Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of budesonide on the methylation and mRNA expression of the insulin‐like growth factor 2 and c‐myc genes in mouse lung tumors

The use of surrogate end‐point biomarkers could help in the development of chemopreventive agents. To define potential surrogate end‐point biomarkers, the ability of budesonide to decrease mRNA expression of the insulin‐like growth factor‐2 (Igf‐II) and c‐myc genes and to cause the remethylation of the genes was investigated in lung tumors. Lung tumors were induced in female strain A mice by administering i.p. 16 mg/kg vinyl carbamate for 2 consecutive wk or by a single dose of 100 mg/kg benzo[a]pyrene (B[a]P). Thirty‐four weeks later, the mice given vinyl carbamate received budesonide (0.6 or 2.4 mg/kg diet) for 7 d and then were killed. Mice were killed 24 wk after administration of B[a]P. The mRNA expression of the Igf‐II and c‐myc genes was increased in lung tumors relative to normal lung tissue. Budesonide decreased mRNA expression of both genes in tumors. The methylation status of 27 CpG sites in the differentially methylated region 2 in the Igf‐II gene was determined with the bisulfite‐treated DNA‐sequencing procedure. The numbers of methylated CpG sites were 17–21 in normal lung (70.4 ± 2.6%); 0–2, and 1–2 in lung tumors induced by vinyl carbamate and B[a]P (4.9 ± 1.2% and 4.6 ± 1.2%, respectively); and 4–5 or 7–16 in tumors after treatment with 0.6 or 2.4 mg/kg budesonide (16.0 ± 1.2% and 46.2 ± 5.1%, respectively). Thus, lung tumors had strikingly less methylated CpG sites than normal lung tissue, while even limited treatment with budesonide resulted in remethylation of the CpG sites in tumors. With HpaII digestion followed by Southern blot analysis, the internal cytosine of CCGG sites in the c‐myc gene was found to be methylated in normal lung tissue, whereas some of the sites were unmethylated in lung tumors. Treatment for 7 d with budesonide resulted in the remethylation of these sites. In conclusion, mouse lung tumors showed decreased methylation of the Igf‐II and c‐myc genes that was associated with increased expression of these genes. Budesonide treatment caused remethylation and decreased expression of both genes. The results support the possibility of using decreased mRNA expression and remethylation of the Igf‐II and c‐myc genes as biomarkers for the efficacy of budesonide. © 2002 Wiley‐Liss, Inc.
Electrophysiological properties of lumbar motoneurons in the alpha-chloralose-anesthetized cat during carbachol-induced motor inhibition.

The present study was undertaken 1) to examine the neuronal mechanisms responsible for the inhibition of spinal cord motoneurons that occurs in alpha-chloralose-anesthetized cats following the microinjection of carbachol into the nucleus pontis oralis (NPO), and 2) to determine whether the inhibitory mechanisms are the same as those that are responsible for the postsynaptic inhibition of motoneurons that is present during naturally occurring active sleep. Accordingly, the basic electrophysiological properties of lumbar motoneurons were examined, with the use of intracellular recording techniques, in cats anesthetized with alpha-chloralose and compared with those present during naturally occurring active sleep. The intrapontine administration of carbachol resulted in a sustained reduction in the amplitude of the spinal cord Ia monosynaptic reflex. Discrete large-amplitude inhibitory postsynaptic potentials (IPSPs), which are only present during the state of active sleep in the chronic cat, were also observed in high-gain recordings from lumbar motoneurons after the injection of carbachol. During carbachol-induced motor inhibition, lumbar motoneurons exhibited a statistically significant decrease in input resistance, membrane time constant and a reduction in the amplitude of the action potential's afterhyperpolarization. In addition, there was a statistically significant increase in rheobase and in the delay between the initial-segment (IS) and somadendritic (SD) portions of the action potential (IS-SD delay). There was a significant increase in the mean motoneuron resting membrane potential (i.e., hyperpolarization). The preceding changes in the electrophysiological properties of motoneurons, as well as the development of discrete IPSPs, indicate that lumbar motoneurons are postsynaptically inhibited after the intrapontine administration of carbachol in cats that are anesthetized with alpha-chloralose. These changes in the electrophysiological properties of lumbar motoneurons were found to be comparable with those that take place during the atonia of active (rapid-eye-movement) sleep in chronic cats. The present results support the conclusion that the neural system that is responsible for motor inhibition during naturally occurring active sleep can also be activated in alpha-chloralose-anesthetized cats following the injection of carbachol into the NPO.
Oxidative DNA damage in rats exposed to extremely low frequency electro magnetic fields

Extremely low frequency (ELF) electromagnetic field (EMF) is thought to prolong the life of free radicals and can act as a promoter or co-promoter of cancer. 8-hydroxy-2′-deoxyguanosine (8OHdG) is one of the predominant forms of radical-induced lesions to DNA and is a potential tool to asses the cancer risk. We examined the effects of extremely low frequency electro magnetic field (ELF-EMF) (50 Hz, 0.97 mT) on 8OHdG levels in DNA and thiobarbituric acid reactive substances (TBARS) in plasma. To examine the possible time-dependent changes resulting from magnetic field, 8OHdG and TBARS were quantitated at 50 and 100 days. Our results showed that the exposure to ELF-EMF induced oxidative DNA damage and lipid peroxidation (LPO). The 8OHdG levels of exposed group (4.39±0.88 and 5.29±1.16 8OHdG/dG.105, respectively) were significantly higher than sham group at 50 and 100 days (3.02±0.63 and 3.46±0.38 8OHdG/dG.105) (p<0.001, p<0.001). The higher TBARS levels were also detected in the exposure group both on 50 and 100 days (p<0.001, p<0.001). In addition, the extent of DNA damage and LPO would depend on the exposure time (p<0.05 and p<0.05). Our data may have important implications for the long-term exposure to ELF-EMF which may cause oxidative DNA damage.
Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus Protease

ABSTRACT Feline immunodeficiency virus (FIV) protease is structurally very similar to human immunodeficiency virus (HIV) protease but exhibits distinct substrate and inhibitor specificities. We performed mutagenesis of subsite residues of FIV protease in order to define interactions that dictate this specificity. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. FIV proteases all failed to cut HIV-1 matrix/capsid, P1/P6, P6/protease, and protease/reverse transcriptase junctions, indicating that none of the substitutions were sufficient to change the specificity completely. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. The data also suggest that FIV protease prefers a hydrophobic P2/P2′ residue like Val over Asn or Glu, which are utilized by HIV-1 protease, and that S2/S2′ might play a critical role in distinguishing FIV and HIV-1 protease by specificity. The findings extend our observations regarding the interactions involved in substrate binding and aid in the development of broad-based inhibitors.
Intention in articulation: Articulatory timing in alternating consonant sequences and its implications for models of speech production

Several studies have reported that during the production of phrases with alternating consonants (e.g., top cop), the constriction gestures for these consonants can come to be produced in the same prevocalic position. Since these coproductions occur in contexts that also elicit segmental substitution errors, the question arises whether they may result from monitoring and repair, or whether they arise from the architecture of the phonological and phonetic planning process. This paper examines the articulatory timing of the coproduced gestures in order to shed light on the underlying process that gives rise to them. Results show that overall at movement onset the gestures are mostly synchronous, but it is the intended consonant that is released last. Overall the data support the view that the activation of two gestures is inherent to the speech production process itself rather than being due to a monitoring process. We argue that the interactions between planning and articulatory dynamics apparent in our data require a more comprehensive approach to speech production than is provided by current models.
Decoupling Interval Timing and Climbing Neural Activity: A Dissociation between CNV and N1P2 Amplitudes

It is often argued that climbing neural activity, as for example reflected by the contingent negative variation (CNV) in the electroencephalogram, is the signature of the subjective experience of time. According to this view, the resolution of the CNV coincides with termination of subjective timing processes. Paradoxically, behavioral data indicate that participants keep track of timing even after the standard interval (SI) has passed. This study addresses whether timing continues after CNV resolution. In Experiment 1, human participants were asked to discriminate time intervals while evoked potentials (EPs) elicited by the sound terminating a comparison interval (CI) were measured. As the amplitude of N1P2 components increases as a function of the temporal distance from the SI, and the latency of the P2 component followed the hazard rate of the CIs, timing processes continue after CNV resolution. Based on a novel experimental paradigm, statistical model comparisons and trial-by-trial analyses, Experiment 2 supports this finding as subjective time is more accurately indexed by the amplitude of early EPs than by CNV amplitude. These results provide the first direct evidence that subjective timing of multisecond intervals does not depend on climbing neural activity as indexed by the CNV and that the subjective experience of time is better reflected by distinct features of post-CI evoked potentials.
Port placement planning in robot-assisted coronary artery bypass

Properly selected port sites for robot-assisted coronary artery bypass graft (CABG) improve the efficiency and quality of these procedures. In clinical practice, surgeons select port locations using external anatomic landmarks to estimate a patient's internal anatomy. This paper proposes an automated approach to port selection based on a preoperative image of the patient, thus avoiding the need to estimate internal anatomy. Using this image as input, port sites are chosen from a grid of surgeon-approved options by defining a performance measure for each possible port triad. This measure seeks to minimize the weighted squared deviation of the instrument and endoscope angles from their optimal orientations at each internal surgical site. This performance measure proves insensitive to perturbations in both its weighting factors and moderate intraoperative displacements of the patient's internal anatomy. A validation study of this port site selection was performed. cardiac algorithm also Six surgeons dissected model vessels using the port triad selected by this algorithm with performance compared to dissection using a surgeon-selected port triad and a port triad template described by Tabaie et al., 1999. With the algorithm-selected ports, dissection speed increased by up to 43% (p = 0.046) with less overall vessel trauma. Thus, this algorithmic approach to port site selection has important clinical implications for robot-assisted CABG which warrant further investigation.
Trisomy 9q3 syndrome: a case report and review of the literature

A girl with partial trisomy 9q is reported. She was characterized by dolichomorphism, abnormalities of the digits, a cardiac defect and craniofacial dysmorphism. A high‐resolution analysis revealed the karyotype to be: 46,XX,‐3,+der(3)t(3;9)(q29;q13) de novo. A phenotype‐karyo‐type correlation study in 22 cases of partial trisomies 9q supported the delineation of a trisomy 9q3 syndrome. The smallest region of overlap was confined to 9q32.
Proton Magnetic Resonance Spectroscopic Imaging in Neonatal Stroke

To study cerebral metabolism in neonates after unilateral cerebral infarcts 4 neonates (3 full-terms, one preterm with a gestational age of 35 weeks) with unilateral cerebral infarcts were examined at 7 to 49 days of postnatal age, using proton magnetic resonance spectroscopic imaging (1H-MRSI). Three neonates had infarcts of the left middle cerebral artery (MCA), one had a right posterior cerebral artery infarct and a more localized anterior lesion. Examinations were repeated in the three fullterm infants aged 2-3 months. Lactate resonances, which are not present in normal brain after term age, were demonstrated in two patients tested at 7 and 10 days of age respectively, and in one of them lactate was still present at two months. In all four neonates a decrease of the N-acetylaspartate/choline (NAA/Cho) ratio was seen within the area of infarction. Repeated MRS of two infants at three months showed an increase in NAA/Cho ratios in all brain areas, but values remained below normal in the infarcts. In the third infant a further decrease in the NAA/Cho ratio was demonstrated in the area of infarction at two months. The NAA/Cho ratios in the surrounding and contralateral brain tissue were normal in all infants. All three infants with a MCA infarct developed a hemiplegia. The aforementioned metabolic alterations in neonates with cerebral infarcts, demonstrated using 1H-MRSI, were found to be confined to the area of infarction and abnormalities persisted beyond the neonatal period.
Pathways to Meaning-Making Through Leisure-Like Pursuits in Global Contexts

Abstract This paper incorporates international and multicultural perspectives on meaning- making through leisure-like pursuits, by acknowledging voices of non-western people including Asians, Middle-Easterners, Indigenous persons, Africans, and South Americans, in addition to some dominant Euro-North American perspectives. Based on a literature review and content analysis and synthesis, major pathways linking leisurelike pursuits to meaning-making are identified, specifically, their roles in facilitating: (a) positive emotions and well-being; (b) positive identities, self-esteem, and spirituality; (c) social and cultural connections and a harmony; (d) human strengths and resilience; and (e) learning and human development across the life-span. More generally, however, in people's quest for a meaningful life, the processes of meaning-making through leisure-like engagements involve both remedying the bad and enhancing the good. Achieving a more balanced understanding of leisure-like engagements and meaning-making as a global phenomenon is implied and advocated.
Approximation Algorithms and New Models for Clustering and Learning

This thesis is divided into two parts. In part one, we study the k-median and the k-means clustering problems. We take a different approach than the traditional worst case analysis models. We show that by looking at certain well motivated stable instances, one can design much better approximation algorithms for these problems. Our algorithms achieve arbitrarily good approximation factors on stable instances, something which is provably hard on worst case instances. We also study a different model for clustering which introduces limited amount of interaction with the user. Such interactive models are very popular in the context of learning algorithms but their effectiveness for clustering is not well understood. We present promising theoretical and experimental results in this direction. The second part of the thesis studies the design of provably good learning algorithms which work under adversarial noise. One of the fundamental problems in this area is to understand the learnability of the class of disjunctions of Boolean variables. We design a learning algorithm which improves on the guarantees of the previously best known result for this problem. In addition, the techniques used seem fairly general and promising to be applicable to a wider class of problems. We also propose a new model for learning with queries. This model restricts the algorithms ability to only ask certain “local” queries. We motivate the need for the model and show that one can design efficient local query algorithms for a wide class of problems.
Domain-driven data synopses for dynamic quantiles

In this paper, we present new algorithms for dynamically computing quantiles of a relation subject to insert as well as delete operations. At the core of our algorithms lies a small-space multiresolution representation of the underlying data distribution based on random subset sums or RSSs. These RSSs are updated with every insert and delete operation. When quantiles are demanded, we use these RSSs to estimate quickly, without having to access the data, all the quantiles, each guaranteed to be accurate to within user-specified precision. While quantiles have found many uses in databases, in this paper, our focus is primarily on network management applications that monitor the distribution of active sessions in the network. Our examples are drawn both from the telephony and the IP network, where the goal is to monitor the distribution of the length of active calls and IP flows, respectively, over time. For such applications, we propose a new type of histogram that uses RSSs for summarizing the dynamic parts of the distributions while other parts with small volume of sessions are approximated using simple counters.
Effects of Student Evaluation Feedback: A Meta-Analysis of Higher Education Research.

On many campuses, student ratings of courses and teachers are routinely given to instructors as feedback about their teaching. This review applies meta-analytic techniques to 30 studies of the effectiveness of student ratings feedback. The studies met the following criteria: (1) they used student ratings as the primary source of feedback; (2) they investigated post secondary instruction; (3) they were conducted in the classroom rather than laboratory settings; (4) they employed a control group for comparison purposes; and (5) they stood apart from larger training programs in which the effects of feedback are inseparable from the effects of training. Results indicated that feedback from student ratings alone produceF, a positive but small effect on subsequent ratings. When ratings were accompanied by consultation and/or other types of feedback, considerably larger poaitive effects were likely. In the few studies of feedback's effects on student achievement and affect, results were less clear. Future research should: (1) investigate additional dependent variables; (2) more carefully document and investigate feedback implementations; and (3) explore additional characteristics of the recip:ents if feedback. The studies analyzed in this review are attatchad, as well as a listing of those studies which did not meet criteria for meta-analysis (JD) *********************************************************************** Reproductions supplied by EDRF are the best that can be made from the original document. *********************************************************************** Effects of Student Evaluation Feedback: A Meta-Analysis of Higher Education Research Robert J. Menges and Kathleen T. Brinko Northwestern University The Center for the Teaching Professions Northwestern University
The Parkinson Disease-associated Leucine-rich Repeat Kinase 2 (LRRK2) Is a Dimer That Undergoes Intramolecular Autophosphorylation*

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and apparently sporadic Parkinson disease. LRRK2 is a multidomain protein kinase with autophosphorylation activity. It has previously been shown that the kinase activity of LRRK2 is required for neuronal toxicity, suggesting that understanding the mechanism of kinase activation and regulation may be important for the development of specific kinase inhibitors for Parkinson disease treatment. Here, we show that LRRK2 predominantly exists as a dimer under native conditions, a state that appears to be stabilized by multiple domain-domain interactions. Furthermore, an intact C terminus, but not N terminus, is required for autophosphorylation activity. We identify two residues in the activation loop that contribute to the regulation of LRRK2 autophosphorylation. Finally, we demonstrate that LRRK2 undergoes intramolecular autophosphorylation. Together, these results provide insight into the mechanism and regulation of LRRK2 kinase activity.
Self-adaptive and self-optimising resource monitoring for dynamic grid environments

As the number of resources on the grid tends to be very dynamic and potentially large, it becomes increasingly important to discover and monitor them efficiently. This paper concentrates on the scalability, reliability and performance of grid discover and monitoring services, using autonomous concepts. Application scenarios are developed where the notification rate of data is dynamically modified, based on the overhead costs at the MDS3 Index Service. Previously collected performance benchmarks are also utilised to implement two self-adaptive algorithms which are the basis of the scenarios. The objective of these feedback algorithms is to sustain an adequate level of service for clients while minimising costs at the MDS. Different types of workload models are also used to assess the efficiency of the algorithms. Experimental results are subsequently shown when varying notification update mechanisms and decision parameters are used, ensuring that the MDS is scalable with accruing concurrent clients. Therefore, a policy is proposed where the notification rate is computed dynamically, thereby creating an autonomous grid monitoring service.
VASCULAR ASSOCIATED DEATH1, a Novel GRAM Domain–Containing Protein, Is a Regulator of Cell Death and Defense Responses in Vascular Tissues

The hypersensitive response (HR) is a programmed cell death that is commonly associated with plant disease resistance. A novel lesion mimic mutant, vad1 (for vascular associated death1), that exhibits light conditional appearance of propagative HR-like lesions along the vascular system was identified. Lesion formation is associated with expression of defense genes, production of high levels of salicylic acid (SA), and increased resistance to virulent and avirulent strains of Pseudomonas syringae pv tomato. Analyses of the progeny from crosses between vad1 plants and either nahG transgenic plants, sid1, nonexpressor of PR1 (npr1), enhanced disease susceptibility1 (eds1), or non-race specific disease resistance1 (ndr1) mutants, revealed the vad1 cell death phenotype to be dependent on SA biosynthesis but NPR1 independent; in addition, both EDS1 and NDR1 are necessary for the proper timing and amplification of cell death as well as for increased resistance to Pseudomonas strains. VAD1 encodes a novel putative membrane-associated protein containing a GRAM domain, a lipid or protein binding signaling domain, and is expressed in response to pathogen infection at the vicinity of the hypersensitive lesions. VAD1 might thus represent a new potential function in cell death control associated with cells in the vicinity of vascular bundles.