Miracle-dz/UniFAR-FTUs huggingface dataset:
N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity

The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression.
Are we testing for true reliability?

The relationship between software testing and reliability is discussed. Two kinds of reliability models, reliability-growth models, which are applied during debugging, and reliability models, which are applied after debugging, are described. Several reasons for the failure of conventional reliability theory in software engineering are presented. It is argued that until random testing of a million points becomes practical, testing for quality is only a poor competitor for other heuristic defect-detection methods. <<ETX>>
Metabolism-Independent Sugar Sensing in Central Orexin Neurons

OBJECTIVE— Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells. RESEARCH DESIGN AND METHODS— We carried out patch-clamp recordings of the electrical activity of individual orexin neurons unambiguously identified by transgenic expression of green fluorescent protein in mouse brain slices. RESULTS— We show that 1) 2-deoxyglucose, a nonmetabolizable glucose analog, mimics the effects of glucose; 2) increasing intracellular energy fuel production with lactate does not reproduce glucose responses; 3) orexin cell glucose sensing is unaffected by glucokinase inhibitors alloxan, d-glucosamine, and N-acetyl-d-glucosamine; and 4) orexin glucosensors detect mannose, d-glucose, and 2-deoxyglucose but not galactose, l-glucose, α-methyl-d-glucoside, or fructose. CONCLUSIONS— Our new data suggest that behaviorally critical neurocircuits of the lateral hypothalamus contain glucose detectors that exhibit novel sugar selectivity and can operate independently of glucose metabolism.
“Ludic Philosophy”: Subjectivity, choice and virtual death in digital media

Time, the irrevocability of choice and commitment as well as the finality of death are central premises in modern moral and political thinking. This irreversibility is understood to reflect something about the organism, and something about the world. As culture comes to be mediated more and more by digital architectures in which time can be skipped, reversed, and begun again, it becomes important to revisit these premises. This paper seeks to bring together thinkers across nations and across disciplines to organize the question of time in the digital age. In particular the relationship between human beings and the virtual/digital world of knowledge databases and online video games.
Effects of doxepin on spatial memory, TNF-α and Bcl-2 family genes expression in rat hippocampus

Introduction: Although the initial hypothesis for the action of doxepin was based on the inhibition of the reuptake of neurotransmitters, it has been suggested that it may also involve other mechanisms. Therefore, this study aims to investigate the effect of doxepin on spatial memory, tumor necrosis factor alpha (TNF-α) level, expression of pro-apoptotic (Bad and Bax) and anti-apoptotic (Bcl-2) genes in the rat hippocampus. Materials and Methods: Male rats were divided randomly into three groups; the control, the doxepin 1 and 5 mg/kg, respectively). Rats received i.p injection of doxepin for 21 days. Spatial memory was evaluated by Morris water maze test. Then the hippocampi were dissected for measurement of the expression of Bcl2, Bad and Bax genes and the TNF-α level. Results: Our results showed no significant effects of doxepin on spatial memory. Doxepin significantly decreased expression of Bad gene, but had no significant/considerable effects on Bcl2 and Bax gene expression. Also, the ratio of TNF-α to total protein (%) did not show significant differences in the rat hippocampus. Conclusion: These results did not show any significant impact of doxepin on the factors affecting the neuronal functions in intact animals. However, Since a significant reduction in the hippocampal Bad mRNA levels was observed It is our assumption that doxepin has neuroprotective effects.
Do I feel dissonance over you? Sex differences in the experience of dissonance for romantic partners

The present research investigated sex differences in the experience of cognitive dissonance after decisions made for oneself or for one’s romantic partner. Guided by theory and research suggesting that women and men possess divergent selfconstruals, I predicted that women would experience more dissonance when making a difficult decision for their partner relative to men. Both men and women were predicted to experience dissonance after decisions made for themselves, although possibly to a lesser degree for women. In two studies, a modified free-choice dissonance paradigm was utilized to test sex differences in the experience of cognitive dissonance, as determined by the extent to which participants justified their decisions. In this paradigm, participants were asked to choose one of two closely rated items either for oneself or for one’s partner. In Study 1, men justified their decision (i.e., enhanced their attitude toward the chosen item and/or derogated the rejected item) when it was made for themselves but not when made for their partner. Females justified decisions made for their romantic partner but not themselves. In Study 2 a self-affirmation manipulation was added to the paradigm such that participants received no self-affirmation (No SA), an independent-focused selfaffirmation (independent SA), or a relationship-focused self-affirmation (relationship SA). As in Study 1, men in the No SA condition justified their decision for themselves but not their partner whereas women justified their decision for their partner but not themselves. Neither men nor women justified decisions in the independent SA condition, as predicted. Males justified their decision for themselves but not their partner in the relationship SA condition, as predicted. Females justified their decisions for their partner in the relationship SA condition, supporting an
Intrapreneurship as a Unique Competitive Advantage

Intrapreneurship, a term used to describe entrepreneurship within existing organizations, has been acknowledged in international literature and practice as a vital element of economic and organizational growth, success and competitiveness and can be considered as a unique competitive advantage. The purpose of the paper is, first, to provide a comprehensive analysis of the concept of intrapreneurship, and, second, to highlight the need for a different approach in the research on the field of intrapreneurship. Concluding, the paper suggests directions for future research. Keywords—Intrapreneurship, entrepreneurship, unique competitive advantage, competitiveness
Electrophysiological interactions of isomers of cyclazocine with the phencyclidine antagonist metaphit in rat cerebellar Purkinje neurons

Metaphit, 1-(1-(3-isothiocyanatophenyl) cyclohexyl) piperidine, an analog of phencyclidine (PCP) has been shown previously to selectively block PCP receptors and to irreversibly antagonize the depressant effect of PCP in cerebellum. In this study, we examined the electrophysiological interactions of metaphit and naloxone with stereoisomers of cyclazocine, an agent known to have analgesic and psychotomimetic activity in behavioral studies, effects that have been ascribed to opiate and PCP receptor activity. A dose-dependent and reversible slowing of Purkinje neuron discharge was seen with local application of (+)- or (-)-cyclazocine. We found that the blockade of (- )-cyclazocine effects required both high doses of naloxone and the presence of metaphit, whereas the responses to (+)-cyclazocine were blocked by metaphit alone on most cerebellar Purkinje neurons. These findings suggest that the depressant reaction of (+)-cyclazocine in cerebellar Purkinje neurons is primarily mediated through PCP receptors. (-)-Cyclazocine responses, on the other hand, appear to be due to activity at both PCP and kappa opioid receptors.
Risk factors and management of conversions to an open approach in laparoscopic liver resection: analysis of 265 consecutive cases.

BACKGROUND As a consequence of continuous technical developments in liver surgery, laparoscopic liver resection (LLR) is increasingly performed worldwide. METHODS Between January 2004 and December 2011, 265 LLR were performed in 242 patients for various diseases. The experience of LLR is reported focusing on risk factors of conversion and their management. RESULTS The overall conversion rate was 17/265 (6.4%), equally distributed over the period of the study. Statistically significant factors for conversion were found to be LLR of the postero-superior (P-S) segments (SI, SIVa; SVII; SVIII) (12.7% converted versus 2.5% non-converted groups, P = 0.01) and a major compared with a minor hepatectomy (15.2% vs. 4.6%, P = 0.02 respectively). A R0 resection was achieved in 93.2% of cases. According to Dindo's classification, complications were recorded as grade I (n = 20); grade II (6); grade III (11) and grade IV(1) events (total morbidity rate of 14%). Univariate analysis identified a major hepatectomy and resection involving P-S segments as prognostic factors for conversion whereas multivariate analysis identified the latter as an independent risk factor [P = 0.003, odds ratio (OR) = 5.9, 95% confidence interval (CI) = 1.8-18.8]. CONCLUSIONS LLR can be safely performed with low overall morbidity. According to this experience and irrespective of the learning curve, resections of P-S segments were identified as an independent risk factor for conversion in LLR.
Dopaminergic enhancement of cognition in old age

As humans age, the brain undergoes many changes. This includes loss of the neurotransmitter dopamine, which forms a bridging link between age and the ensuing changes in cognition. However many questions about the precise nature of this relationship with regards to brain structure and function remain unanswered. These questions are important given our expanding aging population, and the answers may help the discovery of new therapeutic interventions for age-related impairments as well as identify mechanisms to promote successful aging. Old age also provides a model for understanding the role of dopamine in many fundamental human behaviours. The aim of my research was to use a multimodal approach to explore the contribution of dopamine to learning and memory in healthy older age. In this thesis I present four studies in which I used a combination of behavioural testing, pharmacological manipulation, structural and functional magnetic resonance imaging in older adults. I show that dopamine boosts delayed episodic memory in a non-linear dose-dependent manner. Using functional MRI, I show this effect is mediated through consolidation rather than encoding by the hippocampus. In two further imaging studies conducted to explore the role of dopamine in reward-based learning, I show that the flexibility of learning depends on the structural integrity of the substantia nigra/ventral tegmental area (the origin of dopamine projections) and that pharmacological enhancement of dopamine levels can remediate abnormal reward processing in the ventral striatum. Individual differences in neural activity associated with reward prediction also relate to anatomical nigro-striatal connectivity, identified using diffusion tensor imaging. Finally, I show that in old age, valence influences decision-making in relation to ones own beliefs about the future, mediated by volume of the anterior cingulate cortex. I conclude this thesis with a brief discussion of the implications of these findings, study limitations and potential future studies.
Cyclic alkyl amino carbene (CAAC) ruthenium complexes as remarkably active catalysts for ethenolysis.

An expanded family of ruthenium-based metathesis catalysts bearing cyclic alkyl amino carbene (CAAC) ligands was prepared. These catalysts exhibited exceptional activity in the ethenolysis of the seed-oil derivative methyl oleate. In many cases, catalyst turnover numbers (TONs) of more than 100,000 were achieved, at a catalyst loading of only 3 ppm. Remarkably, the most active catalyst system was able to achieve a TON of 340,000, at a catalyst loading of only 1 ppm. This is the first time a series of metathesis catalysts has exhibited such high performance in cross-metathesis reactions employing ethylene gas, with activities sufficient to render ethenolysis applicable to the industrial-scale production of linear α-olefins (LAOs) and other terminal-olefin products.
A peculiar internalization of claudins, tight junction-specific adhesion molecules, during the intercellular movement of epithelial cells

Tight junctions (TJs) seal the intercellular space of epithelial cells, while individual epithelial cells move against adjacent cells in cellular sheets. To observe TJs in live epithelial cellular sheets, green fluorescent protein (GFP) was fused to the N-terminus of claudin-3 (a major cell adhesion molecule of TJs), which was stably expressed at a level that was approximately 50% of that of endogenous claudin-3 in mouse Eph4 epithelial cells. Under confluent culture conditions, individual cells moved within cellular sheets, which was associated with the remodeling of TJs. However, during this remodeling, GFP-positive TJs did not lose their structural continuity. When TJs between two adjacent cells decreased in length during this remodeling, GFP-claudin-3 was frequently pinched off as a granular structure from GFP-positive TJs together with endogenous claudins. Co-culture experiments, as well as electron microscopy, revealed that the two apposed membranes of TJs were not detached, but co-endocytosed into one of the adjacent cells. Interestingly, other TJ components such as occludin, JAM and ZO-1 appeared to be dissociated from claudins before this endocytosis. The endocytosis of claudins was facilitated when the intercellular motility was upregulated by wounding the cellular sheets. These findings suggest that this peculiar internalization of claudins plays a crucial role in the remodeling of TJs, and that the fine regulation of this endocytosis is important for TJs to seal the intercellular space of epithelial cells that are moving against adjacent cells within cellular sheets.
Thymic Tumors

Thymic tumors include thymic carcinoma, which exhibit aggressive behavior, and thymomas, which manifest a more indolent course. Complete resection is the mainstay of treatment, and there appears to be little benefit to partial resection. Postoperative radiotherapy may be useful in incompletely resected patients. Preoperative chemotherapy appears to increase the rate of complete resection and survival of patients with a stage III or IVa thymoma and should strongly be considered in such cases.
Neural correlates of the interaction between transient and sustained processes: A mixed blocked/event‐related fMRI study

Complete understanding of the neural correlates of cognitive processes requires investigation of both event‐ and state‐related correlates of cognitive performance as well as their interaction. Neuroimaging studies using blocked designs confound these two types of processes and studies using event‐related designs focus exclusively on the detection of transient effects. Recent fMRI studies used mixed blocked/event‐related designs and found that transient and sustained activity can be dissociated, but it is not yet known how event‐related and state‐related processing interact. Here we used a phonological categorization paradigm in a mixed blocked/event‐related design to investigate where in the brain transient activity interacts with sustained activity. Task difficulty was parametrically manipulated based on individually determined categorization thresholds. We found an interaction effect of transient and sustained activity in the left precuneus. In this cortical structure transient activity increased with increasing task difficulty, while sustained neural activity decreased with increasing task difficulty. Our data suggest that sustained activity is enhanced during processing of an easy task, presumably because of ongoing internally cued endogenous processing, still allowing effortless processing of transient stimuli. During performance of a difficult task, sustained activity in the precuneus is reduced to provide resources for processing incoming stimuli. Processing of stimuli that are expected to be difficult elicits increased transient responses independent of the actual physical properties of the stimuli. In showing an interaction between transient and sustained activity in the precuneus, the present results accommodate seemingly diverging results from previous studies using event‐related or blocked designs and expand the knowledge emerging from previous studies using mixed blocked/event‐related designs. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
MUC4 Is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma

Purpose: Many of the patients with extrahepatic bile duct carcinoma (EHBDC) show a poor outcome. We have reported that MUC4 is a novel prognostic factor of pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the prognostic significance of MUC4 expression in EHBDC. Experimental Design: We examined the expression profile of MUC4 in EHBDC tissues from 70 patients using immunohistochemistry. MUC4 is a membrane mucin like MUC1. In addition, MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27. We compared the MUC4 expression with MUC1, ErbB2, or p27 expression in EHBDC. Results: MUC4 was expressed in 36 of the 70 patients with EHBDC. There was no significant correlation between the MUC4 expression and MUC1, ErbB2, or p27 expression. The survival of 19 patients with high MUC4 expression (≥20% of carcinoma cells stained) was significantly worse than that of the 51 patients with low MUC4 expression (under 20% of carcinoma cells stained; P = 0.0072). The univariate analysis showed that high MUC4 expression (P = 0.0072), high MUC1 expression (P = 0.0092), histologic grading (P = 0.0029), surgical margin involvement (P = 0.0137), and nodal metastasis (P = 0.0036) were statistically significant risk factors. The backward stepwise multivariate analysis showed that high MUC4 expression (P = 0.0195) and surgical margin involvement (P = 0.0358) were statistically significant independent risk factors. Conclusions: MUC4 expression in EHBDC is a new independent factor for poor prognosis and predicts the outcome of patients with EHBDC.
Speed Control Method of Electric Vehicle for Improving Passenger Ride Quality

This paper proposes the new speed control method of electric vehicles by generating the longitudinal speed pattern for improving the ride comfort against the longitudinal acceleration/deceleration. Since the longitudinal acceleration/deceleration of EVs causes the discomfort of passengers, reducing such bad effect of acceleration/deceleration acting on passengers is very important for not only the ride comfort of passengers but also vehicle running safety. The proposed method is applying the general optimal control theory and it generates the speed pattern for improving the passenger ride quality based on evaluating the variations of acceleration and the jerk which is time derivative of the acceleration. The effectiveness of the present method is demonstrated through numerical experiments compared with some conventional methods.
ATTRACTION OF BARK BEETLES , Tomicus piniperda , Hylurgops palliatus , AND Trypodendron domesticum AND OTHER INSECTS TO SHORT-CHAIN ALCOHOLS AND MONOTERPENES

-Several Scandinavian forest insects, Hylurgops palliatus, Tomicus piniperda, and Trypodendron domesticum (Coleoptera: Scolytidae), Rhizophagus ferrugineus (Coleoptera: Rhizophagidae) and Pollenia spp. (Diptera: Calliphoridae) were attracted to window traps baited with ethanol and placed on Scots pine trees (Pinus sylvestris) in May-June, 1986. Release of ethanol at increasing relative rates of 0, 0.01, 0.1 and 1.0 (800 mg/day) from the window traps on trees in 1987 caused H. palliatus, T. domesticum, and R. ferrugineus to be increasingly attracted, while T. piniperda was equally attracted at both 0.1 and 1.0 rates. The attraction of T. piniperda to ethanol was weak compared to attraction to a monoterpene mix, (+)-c~-pinene, (+)3-carene, terpinolene. The terpene mix plus ethanol was significantly more attractive to H. palliatus than ethanol alone, but terpenes significantly reduced the attraction of T. domesticum to ethanol. Baiting of pipe traps with a series of short-chain alcohols (methanol to hexanol) each alone showed that ethanol was greatly preferred by H. palliatus, 7". domesticum, and R. ferrugineus over alcohols of one more or one less carbon, while longer-chain alcohols were not attractive. However, Glischrochilus hortensis (Col.: Nitidulidae) was attracted only to propanol. A series of 10-fold increasing release rates of ethanol (0.0001-i.0, where 1.0 = 800 mg/day) with either a " low" or "h igh" release of the terpene mix had various effects on the sexes during their attraction to pipe traps and subsequent entering of holes. Release of ( ) verbenone at 0.25 mg/day had no significant effect on 1-1. palliatus or R. ferrugineus attraction to ethanol, but the response of T. domesticum to ethanol was reduced. Several theories on olfactory mechanisms of host selection by T. piniperda are integrated and placed in ecological perspective. Key Words--Host-plant selection, Coleoptera, Scolytidae, Nitidulidae, Rhi-