Miracle-dz/UniFAR-FTUs huggingface dataset:
WAY‐100635 antagonist‐induced plasticity of 5‐HT1A receptors: regulatory differences between a stable cell line and an in vivo native system

We present evidence that the 5‐hydroxytryptamine1A (5‐HT1A) receptor antagonist, N‐{2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]‐ethyl}‐N‐(2‐pyridinyl)cyclohexanecarboxamide (WAY‐100635), can induce receptor internalization in a human (h)5‐HT1A receptor Chinese hamster ovary (CHO‐K1) cell system. Exposure of h5‐HT1A CHO cells to WAY‐100635 decreased the cell‐surface h5‐HT1A receptor density in a way that was both time (24–72 h) and concentration (1–100 nm) dependent. [3H]WAY‐100635 and [3H]8‐hydroxy‐dipropylaminotetralin ([3H]8‐OH‐DPAT) saturation analyses demonstrated a significant reduction (50–60%) in total h5‐HT1A receptor number in the WAY‐100635‐treated (100 nm; 72 h) compared with control cells. In WAY‐100635‐treated cells, the 8‐OH‐DPAT‐mediated inhibition of forskolin (FSK)‐stimulated cAMP accumulation was right‐shifted and the maximal inhibitory response of 8‐OH‐DPAT was impaired compared with control cells. Similar results were obtained for 8‐OH‐DPAT‐mediated Ca2+ mobilization after WAY‐100635 treatment. h5‐HT1A receptors labeled with [3H]WAY‐100635, as well as [3H]4‐(2′‐Methoxy)‐phenyl‐1‐[2′‐(N‐2′′‐pyridinyl)‐p‐fluorobenzamido]ethyl‐piperazine (MPPF), exhibited a time‐dependent rate of cellular internalization that was blocked by endocytotic suppressors and was pertussis‐toxin insensitive. In contrast, quantitative autoradiographic studies demonstrated that chronic treatment of rats with WAY‐100635 for two weeks produced a region‐specific increase in the 5‐HT1A receptor density. In conclusion, prolonged exposure of an h5‐HT1A cell‐based system to the 5‐HT1A antagonist, WAY‐100635, induced a paradoxical internalization of cell surface receptor resulting in depressed functional activity. This suggests that an antagonist can influence 5‐HT1A receptor recycling in vitro differently to in vivo regulatory conditions.
The Reelin and GAD67 Promoters Are Activated by Epigenetic Drugs That Facilitate the Disruption of Local Repressor Complexes

The epigenetic down-regulation of genes is emerging as a possible underlying mechanism of the GABAergic neuron dysfunction in schizophrenia. For example, evidence has been presented to show that the promoters associated with reelin and GAD67 are down-regulated as a consequence of DNA methyltransferase (DNMT)-mediated hypermethylation. Using neuronal progenitor cells to study this regulation, we have previously demonstrated that DNMT inhibitors coordinately increase reelin and GAD67 mRNAs. Here, we report that another group of epigenetic drugs, histone deacetylase (HDAC) inhibitors, activate these two genes with dose and time dependence comparable with that of DNMT inhibitors. In parallel, both groups of drugs decrease DNMT1, DNMT3A, and DNMT3B protein levels and reduce DNMT enzyme activity. Furthermore, induction of the reelin and GAD67 mRNAs is accompanied by the dissociation of repressor complexes containing all three DNMTs, MeCP2, and HDAC1 from the corresponding promoters and by increased local histone acetylation. Our data imply that drug-induced promoter demethylation is relevant for maximal activation of reelin and GAD67 transcription. The results suggest that HDAC and DNMT inhibitors activate reelin and GAD67 expression through similar mechanisms. Both classes of drugs attenuate, directly or indirectly, the enzymatic and transcriptional repressor activities of DNMTs and HDACs. These data provide a mechanistic rationale for the use of epigenetic drugs, individually or in combination, as a potential novel therapeutic strategy to alleviate deficits associated with schizophrenia.
Selective Preservation of Bone Marrow Mature Recirculating but Not Marginal Zone B Cells in Murine Models of Chronic Inflammation

Inflammation promotes granulopoiesis over B lymphopoiesis in the bone marrow (BM). We studied B cell homeostasis in two murine models of T cell mediated chronic inflammation, namely calreticulin-deficient fetal liver chimeras (FLC), which develop severe blepharitis and alopecia due to T cell hyper responsiveness, and inflammatory bowel disease (IBD) caused by injection of CD4+ naïve T cells into lymphopenic mice. We show herein that despite the severe depletion of B cell progenitors during chronic, peripheral T cell-mediated inflammation, the population of BM mature recirculating B cells is unaffected. These B cells are poised to differentiate to plasma cells in response to blood borne pathogens, in an analogous fashion to non-recirculating marginal zone (MZ) B cells in the spleen. MZ B cells nevertheless differentiate more efficiently to plasma cells upon polyclonal stimulation by Toll-like receptor (TLR) ligands, and are depleted during chronic T cell mediated inflammation in vivo. The preservation of mature B cells in the BM is associated with increased concentration of macrophage migration inhibitory factor (MIF) in serum and BM plasma. MIF produced by perivascular dendritic cells (DC) in the BM provides a crucial survival signal for recirculating B cells, and mice treated with a MIF inhibitor during inflammation showed significantly reduced mature B cells in the BM. These data indicate that MIF secretion by perivascular DC may promote the survival of the recirculating B cell pool to ensure responsiveness to blood borne microbes despite loss of the MZ B cell pool that accompanies depressed lymphopoiesis during inflammation.
Dynamical eigenfunction decomposition of turbulent channel flow

The results of an analysis of low-Reynolds-number turbulent channel flow based on the Karhunen-Loeve(K-L) expansion are presented. The turbulent flow field is generated by a direct numerical simulation of the Navier-Stokes equations at a Reynolds number Re,= 80 (based on the wall shear velocity and channel half-width). The K-L procedure is then applied to determine the eigenvalues and eigenfunctions for this flow. The random coefficients of the K-L expansion are subsequently found by projecting the numerical flow field onto these eigenfunctions. The resulting expansion captures 90% of the turbulent energy with significantly fewer modes than the original trigonometric expansion. The eigenfunctions, which appear either as rolls or shearing motions, posses viscous boundary layers at the walls and are much richer in harmonics than the original basis functions. Chaotic temporal behaviour is observed in all modes and increases for higher-order eigenfunctions. The structure and dynamical behaviour of the eigenmodes are discussed as well as their use in the representation of the turbulent flow.
Optimal allocation of carry-save-adders in arithmetic optimization

Carry-save-adder(CSA) is one of the most widely used schemes for fast arithmetic in industry. This paper provides a solution to the problem of finding an optimal-timing allocation of CSAs. Specifically, we present a polynomial time algorithm which finds an optimal-timing CSA allocation for a given arithmetic expression. In addition, we extend our result for CSA allocation to the problem of optimizing arithmetic expressions across the boundary of design hierarchy by introducing a new concept, called auxiliary ports. Our algorithm can be used to carry out the CSA allocation step optimally and automatically, and this can be done within the context of a standard HDL synthesis environment.
Integration between abutting retinas: role of glial structures and associated molecules at the interface.

PURPOSE Integration between subretinal grafts and the host retina is limited in part by the presence of a barrier at the graft-host interface. This study was conducted to identify factors that may contribute to this barrier, by examining the distribution of glial structures and associated molecules in different setups of overlapping retinal pieces. METHODS Neuroretinal tissue derived from mice that express green fluorescent protein (GFP) was fragmented and transplanted into the subretinal space of adult rd1 mice. In an in vitro system, two retinal pieces, derived from GFP and rd1 mice, respectively, were placed overlapping each other and forming either laminar-laminar pairs or fragment-laminar pairs. The glia-associated markers analyzed included glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), and two molecules known to inhibit neurite outgrowth: CD44 and neurocan. Bridging fibers and migrated cells were visualized with GFP fluorescence and retinal cell markers. RESULTS A thick CRALBP-immunolabeled band was observed in the interface in cultured laminar-laminar pairs, whereas a thinner band was seen in cultured fragment-laminar pairs and in transplants. Accumulation of CD44 and neurocan was also observed in the interface between abutting retinal pieces in all setups. GFP(+) bridging fibers and GFP(+) cells (some of which coexpressed neuronal markers) were observed within the abutting rd1 retina in some areas. However, such integration occurred exclusively where CRALBP, CD44, and neurocan immunolabeling appeared disrupted in the interface, but coincided with high GFAP expression within the rd1 retina. CONCLUSIONS The results demonstrate that, on the one hand, an accumulation of glial-associated inhibitory molecules in the interface correlates with limited integration between overlapping retinal pieces. On the other hand, glial reactivity within the rd1 retina does not appear to be incompatible with integration.
Tangible autonomous interfaces (TAIs): exploring autonomous behaviours in TUIs

The use of autonomous behaviour in Tangible User Interfaces can potentially create a compelling and new kind of interaction between humans and computers. We motivate this argument by reviewing related research, which indicates that people are engaged by apparently autonomous behaviours in tangible objects and apply rules of social behaviour towards these smart objects. Our intention is to leverage this effect in support of human-computer interaction. Rather than aiming to improve user performance, we argue that such interfaces can offer a richer and more enjoyable autonomous interface interaction. Herein we present a framework highlighting key concepts and characteristics which are important while designing and implementing Tangible Autonomous Interfaces.
Soil hydraulic parameters estimated from satellite information through data assimilation

Leaf area index (LAI) and actual evapotranspiration (ETa) from satellite observations were used to estimate simultaneously the soil hydraulic parameters of four soil layers down to 60 cm depth using the combined soil water atmosphere plant and genetic algorithm (SWAP–GA) model. This inverse model assimilates the remotely sensed LAI and/or ETa by searching for the most appropriate sets of soil hydraulic parameters that could minimize the difference between the observed and simulated LAI (LAIsim) or simulated ETa (ETasim). The simulated soil moisture estimates derived from soil hydraulic parameters were validated using values obtained from soil moisture sensors installed in the field. Results showed that the soil hydraulic parameters derived from LAI alone yielded good estimations of soil moisture at 3 cm depth; LAI and ETa in combination at 12 cm depth, and ETa alone at 28 cm depth. There appeared to be no match with measurement at 60 cm depth. Additional information would therefore be needed to better estimate soil hydraulic parameters at greater depths. Despite this inability of satellite data alone to provide reliable estimates of soil moisture at the lowest depth, derivation of soil hydraulic parameters using remote sensing methods remains a promising area for research with significant application potential. This is especially the case in areas of water management for agriculture and in forecasting of floods or drought on the regional scale.
Release of Platelet‐Activating Factor in Acute Experimental Pancreatitis

This study demonstrates the formation of platelet-activating factor (PAF) in rats with acute experimental pancreatitis (AEP). The AEP was induced by infusing sodium taurodeoxycholate and trypsin into the bile-pancreatic duct. The PAF content was increased in blood samples and in pulmonary and pancreatic tissue as compared with control animals. Significant amounts of PAF were also found in peritoneal fluid. The PAF content did increase in blood samples and in pulmonary tissue after administration of endotoxin intravenously. The effects of intraperitoneal PAF administration were also studied and showed an increase of polymorphonuclear cells in blood samples. These findings suggest that acute pancreatitis might generate and release PAF. Whether PAF release is associated with the pathophysiology of complications in acute pancreatitis remains to be elucidated.
Neuronal Spike Sorting Based on 2-Stage RBF Networks

In this paper, 2-stage Radial Basis Function (RBF) network method is used for neural spike sorting. Firstly, raw signals are obtained from neural signal simulator, and added white noise ranged from -10 dB to -40 dB. Secondly, spikes are detected out with matched filter from signals. Lastly, 2-stage RBF networks are constructed and the spikes are sorted using RBF networks. The experiments show that 2-stage RBF network is an effective tool for neural spike sorting.
Detection Of Faking on the Comrey Personality Scales.

The ability of subjects to fake responses on personality tests under various experimental conditions has been established in several studies, including those involving the Comrey Personality Scales (CPS). Evidence is presented in this study regarding the potential of several techniques for detecting faked CPS test records, along with a further demonstration of the extent to which the CPS can be faked. Five groups of test records were used: four were from two sets of university student subjects, with one test record completed under normal conditions and the other under instructions to deliberately "fake good. " The final group of CPS records was from a set of police officer candidates. Several possible faking predictor scores were related to a continuously measured index of faking based on differences between "faked" and "normal" records and also to a dichotomous criterion of faking. Results of a correlational analysis show that the best predictor of faking on the Comrey Personality Scales is a total summary score obtained by adding up all ten CPS scale scores.
Experiential Motivations of Socially Responsible Consumption

This paper uses the experiential marketing concept to explain some of the motivations for socially responsible consumption. It is argued that practising responsible behaviour helps consumers to perceive five different types of experiential value: emotional, cognitive, sensory, relational and behavioural. A web-based survey on a panel of more than 1,000 North American respondents confirmed the presence of an average level of each experiential value type in responsible decisions. We also found evidence for gender and age differences in the perception of those experiential benefits. This study provides guidelines to better promote socially responsible consumption through enriching consumers' experiential motivations. The findings of this study also provide ideas for demographic-based targeting of responsible goods/services.
One Step Ahead MPC for an Automotive Control Application

The problem considered in this paper is to damp out the longitudinal driveline oscillations that appear during gearshift, while traversing backlash or when tip-in and tip-out maneuvers are performed. MPC is increasingly seen as an attractive technology, as such, a one step ahead robust and efficient predictive controller is proposed, based on a flexible control Lyapunov functions. The algorithm has the potential to satisfy the timing requirements for a real-time control application, due to the short horizon, while it can still offer a non-conservative solution to stabilization due to the flexibility of the Lyapunov function.
Neighbourhoods matter too: the association between neighbourhood socioeconomic position, population density and breast, prostate and lung cancer incidence in Denmark between 2004 and 2008

Background Previous studies have shown that cancer incidence is related to a number of individual factors, including socioeconomic status. The aim of this study was to refine the current knowledge about indicators associated with cancer incidence by evaluating the influence of neighbourhood characteristics on breast, prostate and lung cancer incidence in Denmark. Methods All women aged 30–83 years were followed for breast cancer between 2004 and 2008, men between 50 and 83 years were followed for prostate cancer and both sexes between ages 50 and 83 were followed for lung cancer. Registry data obtained from Statistics Denmark included age, sex, availability of breast cancer screening, marital status, education, disposable income and occupational socioeconomic status on the individual level and population density and neighbourhood socioeconomic status (the proportion of unemployed) on the parish level. Frailty modelling with individuals on the first level and parishes on the second level was conducted. Results A significantly lower HR of breast cancer was found in areas with low population density (HR=0.93; CI 0.88 to 0.99), while neighbourhood unemployment had no effect. Inhabitants of lower unemployment areas had a higher risk of prostate cancer (HR=1.14; CI 1.08 to 1.21) compared with those in higher unemployment areas, whereas population density had no effect. Risk of lung cancer was lower in areas with lowest population density (HR=0.80; CI 0.74 to 0.85) and lowest in areas with lowest unemployment (HR=0.88; CI 0.84 to 0.92). Conclusions In addition to individual-level factors, characteristics on the neighbourhood level also have an influence on breast, prostate and lung cancer incidence.
Novel platinum(IV) complexes induce rapid tumor cell death in vitro

The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)‐based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum‐based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)‐based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine‐N,N′‐di‐3‐propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress‐independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical‐mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. © 2005 Wiley‐Liss, Inc.
Cellular and chemical dynamics within the nucleus accumbens during reward -related learning and decision making

JEREMY DAY: Cellular and Chemical Dynamics within the Nucleus Accumbens during Reward-related Learning and Decision Making (Under the direction of Regina M. Carelli) The ability to form and maintain associations between environmental cues, actions, and rewarding stimuli is an elementary yet fundamental aspect of learned behavior. Moreover, in order for organisms to optimize behavioral allocation after learning has occurred, such associations must be able to guide decision making processes as animals weigh the benefits and costs of potential actions. Multiple lines of research have identified that reward-related learning and decision making are mediated by a distributed network of brain nuclei that includes the nucleus accumbens (NAc) and its innervation from dopamine neurons located in the midbrain. However, the precise neural processing that underlies this function is unclear. The first set of experiments detailed in this dissertation took advantage of technological advances to characterize patterns of NAc dopamine release in real time, during behavioral performance. The results of the first experiment demonstrate for the first time that rapid dopamine release in the NAc is dramatically altered during stimulus-reward learning. Before learning, reward delivery produced robust increases in NAc dopamine concentration. After learning, these increases had completely transferred to the predictive cue and were no longer present when rewards were delivered. Further experiments revealed that cue-evoked increases in NAc dopamine concentration did not signal reward prediction alone, but reflected the
Modeling emotion expression and perception behavior in auditive emotion evaluation

In this paper, we consider both speaker dependent and listener dependent aspects in the assessment of emotions in speech. We model the speaker dependencies in emotional speech production by two parameters which describe the individual’s emotional expression behavior. Similarly, we model the listener’s emotion perception behavior by a simple parametric model. These models form a basis for improving current automatic emotion recognition schemes such as, for example, for manmachine interaction applications. For this task, an emotional speech database of the four emotion categories angry, happy, neutral, and sad was evaluated by 18 human listeners. For each of the 680 sentences, the evaluators rated the values of three emotion primitives, valence, activation, and dominance, each on a 5-point scale. The assessment results were used to calculate the distributions (centroids, covariances) of the emotion classes in the space spanned by the three emotion primitives. The individual classes formed separable clusters in the emotion space. Based on these results, we analyzed the variations of the emotion clusters as a function of speaker and listener. Across different speakers, we found that the main difference in the emotional speech was the position of the neutral cluster and the scaling of the emotions in the emotion primitives space. To capture this effect, we introduced the speaker-dependent parameters Emotion Expression Bias and Emotion Expression Amplification within this model representation and showed that the original class centroids could be reconstructed fairly accurately. From the perception viewpoint, we found that the listeners’ ratings of emotional speech could be described as a realization of a normally distributed random variable. Based on this result, we propose the correlation with the mean value of the ratings to be the listener-dependent parameter, which could be in turn incorporated within the model training for automatic recognition.
LLTools: Machine Learning for Human Language Processing

Machine learning methods in Human Language Technology have reached a stage of maturity where widespread use is both possible and desirable. The MIT Lincoln Laboratory LLTools software suite provides a step towards this goal by providing a set of easily accessible frameworks for incorporating speech, text, and entity resolution components into larger applications. For the speech processing component, the pySLGR (Speaker, Language, Gender Recognition) tool provides signal processing, standard feature analysis, speech utterance embedding, and machine learning modeling methods in Python. The text processing component in LL-Tools extracts semantically meaningful insights from unstructured data via entity extraction, topic modeling, and document classiﬁcation. The entity resolution component in LLTools provides approximate string matching, author recognition and graph-based methods for identifying and linking different instances of the same real-world entity. We show through two applications that LLTools can be used to rapidly create and train research prototypes for human language processing.