Miracle-dz/UniFAR-FTUs huggingface dataset:
The Rate of Cerebral Utilization of Glucose, Ketone Bodies, and Oxygen: A Comparative in Vivo Study of Infant and Adult Rats

Extract: Cerebral blood flow (CBF) was measured by means of 141Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(l-methylpropyl)2-thio-barbituric acid. Cerebral arteriovenous differences of acetoacetate, D-β-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr.The mean CBF values of 0.48 ± 0.04 and 0.62 ± 0.07 ml/(g × min), ± SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation.At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-β-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-β-hydroxybutyrate only in infant animals.In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA × min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA × min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete oxidation of glucose and ketone bodies and expressed as micromoles per (mg DNA × min), was similar in fed and starved rats of both age groups (Table 3), indicating that ketone bodies serve as an alternative substrate for glucose during starvation. Calculated CMRO2 for glucose plus ketone bodies was similar to the measured CMRO2 in adult rats both in the fed and the starved groups. For infant rats, calculated CMRO2 for glucose plus ketone bodies was higher than measured CMRO2, indicating that in this age group a portion of substrate was used for synthesis or storage rather than for complete oxidation.Speculation: The present study supports the concept that during the period of maximum myelination in rat brain, when the need of substrate for synthesis of lipid and protein is great, the infant rat brain is adapted to a higher utilization of D-β-hydroxybutyrate and acetoacetate than later on in life. Thus, during starvation when glucose supply is limited but acetoacetate and D-β-hydroxybutyrate are available, the synthesis of myelin could be preserved.
Global Optimization: A Distributed Compensation Algorithm and its Convergence Analysis

This paper introduces a distributed compensation approach for the global optimization with separable objective functions and coupled constraints. By employing compensation variables, the global optimization problem can be solved without the information exchange of coupled constraints. The convergence analysis of the proposed algorithm is presented with the convergence condition through which a diminishing step-size with an upper bound can be determined. The convergence rate can be achieved at $O({lnT}/{\sqrt {T}})$ . Moreover, the equilibrium of this algorithm is proved to converge at the optimal solution of the global optimization problem. The effectiveness and the practicability of the proposed algorithm is demonstrated by the parameter optimization problem in smart building.
Developmental Stability and Fitness: A Review

Developmental stability reflects the ability of individuals to undergo stable development of their phenotype under a range of environmental conditions. Developmental instability is measured in terms of fluctuating asymmetry or phenodeviance. A negative relationship between developmental instability and fitness has figured as a prominent untested assumption in the literature. A review of available information from the literature on the relationship between developmental instability and various fitness components such as growth, fecundity, and longevity suggests that there indeed is a general negative relationship. Symmetrical individuals do generally have faster growth, higher fecundity, and better survival than do more asymmetrical individuals. These differences appear partially to arise from lower competitive ability and higher risks of predation and parasitism of asymmetrical individuals compared with more symmetrical conspecifics. The relationship between developmental stability and fitness may be either direct or indirect.
A newly recognized congenital myasthenic syndrome attributed to a prolonged open time of the acetylcholine‐induced ion channel

Five familial cases (in two families) and one sporadic case of a new congenital myasthenic syndrome were investigated. Symptoms arise in infancy or later life. Typically, one finds selective involvement of cervical, scapular, and finger extensor muscles, ophthalmoparesis, and variable involvement of other muscles. There is a repetitive muscle action potential to single nerve stimulus in all muscles and a decremental response at 2 to 3 Hz stimulation in clinically affected muscles. Microelectrode studies reveal markedly prolonged end‐plate potential (epp), miniature end‐plate potential (mepp), and miniature end‐plate current; normal quantum content of the epp; and a smaller than normal or low‐normal mepp amplitude. Light microscopy demonstrates predominance of type I fibers, small groups of atrophic fibers, tubular aggregates and vacuoles near end‐plates, abnormal end‐plate configuration, and nonspecific myopathic changes. Abundant acetylcholinesterase activity is present at all end‐plates, and the activity and kinetic properties of this enzyme in muscle are normal. Calcium accumulated at the end‐plate in one patient. Quantitative electron microscopy shows decrease in the size of nerve terminals, increase in the density of synaptic vesicles, and reduction in the length of postsynaptic membranes. There is focal degeneration of junctional folds with corresponding loss of acetylcholine receptor, most marked in cases with the lowest mepp amplitude. There are no immune complexes at the end‐plate. Fiber regions near end‐plates display dilation, proliferation, and degeneration of the sarcoplasmic reticulum; nuclear, mitochondrial, and myofibrillar degeneration; and vacuoles resembling those found in periodic paralysis. A prolonged open time of the acetylcholine‐induced ion channel is considered to be the basic abnormality and may account for the physiological, morphological, and clinical alterations.
Dehydroepiandrosterone replacement in women with adrenal insufficiency.

BACKGROUND The physiologic role of dehydroepiandrosterone in humans is still unclear. Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency. METHODS In a double-blind study, 24 women with adrenal insufficiency received in random order 50 mg of dehydroepiandrosterone orally each morning for four months and placebo daily for four months, with a one-month washout period. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin, and we evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment, after one and four months of treatment with dehydroepiandrosterone, after one and four months of placebo, and one month after the end of the second treatment period. RESULTS Treatment with dehydroepiandrosterone raised the initially low serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol decreased significantly. Dehydroepiandrosterone significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from base line was -0.18+/-0.29 after four months of dehydroepiandrosterone therapy, as compared with 0.03+/-0.29 after four months of placebo (P=0.02). As compared with placebo, dehydroepiandrosterone significantly increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002), and satisfaction with both mental and physical aspects of sexuality (P=0.009 and P=0.02, respectively). CONCLUSIONS Dehydroepiandrosterone improves well-being and sexuality in women with adrenal insufficiency.
Stable Association of hsp90 and p23, but Not hsp70, with Active Human Telomerase*

The ribonucleoprotein telomerase holoenzyme is minimally composed of a catalytic subunit, hTERT, and its associated template RNA component, hTR. We have previously found two additional components of the telomerase holoenzyme, the chaperones p23 and heat shock protein (hsp) 90, both of which are required for efficient telomerase assembly in vitro and in vivo. Both hsp90 and p23 bind specifically to hTERT and influence its proper assembly with the template RNA, hTR. We report here that the hsp70 chaperone also associates with hTERT in the absence of hTR and dissociates when telomerase is folded into its active state, similar to what occurs with other chaperone targets. Our data also indicate that hsp90 and p23 remain associated with functional telomerase complexes, which differs from other hsp90-folded enzymes that require only a transient hsp90·p23 binding. Our data suggest that components of the hsp90 chaperone complex, while required for telomerase assembly, remain associated with active enzyme, which may ultimately provide critical insight into the biochemical properties of telomerase assembly.
GaN HEMT devices: Experimental results on normally-on, normally-off and cascode configuration

Power electronics systems play key function in power management and motion control: power consumption and volume reduction are strongly required in new applications oriented to protect environment. Moreover, a switching frequency increase is demanded for microwave and power switching applications, thus reducing passive component and converter volume: however, increasing the switching frequency directly increases switching losses. Also, switching applications are very demanding, because semiconductor switches are required to withstand high voltage in reverse condition and handle large current in forward operation mode. New material and new devices are studied to satisfy such requirements, like SiC and GaN devices. In this work, several 600-V class GaN-on-Si HEMT prototypes are presented. These devices have been designed and developed for power switching converter applications. In order to offer a complete scenario of GaN-on-Si HEMT technology, normally-on, normally-off, and cascode-connected devices have been characterized. Achieved experimental results of static and pulsed measurements are then shown.
Angiographically defined collateral circulation and risk of stroke in patients with severe carotid artery stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group.

BACKGROUND AND PURPOSE Blood supply through collateral pathways improves regional cerebral blood flow and may protect against ischemic events. The effect of collaterals on the risk of stroke and transient ischemic attack (TIA), in the presence of angiographic severe internal carotid artery (ICA) stenosis, was assessed. METHODS Angiographic collateral filling through anterior communicating and posterior communicating arteries and retrograde filling through ophthalmic arteries were determined in all patients at entry into the North American Symptomatic Carotid Endarterectomy Trial. Kaplan-Meier event-free survival analyses were performed on 339 medically treated and 342 surgically treated patients. RESULTS The presence of collaterals supplying the symptomatic ICA increased with severity of stenosis. Two-year risk of hemispheric stroke in medically treated patients with severe ICA stenosis was reduced in the presence of collaterals: 27.8% to 11.3% (P=0.005). Similar reductions were observed for hemispheric TIA (36.1% versus 19.1%; P=0.008) and disabling or fatal strokes (13.3% versus 6.3%; P=0.11). For surgically treated patients, the perioperative risk of hemispheric stroke was 1.1% in the presence of collaterals versus 4. 9% when absent. The 2-year stroke risks for surgical patients with and without collaterals were 5.9% versus 8.4%, respectively. Neither comparison in the surgical group was statistically significant. The observed reductions were independent of the degree of ICA stenosis and other vascular risk factors. CONCLUSIONS Collaterals are associated with a lower risk of hemispheric stroke and TIA, both long term and perioperatively. Angiographic identification of collaterals assists in identifying patients with severe ICA stenosis at lower risk of stroke and TIA.
Synthesis and Antibacterial Activity of Amino Acid and Dipeptide Prodrugs of IMB-070593, a Fluoroquinolone Candidate

A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32–7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39–23.13 mg/kg) which is 1.19–1.50 fold more active than the parent drug.
EARLY ONSET NEONATAL SEPSIS IN PRETERM PREMATURE RUPTURE OF MEMBRANES

Objective: To determine the frequency of early onset neonatal sepsis in newborn with various duration of preterm premature rupture of membranes (PPROM). Study Design: Cross sectional study. Place and Duration of Study: Neonatal Intensive Care Unit Combined Military Hospital, Lahore from November 2009 to November 2010. Material and Methods: Neonates of singleton pregnancies complicated by preterm premature rupture of the membranes (PPROM) with delivery between 30 and 36 weeks gestation were included in the study. The overall frequency of neonatal sepsis was calculated on clinical and serological basis. Comparison of the frequency of sepsis among groups with varying duration of rupture of membranes was done. Results: Out of 164 babies, 84 (51.2%) were female and 80 (48.8%) were male. Mean maternal age was 23 years (range: 18-36 years). Mean gestational age was 33 weeks (range: 30-36 weeks). Sepsis was suspected in 41(25%) babies on clinical grounds. C-reactive protein was raised in 36 (22%) neonates. There was statistically insignificant difference between clinical versus serological diagnosis (p=0.515). Frequency of neonatal sepsis was significantly higher in mothers with longer duration of rupture of membrane (p < 0.001). Conclusion: Frequency of neonatal sepsis was observed to be 22%. PPROM is an important risk factor for early onset neonatal sepsis.
An interactive fuzzy satisficing method for multiobjective integer programming problems through genetic algorithms

This paper deals with multiobjective integer programming problems by considering fuzzy goals of the decision maker for objective functions. After determining the fuzzy goals of the decision maker, if the decision maker specifies the reference membership values, the corresponding Pareto optimal solution can be obtained by solving the augmented minimax problem which becomes an integer programming problem. For solving the problem, decoding algorithms for 0-1 programming problems are revised and ringed double strings are also introduced. Then an interactive fuzzy satisficing method is presented together with an illustrative numerical example.
Spatial vs. temporal effects on demographic and genetic structures: the roles of dispersal, masting and differential mortality on patterns of recruitment in Fagus sylvatica

Trees’ long lifespan, long‐distance dispersal abilities and high year‐to‐year variability in fecundity are thought to have pervasive consequences for the demographic and genetic structure of recruited seedlings. However, we still lack experimental studies quantifying the respective roles of spatial processes such as restricted seed and pollen dispersal and temporal processes such as mast seeding on patterns of regeneration. Dynamics of European beech (Fagus sylvatica) seedling recruitment was monitored in three plots from 2004 to 2006. Six polymorphic microsatellite genetic markers were used to characterize seedlings and their potential parents in a 7.2‐ha stand. These seedlings were shown to result from 12 years of recruitment, with one predominant year of seedling recruitment in 2002 and several years without significant recruitment. Using a spatially explicit mating model based on parentage assignment, short average dispersal distances for seed (δs = 10.9 m) and pollen (43.7 m < δp < 57.3 m) were found, but there was also a non‐negligible immigration rate from outside the plot (ms = 20.5%; 71.6% < mp < 77.9%). Hierarchical analyses of seedling genetic structure showed that (i) most of the genetic variation was within plots; (ii) the genetic differentiation among seedling plots was significant (FST = 2.6%) while (iii) there was no effect of year‐to‐year seed rain variation on genetic structure. In addition, no significant effect of genetic structure on mortality was detected. The consequences of these results for the prediction of population dynamics at ecological timescales are discussed.
REFLEXÕES SOBRE A LITERACIA DIGITAL DOS SENIORES AO JOGAR JOGOS DIGITAIS

O artigo apresenta uma investigacao realizada com cinco participantes da Universidade Aberta a Terceira Idade (UATI) na UNEB/Bahia, Brasil, ao jogar jogos digitais, com o proposito de observar alguns indicadores sobre a evolucao da literacia digital nos seniores. Os seniores jogaram o jogo “Guardioes da Floresta” durante duas sessoes e responderam a tres questoes sobre o que recordavam do jogo e sobre o que teriam aprendido a respeito das Tecnologias da Informacao e Comunicacao. Foi adoptada a abordagem metodologica qualitativa e a triangulacao de dados foi feita atraves da observacao direta e participante, questionario e entrevista semi-estruturada. A analise dos dados revelou que as praticas de jogos digitais pelos seniores contribuem para a sua literacia digital em que apresentam habilidades e competencias em evolucao. Estrategias e taticas sao reveladas quando estao a descobrir maneiras de jogar e solucionar problemas, criar formas de ultrapassar os desafios, construindo-se significados e elaborando novos comportamentos. Palavras-chave: Jogos digitais; Literacia; Literacia digital; Seniores
Prospects for treating osteoarthritis: enzyme–protein interactions regulating matrix metalloproteinase activity

Primary osteoarthritis (OA) is a musculoskeletal disorder of unknown etiology. OA is characterized by an imbalance between anabolism and catabolism in, and altered homeostasis of articular cartilage. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motif are upregulated in OA joints. Extracellular matrix (ECM) proteins are critical for resistance to compressive forces and for maintaining the tensile properties of the tissue. Tissue inhibitor of metalloproteinases (TIMPs) is the endogenous inhibitor of MMPs, but in OA, TIMPs do not effectively neutralize MMP activity. Upregulation of MMP gene expression occurs in OA in a milieu of proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor α. Presently, the medical therapy of OA includes mainly nonsteroidal anti-inflammatory drugs and corticosteroids which dampen pain and inflammation but appear to have little effect on restoring joint function. Experimental interventions to restore the imbalance between anabolism and catabolism include small molecule inhibitors of MMP subtypes or inhibitors of the interaction between IL-1 and its receptor. Although these agents have some positive effects on reducing MMP subtype activity they have little efficacy at the clinical level. MMP-9 is one MMP subtype implicated in the degradation of articular cartilage ECM proteins. MMP-9 was found in OA synovial fluid as a complex with neutrophil gelatinase-associated lipocalin (NGAL) which protected MMP-9 from autodegradation. Suppressing NGAL synthesis or promoting NGAL degradation may result in reducing the activity of MMP-9. We also propose initiating a search for enzyme–protein interactions to dampen other MMP subtype activity which could suppress ECM protein breakdown.
Glial and neuronal expression of polyglutamine proteins induce behavioral changes and aggregate formation in Drosophila

Patients with polyglutamine expansion diseases, like Huntington's disease or several spinocerebellar ataxias, first present with neurological symptoms that can occur in the absence of neurodegeneration. Behavioral symptoms thus appear to be caused by neuronal dysfunction, rather than cell death. Pathogenesis in polyglutamine expansion diseases is largely viewed as a cell‐autonomous process in neurons. It is likely, however, that this process is influenced by changes in glial physiology and, at least in the case of DRPLA glial inclusions and glial cell death, seems to be an important part in the pathogenesis. To investigate these aspects in a Drosophila model system, we expressed polyglutamine proteins in the adult nervous system. Glial‐specific expression of a polyglutamine (Q)‐expanded (n = 78) and also a nonexpanded (n = 27) truncated version of human ataxin‐3 led to the formation of protein aggregates and glial cell death. Behavioral changes were observed prior to cell death. This reveals that glia is susceptible to the toxic action of polyglutamine proteins. Neuronal expression of the same constructs resulted in behavioral changes similar to those resulting from glial expression but did not cause neurodegeneration. Behavioral deficits were selective and affected two analyzed fly behaviors differently. Both glial and neuronal aggregates of Q78 and Q27 appeared early in pathogenesis and, at the electron microscopic resolution, had a fibrillary substructure. This shows that a nonexpanded stretch can cause similar histological and behavioral symptoms as the expanded stretch, however, with a significant delay. © 2004 Wiley‐Liss, Inc.