Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular inhibition of carboxylesterases by benzil: modulation of CPT-11 cytotoxicity

Carboxylesterases are ubiquitous proteins responsible for the detoxification of xenobiotics. However, these enzymes also activate prodrugs, such as the anticancer agents capecitabine and CPT-11. As a consequence, overexpression of carboxylesterases within tumor cells sensitizes these cells to CPT-11. We have recently identified two classes of carboxylesterase inhibitors based on either a benzil (diphenylethane-1,2-dione) or a benzene sulfonamide scaffold and showed that these compounds inhibit carboxylesterases with Kis in the low nanomolar range. Because both classes of inhibitors show reversible enzyme inhibition, conventional in vitro biochemical assays would not accurately reflect the in situ levels of carboxylesterase activity or inhibition. Therefore, we have developed a novel assay for the determination of intracellular carboxylesterase activity using 4-methylumbelliferone as a substrate. These studies show that benzil and a dimethylbenzil analogue efficiently enter cells and inhibit human intestinal carboxylesterase and rabbit liver carboxylesterase intracellularly. This inhibition results in reduced cytotoxicity to CPT-11 due to the lack of carboxylesterase-mediated conversion of the prodrug to SN-38. These results suggest that intracellular modulation of carboxylesterase activity with benzil or its analogues may be applied to minimize the toxicity of normal cells to CPT-11. [Mol Cancer Ther 2006;5(9):2281–8]
Spatial Changes in the Bacterial Community Structure along a Vertical Oxygen Gradient in Flooded Paddy Soil Cores

ABSTRACT Molecular ecology techniques were applied to assess changes in the bacterial community structure along a vertical oxygen gradient in flooded paddy soil cores. Microsensor measurements showed that oxygen was depleted from 140 μM at the floodwater/soil interface to nondetectable amounts at a depth of approximately 2.0 mm and below. Bacterial 16S rRNA gene (rDNA)-based community fingerprint patterns were obtained from 200-μm-thick soil slices of both the oxic and anoxic zones by using the T-RFLP (terminal restriction fragment length polymorphism) technique. The fingerprints revealed a tremendous shift in the community patterns in correlation to the oxygen depletion measured with depth. 16S rDNA clone sequences recovered from the oxic or anoxic zone directly corresponded to those terminal restriction fragments which were highly characteristic of the respective zone. Comparative sequence analysis of these clones identified members of the α and β subclasses of Proteobacteria as the abundant populations in the oxic zone. In contrast, members of clostridial cluster I were determined to be the predominant bacterial group in the oxygen-depleted soil. The extraction of total RNA followed by reverse transcription-PCR of the bacterial 16S rRNA and T-RFLP analysis resulted for both oxic and anoxic zones of flooded soil cores in community fingerprint patterns similar to those obtained by the rDNA-based analysis. This finding suggests that the microbial groups detected on the rDNA level are the metabolically active populations within the oxic and anoxic soil slices examined.
Age preferences in mates reflect sex differences in human reproductive strategies

Abstract The finding that women are attracted to men older than themselves whereas men are attracted to relatively younger women has been explained by social psychologists in terms of economic exchange rooted in traditional sex-role norms. An alternative evolutionary model suggests that males and females follow different reproductive strategies, and predicts a more complex relationship between gender and age preferences. In particular, males' preferences for relatively younger females should be minimal during early mating years, but should become more pronounced as the male gets older. Young females are expected to prefer somewhat older males during their early years and to change less as they age. We briefly review relevant theory and present results of six studies testing this prediction. Study 1 finds support for this gender-differentiated prediction in age preferences expressed in personal advertisements. Study 2 supports the prediction with marriage statistics from two U.S. cities. Study 3 examines the cross-generational robustness of the phenomenon, and finds the same pattern in marriage statistics from 1923. Study 4 replicates Study 1 using matrimonial advertisements from two European countries, and from India. Study 5 finds a consistent pattern in marriages recorded from 1913 through 1939 on a small island in the Philippines. Study 6 reveals the same pattern in singles advertisements placed by financially successful American women and men. We consider the limitations of previous normative and evolutionary explanations of age preferences and discuss the advantages of expanding previous models to include the life history perspective.
Time Delay Sliding Mode Control of nonholonomic wheeled mobile robot: Experimental validation

In this endeavor, a hybrid control strategy has been proposed for composite path tracking control of a nonholonomic wheeled mobile robotic (WMR) system under parametric and nonparametric uncertainties. A WMR, often in practical circumstances, undergoes through various parametric changes. Moreover, modeling of WMR in presence of friction, slip or skid, backlash etc. is very difficult. These factors, which make the system model more cumbersome, are normally ignored but their effects are compensated through appropriate control methods. Conventional Sliding Mode Control (SMC) is such a method but it is susceptible to chattering due to high switching gains and reasonable tracking accuracy is sacrificed to avoid chattering. On the other hand, Time Delay Control (TDC) technique is highly efficient to assure robustness against unknown dynamics but it is unable to eliminate approximation errors that arise due to introduced delay. Considering the aforesaid difficulties of SM and TD controllers a hybrid control methodology christened as Time Delay Sliding Mode Control (SMC-TD) is adopted in this work for accurate path tracking of nonholonomic WMR. The SMC-TD is absolutely a judicious blending of SMC and TDC strategies aiming at elimination of the individual shortcomings while retaining the positive advantages. Detail features and advantages of the proposed controller are presented in greater length along with the experimental results, which are very promising.
Radar detection and preclassification based on multiple hypothesis

This work presents a single-scan-processing approach to the problem of detecting and preclassifying a radar target that may belong to different target classes. The proposed method is based on a hybrid of the maximum a posteriori (MAP) and Neyman-Pearson (NP) criteria and guarantees the desired constant false alarm rate (CFAR) behavior. The targets are modeled as subspace random signals having zero mean and given covariance matrix. Different target classes are discriminated based on their different signal subspaces, which are specified by their corresponding projection matrices. Performance is investigated by means of numerical analysis and Monte Carlo simulation in terms of probability of false alarm, detection and classification; the extra signal-to-noise power ratio (SNR) necessary to classify once target detection has occurred is also derived.
Therapeutic collaboration and resistance: Describing the nature and quality of the therapeutic relationship within ambivalence events using the Therapeutic Collaboration Coding System

Abstract Objectives: We understand ambivalence as a cyclical movement between two opposing parts of the self. The emergence of a novel part produces an innovative moment, challenging the current maladaptive self-narrative. However, the novel part is subsequently attenuated by a return to the maladaptive self-narrative. This study focused on the analysis of the therapeutic collaboration in episodes in which a relatively poor-outcome client in narrative therapy expressed ambivalence. Method: For our analysis we used the Therapeutic Collaboration Coding System, developed to assess whether and how the therapeutic dyad is working within the therapeutic zone of proximal development (TZPD). Results: Results showed that when the therapist challenged the client after the emergence of ambivalence, the client tended to invalidate (reject or ignore) the therapist's intervention. Conclusions: This suggests that in such ambivalence episodes the therapist did not match the client's developmental level, and by working outside the TZPD unintentionally contributed to the maintaining the client's ambivalence.
BifA, a Cyclic-Di-GMP Phosphodiesterase, Inversely Regulates Biofilm Formation and Swarming Motility by Pseudomonas aeruginosa PA14

ABSTRACT The intracellular signaling molecule, cyclic-di-GMP (c-di-GMP), has been shown to influence bacterial behaviors, including motility and biofilm formation. We report the identification and characterization of PA4367, a gene involved in regulating surface-associated behaviors in Pseudomonas aeruginosa. The PA4367 gene encodes a protein with an EAL domain, associated with c-di-GMP phosphodiesterase activity, as well as a GGDEF domain, which is associated with a c-di-GMP-synthesizing diguanylate cyclase activity. Deletion of the PA4367 gene results in a severe defect in swarming motility and a hyperbiofilm phenotype; thus, we designate this gene bifA, for biofilm formation. We show that BifA localizes to the inner membrane and, in biochemical studies, that purified BifA protein exhibits phosphodiesterase activity in vitro but no detectable diguanylate cyclase activity. Furthermore, mutational analyses of the conserved EAL and GGDEF residues of BifA suggest that both domains are important for the observed phosphodiesterase activity. Consistent with these data, the ΔbifA mutant exhibits increased cellular pools of c-di-GMP relative to the wild type and increased synthesis of a polysaccharide produced by the pel locus. This increased polysaccharide production is required for the enhanced biofilm formed by the ΔbifA mutant but does not contribute to the observed swarming defect. The ΔbifA mutation also results in decreased flagellar reversals. Based on epistasis studies with the previously described sadB gene, we propose that BifA functions upstream of SadB in the control of biofilm formation and swarming.
Dust formation and survival in supernova ejecta

The presence of dust at high redshift requires efficient condensation of grains in SN ejecta, in accordance with current theoretical models. Yet, observations of the few well studied SNe and SN remnants imply condensation efficiencies which are about two orders of magnitude smaller. Motivated by this tension, we have (i) revisited the model of Todini & Ferrara (2001) for dust formation in the ejecta of core collapse SNe and (ii) followed, for the first time, the evolution of newly condensed grains from the time of formation to their survival - through the passage of the reverse shock - in the SN remnant. We find that 0.1 - 0.6 M⊙ of dust form in the ejecta of 12 - 40 M⊙ stellar progenitors. Depending on the density of the surrounding ISM, between 2-20% of the initial dust mass survives the passage of the reverse shock, on time-scales of about 4 8×10 4 yr from the stellar explosion. Sputtering by the hot gas induces a shift of the dust size distribution towards smaller grains. The resulting dust extinction curve shows a good agreement with that derived by observations of a reddened QSO at z = 6.2. Stochastic heating of small grains leads to a wide distribution of dust temperatures. This supports the idea that large amounts (� 0.1M⊙) of cold dust (T � 40K) can be present in SN remnants, without being in conflict with the observed IR emission.
Functional specialization of domains tandemly duplicated within 16S rRNA methyltransferase RsmC

RNA methyltransferases (MTases) are important players in the biogenesis and regulation of the ribosome, the cellular machine for protein synthesis. RsmC is a MTase that catalyzes the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to G1207 of 16S rRNA. Mutations of G1207 have dominant lethal phenotypes in Escherichia coli, underscoring the significance of this modified nucleotide for ribosome function. Here we report the crystal structure of E. coli RsmC refined to 2.1 Å resolution, which reveals two homologous domains tandemly duplicated within a single polypeptide. We characterized the function of the individual domains and identified key residues involved in binding of rRNA and SAM, and in catalysis. We also discovered that one of the domains is important for the folding of the other. Domain duplication and subfunctionalization by complementary degeneration of redundant functions (in particular substrate binding versus catalysis) has been reported for many enzymes, including those involved in RNA metabolism. Thus, RsmC can be regarded as a model system for functional streamlining of domains accompanied by the development of dependencies concerning folding and stability.
Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice

When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A4 levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c. v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A4 levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A4 induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A4 affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A4 in producing an anxiolytic-like state.
Validity of the Addiction Prone Personality Scale

vi CHAPTER 1: INTRODUCTION . 1 CHAPTER 2: SUBSTANCE USE DISORDERS AND PERSONALITY RESEARCH: A REVIEW OF THE LITERATURE. 13 CHAPTER 3: METHODOLOGY . 64 CHAPTER 4: RESULTS . 76 CHAPTER 5: DISCUSSION . 88 APPENDIX A: ADDICTION-PRONE PERSONALITY (APP) SCALE . 95 APPENDIX B: APP NORMS . 96 APPENDIX C: SASSI-3 . 98 APPENDIX D: GLOSSARY OF TERMS . 102 APPENDIX E: INFORMED CONSENT. 105 APPENDIX F: HUMAN SUBJECTS COMMITTEE APPROVAL MEMORADUM . 106 REFERENCES . 108 BIOGRAPHICAL SKETCH.137
Methods and Applications of Non-Linear Analysis in Neurology and Psycho-physiology

In the light of the results obtained during the last two decades in analysis of signals by time series, it has become evident that the tools of non linear dynamics have their elective role of application in biological, and, in particular, in neuro-physiological and psycho-physiological studies. The basic concept in non linear analysis of experimental time series is that one of recurrence whose conceptual counterpart is represented from variedness and variability that are the foundations of complexity in dynamic processes. Thus, the recurrence plots and the Recurrence Quantification Analysis (RQA) are discussed. It is shown that RQA represents the most general and correct methodology in investigation of experimental time series. By it we arrive to inspect the inner structure of the time series connected to the signals under investigation. Linked to RQA we prospect also the method CZF, recently introduced by us. It is able to account for a true estimation of variability of signals in time as well as in frequency domain. And, consequently, it may be used in conjunction with classical Fourier analysis, accounting however that it is inappropriate in analysis of non linear and non stationary experimental time series. The use of CZF method in fractal analysis is also considered in addition to standard index as Hurst exponent. A large field of possible applications in neurological as well as in psycho-physiological studies is given. Also, there are given examples of other and (possibly linked) applications as example the analysis of beat-to-beat fluctuations of human heartbeat intervals that is sovereign in psycho-physiological studies. We give applications on some different planes to evidence the particular sensitivity of such methods. We reach the objective to show that the previously exposed methods are also able to predict in advance the advent of ventricular tachycardia and/or of ventricular fibrillation. The RQA analysis gives good results. The CZF method gives the most excellent results showing that it is able to give very significant indexes of prediction. We also apply such methods in investigation of state anxiety, and proposing in detail a quantum like model of such phenomenological status of the mind.
On the impact of L2 speech rhythm on syntactic ambiguity resolution

In an event-related potential (ERP) study we investigated the role of age of acquisition (AoA) on the use of second language rhythmic properties during syntactic ambiguity resolution. Syntactically ambiguous sentences embedded in rhythmically regular and irregular contexts were presented to Turkish early and late second language (L2) learners of German and to German monolingual controls. Regarding rhythmic properties, Turkish is syllable-timed and prefers the iamb as its metric foot, while German is stress-timed, relying on the trochee. To utilize rhythm during the processing of syntactic ambiguity in L2, Turkish early and late L2 learners of German must master different rhythmic properties than in their first language. ERPs reveal a reduction in the P600 response to object-first sentences presented in rhythmically regular, but not in rhythmically irregular contexts for early learners and monolinguals only. No such effect was found for late L2 learners. Results indicate an interactive use of rhythmic information during the processing of syntactic ambiguity by monolinguals and early learners. Further, data from late L2 learners suggest that the acquisition of rhythmic properties may have to occur in a sensitive learning period.
Naturalistic Fallacy Errors in Lay Interpretations of Psychological Science: Data and Reflections on the Rind, Tromovitch, and Bauserman (1998) Controversy

The naturalistic fallacy (NF) refers to "is-ought" confusions in which empirical descriptions of nature are seen as dictating moral conclusions. Are brief warnings sufficient to prevent such unwarranted inferences among lay consumers of psychological research? Undergraduates read 2 fictitious news reports, 1 of which summarized a meta-analysis on the effects of childhood sexual abuse (Rind, Tromovitch, & Bauserman, 1998). Students endorsed as "true according to the research" nearly half of the set of NF test statements that asserted moral claims. Including a caution against NF errors had no reliable effect on responses to the sex abuse report; a caution temporarily reduced, but did not eliminate, such errors for an alternative research topic. Additional measures indicated that students-especially those under high cognitive load-perceived the moral views of the researchers as mirroring those of writers citing their work. Implications for recent debates regarding psychological research and public perceptions are discussed.
Combined intraarterial/intravenous thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE The intravenous use of recombinant tissue-type plasminogen activator (rTPA) in acute ischemic stroke has been investigated in three large trials. Limited series have reflected outcome after local intraarterial thrombolysis (LIT) in the cerebral territory. The purpose of this study was to evaluate the safety and efficacy of combined intraarterial/intravenous thrombolysis using rTPA (actilyse) for acute ischemic stroke. METHODS Forty-five patients with acute onset of severe hemispheric stroke and without signs of major cerebral infarction on early CT scans were randomized by order of admission. Twelve patients were treated with 50 mg actilyse (maximal dose, 0.7 mg/kg); three had occlusion of the internal carotid artery and nine had occlusion of the middle cerebral artery. Thrombolysis was started by LIT and continued intravenously within 6 hours of stroke onset. Outcome, assessed after 1 and 12 months according to the modified Rankin scale (MRS), was considered good (MRS score, 0-3) for patients who were functionally independent and poor (MRS score, 4-5) for those who were dependent or had died. RESULTS In the thrombolysis group, outcome was good in eight patients at 1 month and in 10 patients at 12 months; in the control group, outcome was good in seven (21%) and 11 (33%) patients, respectively. Of the eight patients with a good outcome after thrombolysis, four had complete and one had partial recanalization. In the control group, the rate of intracerebral hemorrhage was 6%. Mortality at 1 month in the thrombolysis and control groups was 17% and 48%, respectively. CONCLUSIONS Combined intraarterial/intravenous thrombolysis with low-dose rTPA may be a safe and effective treatment for acute ischemic stroke within 6 hours in carefully selected patients.
Validation of a French measure of body comparison: The Physical Appearance Comparison Scale

Validation francaise d’une mesure de comparaison du corps: l’echelle de comparaison de l’apparence physiqueCette etude a examine la validite d’une version francaise de l’echelle de comparaison de l’apparence physique (PACS ; Thompson, Heinberg, & Tantleff, 1991). Les participants etaient des etudiants (N = 297, 81,1 % de femmes) provenant de deux universites francaises, âges de 18 a 30 ans (M = 20,77, SD = 1,99). La structure factorielle obtenue pour la version francaise du PACS etait semblable a l’echelle originale (Davison & McCabe, 2006), et la coherence interne et la fidelite test-retest etaient bonnes. Les scores des participants sur la version francaise de la PACS sont significativement correles avec le controle du poids, l’auto-evaluation de l’apparence, la satisfaction corporelle, l’anxiete sociale liee a l’apparence, l’estime de soi et la depression. Cette mesure peut aider a mieux comprendre les processus lies a l’insatisfaction corporelle et l’impact de cette insatisfaction sur la detresse psychologique.