fifteen patients with special reference to polyarthritis. Medicine 1980; 59: 114–33. 2 Olivieri I, Costa AM, Cantini F et al. Pyoderma gangrenosum in association with undifferentiated seronegative spondylarthropathy. Arthritis Rheum 1996; 39: 1062–5. 3 Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24. 4 Dougados M, van der Linden S, Juhlin R et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991; 34: 1218–27. 5 Burrows NP, Lockwood CM. Antineutrophil cytoplasmic antibodies and their relevance to the dermatologist. Br J Dermatol 1995; 132: 173–81. 6 Vignon-Pennamen MD, Zelinsky-Gurung A, Janssen F et al. Pyoderma gangrenosum with pulmonary involvement. Arch Dermatol 1989; 125: 1239–42. 7 Lebbé C, Moulonguet-Michau I, Perrin P et al. Steroid-responsive pyoderma gangrenosum with vulvar and pulmonary involvement. J Am Acad Dermatol 1992; 27: 623–5. 8 Chow RKP, Ho VC. Treatment of pyoderma gangrenosum. J Am Acad Dermatol 1996; 34: 1047–60.
Population Pharmacokinetics of Tenofovir in AIDS Patients

The interindividual variability of tenofovir pharmacokinetics in HIV+ patients is quite large, but the sources of variability are incompletely understood. Intraindividual variability has not been characterized, although it may have an impact on efficacy and therapeutic drug monitoring. The aims of the study were to estimate intraindividual variability of tenofovir clearance and to assess interactions with associated antiviral drugs. Tenofovir concentrations (median 2; range, 1–5) were measured in 175 patients during several dosing intervals. Covariates and dosing regimen of associated antiretroviral drugs were recorded prospectively. The data were analyzed by a population approach. The final model was a 2‐compartment model with first‐order absorption rate. The elimination clearance was found to be related to the ratio of body weight to serum creatinine. Among the 15 drugs coadministered, no interaction on tenofovir kinetics was significant. The global variability of CL/F, after accounting for variability to variation of body weight and serum creatinine, was about 50%, with 20% due to interindividual variability and 30% due to interoccasion variability. In a few patients, clearance (and AUC) could vary by a factor of 2 between occasions. The interoccasion variability was not related to the delay between occasions. In the context of drug monitoring, for a given patient, the dose should not be adapted unless the variation of concentration between 2 occasions is large, or the 24‐hour trough concentration at steady state is lower than 12 μg/L.
Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo.

We have compared the expression of the genes encoding transforming growth factors beta 1, beta 2 and beta 3 during mouse embryogenesis from 9.5 to 16.5 days p.c. using in situ hybridisation to cellular RNAs. Each gene has a different expression pattern, which gives some indication of possible biological function in vivo. All three genes appear to be involved in chondroossification, though each is expressed in a different cell type. Transcripts of each gene are also present in embryonic epithelia. Epithelial expression of TGF beta 1, beta 2 and beta 3 RNA is associated with regions of active morphogenesis involving epithelial-mesenchymal interactions. In addition, widespread epithelial expression of TGF beta 2 RNA can be correlated with epithelial differentiation per se. The localisation of TGF beta 2 RNA in neuronal tissue might also be correlated with differentiation. Finally both TGF beta 1 and beta 2 transcripts are seen in regions actively undergoing cardiac septation and valve formation, suggesting some interaction of these growth factors in this developmental process.
Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants*

Selenium is an essential trace element and it is well known that selenium is necessary for cell culture. However, the mechanism underlying the role of selenium in cellular proliferation and survival is still unknown. The present study using Jurkat cells showed that selenium deficiency in a serum-free medium decreased the selenium-dependent enzyme activity (glutathione peroxidases and thioredoxin reductase) within cells and cell viability. To understand the mechanism of this effect of selenium, we examined the effect of other antioxidants, which act by different mechanisms. Vitamin E, a lipid-soluble radical-scavenging antioxidant, completely blocked selenium deficiency-induced cell death, although α-tocopherol (biologically the most active form of vitamin E) could not preserve selenium-dependent enzyme activity. Other antioxidants, such as different isoforms and derivatives of vitamin E, BO-653 and deferoxamine mesylate, also exerted an inhibitory effect. However, the water-soluble antioxidants, such as ascorbic acid, N-acetyl cysteine, and glutathione, displayed no such effect. Dichlorodihydrofluorescein (DCF) assay revealed that cellular reactive oxygen species (ROS) increased before cell death, and sodium selenite and α-tocopherol inhibited ROS increase in a dose-dependent manner. The generation of lipid hydroperoxides was observed by fluorescence probe diphenyl-1-pyrenylphosphine (DPPP) and HPLC chemiluminescence only in selenium-deficient cells. These results suggest that the ROS, especially lipid hydroperoxides, are involved in the cell death caused by selenium deficiency and that selenium and vitamin E cooperate in the defense against oxidative stress upon cells by detoxifying and inhibiting the formation of lipid hydroperoxides.