Miracle-dz/UniFAR-FTUs huggingface dataset:
ASC Induces Apoptosis via Activation of Caspase-9 by Enhancing Gap Junction-Mediated Intercellular Communication

ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression. The effects of ASC were examined using in vitro cell cultures based on comparisons between low and high cell density conditions as well as in a xenograft murine model. ASC overexpression was established by insertion of the ASC gene into pcDNA3 and pMX-IRES-GFP vectors, the latter being packed into a retrovirus and subjected to reproducible competitive assays using parental cells as an internal control, for evaluation of cell viability. p21 and p53 were silenced using shRNA. Cell viability was suppressed in ASC-expressing transfectants as compared with control cells at high cell density conditions in in vitro culture and colony formation assays and in in vivo ectopic tumor formation trials. This suppression was not detected in low cell density conditions. Furthermore, remarkable progression of apoptosis was observed in ASC-introduced cells at a high cell density, but not at a low one. ASC-dependent apoptosis was mediated not by p21, p53, or caspase-1, but rather by cleavage of caspase-9 as well as by suppression of the NF-κB-related X-linked inhibitor-of-apoptosis protein. Caspase-9 cleavage was observed to be dependent on gap junction formation. The remarkable effect of ASC on the induction of apoptosis through caspase-9 and gap junctions revealed in this study may lead to promising new approaches in anticancer therapy.
Executive Compensation and Managerial Risk-Taking

This paper provides empirical evidence of a strong relation between the structure of managerial compensation and both investment policy and debt policy. Higher sensitivity of CEO wealth to stock volatility (vega) is associated with riskier policy choices, including relatively more investment in R&D, more focus on fewer lines of business, and higher leverage. These results are consistent with the hypothesis that higher vega in the managerial compensation scheme gives executives the incentive to implement policy choices that increase risk. Our results also indicate that these investment and financial policy choices are among the primary mechanisms through which vega affects stock price volatility.
Dissociative Effects of Methylphenidate in Nonhuman Primates: Trade-offs between Cognitive and Behavioral Performance

Low doses of methylphenidate reduce hyperactivity and improve attention in individuals with attention deficit hyperactivity disorder (ADHD) as well as in healthy humans and animals. Despite its extensive use, relatively little is known about its mechanisms of action. This study investigated the effects of methylphenidate on working memory performance, impulsivity, response accuracy and precision, and the ability to stay on task in rhesus monkeys using an oculomotor delayed response task. Methylphenidate affected task performance in an inverted-U manner in all three subjects tested. The improvements resulted from a reduction in premature responses and, importantly, not from improvement in the memory of target location. The length of time subjects participated in each session was also affected dose dependently. However, the dose at which the length of participation was maximally increased significantly impaired performance on the working memory task. This dissociation of effects has implications for the treatment of ADHD, for the nonprescription use of methylphenidate for cognitive enhancement, and for furthering the basic understanding of the neural substrate underlying these processes.
BRAIN FUNCTIONAL CONNECTIVITY IN CEREBRAL AMYLOID ANGIOPATHY , AN AGE-RELATED CEREBROVASCULAR DISEASE

here is growing evidence that in the aging process both the neural and the vascular aspects of brain function are affected. On the neural side, aging is associated with damage to the myelin sheaths and reduction in the total number of nerve fibers, resulting in a reduction in structural connectivity [1]. But connections in the brain are not only structural (i.e. synapses, axons, etc.); equally important are blood flow related (vascular) connections. This hypothesis arose after the first observation that blood flow increased and decreased simultaneously in the two motor regions in opposite brain hemispheres. We call regions such as these functionally connected. As we get older, so does our brain’s vascular system: the elasticity of small blood vessels in the brain diminishes in some persons [2] and white matter lesions of presumed vascular origin increase [3]. These vascular changes affect blood flow to neurons and thus may reduce functional connectivity. The extent to which these vascular-related phenomena contribute to age-related reductions in structural or functional connectivity (and perhaps to cognitive decline) is not yet clear.
Topological Alterations of the Intrinsic Brain Network in Patients with Functional Dyspepsia

Background/Aims Previous studies reported that integrated information in the brain ultimately determines the subjective experience of patients with chronic pain, but how the information is integrated in the brain connectome of functional dyspepsia (FD) patients remains largely unclear. The study aimed to quantify the topological changes of the brain network in FD patients. Methods Small-world properties, network efficiency and nodal centrality were utilized to measure the changes in topological architecture in 25 FD patients and 25 healthy controls based on functional magnetic resonance imaging. Pearson’s correlation assessed the relationship of each topological property with clinical symptoms. Results FD patients showed an increase of clustering coefficients and local efficiency relative to controls from the perspective of a whole network as well as elevated nodal centrality in the right orbital part of the inferior frontal gyrus, left anterior cingulate gyrus and left hippocampus, and decreased nodal centrality in the right posterior cingulate gyrus, left cuneus, right putamen, left middle occipital gyrus and right inferior occipital gyrus. Moreover, the centrality in the anterior cingulate gyrus was significantly associated with symptom severity and duration in FD patients. Nevertheless, the inclusion of anxiety and depression scores as covariates erased the group differences in nodal centralities in the orbital part of the inferior frontal gyrus and hippocampus. Conclusions The results suggest topological disruption of the functional brain networks in FD patients, presumably in response to disturbances of sensory information integrated with emotion, memory, pain modulation, and selective attention in patients.
Delivering better government

This paper critically examines the Irish Government’s commitment to “Delivering better government”, in the context of achieving gender equality. The strategic management initiative (SMI) seeks highest quality of service delivery to customers in a modern flexible and professional manner. This necessitates the fullest development of human resources. To achieve this end a study was undertaken to investigate gender imbalance at managerial grades. The report highlighted continuing gender imbalance at all grades and a prevailing culture that is less than conducive to women and many men. The authors called for a new strategic approach to gender equality in which specific targets are set over a specific time frame. The Irish Civil Service is now faced with a combined need to address a new equality agenda in order to deliver its strategic vision of quality in serving the public, thereby underpinning the need to pursue quality, equality and diversity as core values in a fast‐growing Irish economy.
Majorize-Minimize Algorithm for Multiresponse Sparse Regression

Multiresponse sparse regression is the problem of estimating many response variables using a common subset of input variables. Our model is linear, so row sparsity of the coefficient matrix implies subset selection. This is formulated as the problem of minimizing the residual sum of squares, where the row norms of the coefficient matrix are penalized. The proposed approach differs from existing ones in that any penalty function that is increasing, differentiable, and concave can be used. A convergent majorize-minimize algorithm is adopted for minimization. We also propose an active set strategy for tracking the nonzero rows of the coefficient matrix when the minimization is performed for a sequence of descending values of the penalty parameter. Numerical experiments are given to illustrate the active set strategy and analyze penalization with different degrees of concavity.
Targeting EMP3 suppresses proliferation and invasion of hepatocellular carcinoma cells through inactivation of PI3K/Akt pathway

Epithelial membrane protein-3 (EMP3), a typical member of the epithelial membrane protein (EMP) family, is epigenetically silenced in some cancer types, and has been proposed to be a tumor suppressor gene. However, its effects on tumor suppression are controversial and its roles in development and malignancy of hepatocellular carcinoma (HCC) remain unclear. In the present study, we found that EMP3 was highly expressed in the tumorous tissues comparing to the matched normal tissues, and negatively correlated with differentiated degree of HCC patients. Knockdown of EMP3 significantly reduced cell proliferation, arrested cell cycle at G1 phase, and inhibited the motility and invasiveness in accordance with the decreased expression and activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) in HCC cells. The in vivo tumor growth of HCC was effectively suppressed by knockdown of EMP3 in a xenograft mouse model. The EMP3 knockdown-reduced cell proliferation and invasion were attenuated by inhibition of phosphatidylinositol 3-kinase (PI3K) or knockdown of Akt, and rescued by overexpression of Akt in HCC cells. Clinical positive correlations of EMP3 with p85 regulatory subunit of PI3K, p-Akt, uPA, as well as MMP-9 were observed in the tissue sections from HCC patients. Here, we elucidated the tumor progressive effects of EMP3 through PI3K/Akt pathway and uPA/MMP-9 cascade in HCC cells. The findings provided a new insight into EMP3, which might be a potential molecular target for diagnosis and treatment of HCC.
Quality of service over Ethernet for telelearning applications

The objective of this investigation is to implement a technology that provides measurements of quality of service (QoS) of established local area networks. Improvements of the required infrastructure for applications of telelearning (videoconference, electronic blackboard, shared applications&hellip;) are implemented with a minimal cost. We are implementing features of ATM on Ethernet local area networks, through the protocol "Cells In Frame" (CIF). This protocol encapsulates ATM cells in Ethernet frames using CIF specification. Values of measured parameters reveal that the implementation provides the ATM quality of service necessary for telelearning traffic type.
Krüppel-like factor 4 promotes human osteosarcoma growth and metastasis via regulating CRYAB expression

Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is an essential regulator in many cellular processes, including differentiation, proliferation, inflammation, pluripotency, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has been reported as a tumor suppressor or an oncogene in many cancers. However, the role of KLF4 in osteosarcoma is largely unknown. Here we found the expression of KLF4 was significantly increased in human osteosarcoma tissues compared with the normal tissues. Elevated KLF4 promoted human osteosarcoma cell proliferation and metastasis. Subsequently, mechanistic studies revealed KLF4 specifically bound the promoter of CRYAB and upregulated CRYAB expression in human osteosarcoma cells. Moreover, we found that KLF4 enhanced osteosarcoma cell proliferation and migration via upregulating CRYAB. Therefore, our studies suggested KLF4 may be a potential target for human osteosarcoma therapy.
Diversity of sessile rotifers (Gnesiotrocha, Monogononta, Rotifera) in Thale Noi Lake, Thailand

In response to a clear gap in knowledge on the biodiversity of sessile Gnesiotrocha rotifers at both global as well as regional Southeast Asian scales, we performed a study of free-living colonial and epiphytic rotifers attached to fifteen aquatic plant species in Thale Noi Lake, the first Ramsar site in Thailand. We identified 44 different taxa of sessile rotifers, including thirty-nine fixosessile species and three planktonic colonial species. This corresponds with about 40 % of the global sessile rotifer diversity, and is the highest alpha-diversity of the group ever recorded from a single lake. The record further includes a new genus, Lacinularoides n. gen., containing a single species L. coloniensis (Colledge, 1918) n. comb. , which is redescribed, and several possibly new species, one of which, Ptygura thalenoiensis n. spec. is formally described here. Ptygura noodti (Koste, 1972) n. comb. is relocated from Floscularia, based on observations of living specimens of this species, formerly known only from preserved, contracted specimens from the Amazon region. In addition, ten of the species recorded are added to the fauna of the Oriental region, twenty-seven are new to Thailand.
Development and Efficacy of a Frequent-Word Auditory Training Protocol for Older Adults with Impaired Hearing

Objectives: The objective of this study was to evaluate the efficacy of a word-based auditory-training procedure for use with older adults who have impaired hearing. The emphasis during training and assessment is placed on words with a high frequency of occurrence in American English. Design: In this study, a repeated-measures group design was used with each of the two groups of participants to evaluate the effects of the word-based training regimen. One group comprised 20 young adults with normal hearing and the other consisted of 16 older adults with impaired hearing. The group of young adults was not included for the purpose of between-group comparisons. Rather, it was included to demonstrate the efficacy of the training regimen, should efficacy fail to be demonstrated in the group of older adults, and to estimate the magnitude of the benefits that could be achieved in younger listeners. Results: Significant improvements were observed in the group means for each of five measures of post-training assessment. Pretraining and post-training performance assessments were all based on the open-set recognition of speech in a fluctuating speech-like background noise. Assessment measures ranged from recognition of trained words and phrases produced by talkers heard during training to the recognition of untrained sentences produced by a talker not encountered during training. In addition to these group data, analysis of individual data via 95% critical differences for each assessment measure revealed that 75 to 80% of the older adults demonstrated significant improvements on most or all of the post-training measures. Conclusions: The word-based auditory-training program examined here, one based on words having a high frequency of occurrence in American English, has been demonstrated to be efficacious in older adults with impaired hearing. Training on frequent words and frequent phrases generalized to sentences constructed from frequently occurring words whether spoken by talkers heard during training or by a novel talker.
The Prognostic Value of Enhanced-MRI and Fluoroscopic Factors for Predicting the Effects of Transforaminal Steroid Injections on Lumbosacral Radiating Pain

Objective To investigate the predictive value of enhanced-magnetic resonance imaging (MRI) and fluoroscopic factors regarding the effects of transforaminal epidural steroid injections (TFESIs) in low back pain (LBP) patients with lumbosacral radiating pain. Methods A total of 51 patients who had LBP with radiating pain were recruited between January 2011 and December 2012. The patient data were classified into the two groups ‘favorable group’ and ‘non-favorable group’ after 2 weeks of follow-up results. The favorable group was defined as those with a 50%, or more, reduction of pain severity according to the visual analogue scale (VAS) for back or leg pain. The clinical and radiological data were collected for univariate and multivariate analyses to determine the predictors of the effectiveness of TFESIs between the two groups. Results According to the back or the leg favorable-VAS group, the univariate analysis revealed that the corticosteroid approach for the enhanced nerve root, the proportion of the proximal flow, and the contrast dispersion of epidurography are respectively statistically significant relative to the other factors. Lastly, the multiple logistic regression analysis showed a significant association between the corticosteroid approach and the enhanced nerve root in the favorable VAS group. Conclusion Among the variables, MRI showed that the corticosteroid approach for the enhanced target root is the most important prognostic factor in the predicting of the clinical parameters of the favorable TFESIs group.
Functional and Structural Adaptations of Coronary Microvessels Distal to a Chronic Coronary Artery Stenosis

Distal to a chronic coronary artery stenosis, structural remodeling of the microvasculature occurs. The microvascular functional changes distal to the stenosis have not been studied in detail. We tested the hypothesis that microvascular structural remodeling is accompanied by altered regulation of coronary vasomotor tone with increased responsiveness to endothelin-1. Vasomotor tone was studied in coronary microvessels from healthy control swine and from swine 3 to 4 months after implantation of an occluder that causes a progressive coronary narrowing, resulting in regional left ventricular dysfunction and blunted myocardial vasodilator reserve. Arterioles (≈200-&mgr;m passive inner diameter at 60 mm Hg) were isolated from regions perfused by the stenotic left anterior descending and normal left circumflex coronary arteries and studied in vitro. Passive pressure–diameter curves demonstrated reduced distensibility of subendocardial left anterior descending compared with subendocardial left circumflex or control arterioles, suggestive of structural remodeling. Myogenic responses were blunted in subendocardial left anterior descending compared with left circumflex arterioles, reflecting altered smooth muscle function. However, vasodilator responses to nitroprusside and bradykinin were not different in the endocardium, suggesting preserved endothelium and smooth muscle responsiveness. Finally, vasoconstrictor responses to endothelin-1 were enhanced in left anterior descending arterioles compared with left circumflex or control arterioles. Regional myocardial vascular conductance responses to bradykinin and endothelin in vivo confirmed the in vitro observations. In conclusion, inward remodeling of coronary microvessels distal to a stenosis is accompanied by exaggerated vasoconstrictor responses to endothelin-1. These structural and functional alterations may aggravate flow abnormalities distal to a chronic coronary artery stenosis.
Role of Self-Generated Odor Cues in Contextual Representation

As first demonstrated in the patient H.M. , the hippocampus is critically involved in forming episodic memories, the recall of “what” happened “where” and “when. ” In rodents, the clearest functional correlate of hippocampal primary neurons is the place field: a cell fires predominantly when the animal is in a specific part of the environment, typically defined relative to the available visuospatial cues. However, rodents have relatively poor visual acuity. Furthermore, they are highly adept at navigating in total darkness. This raises the question of how other sensory modalities might contribute to a hippocampal representation of an environment. Rodents have a highly developed olfactory system, suggesting that cues such as odor trails may be important. To test this, we familiarized mice to a visually cued environment over a number of days while maintaining odor cues. During familiarization, self‐generated odor cues unique to each animal were collected by re‐using absorbent paperboard flooring from one session to the next. Visual and odor cues were then put in conflict by counter‐rotating the recording arena and the flooring. Perhaps surprisingly, place fields seemed to follow the visual cue rotation exclusively, raising the question of whether olfactory cues have any influence at all on a hippocampal spatial representation. However, subsequent removal of the familiar, self‐generated odor cues severely disrupted both long‐term stability and rotation to visual cues in a novel environment. Our data suggest that odor cues, in the absence of additional rule learning, do not provide a discriminative spatial signal that anchors place fields. Such cues do, however, become integral to the context over time and exert a powerful influence on the stability of its hippocampal representation. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Deficiency of Glutathione Transferase Zeta Causes Oxidative Stress and Activation of Antioxidant Response Pathways

Glutathione S-transferase (GST) zeta (GSTZ1-1) plays a significant role in the catabolism of phenylalanine and tyrosine, and a deficiency of GSTZ1-1 results in the accumulation of maleylacetoacetate and its derivatives maleylacetone (MA) and succinylacetone. Induction of GST subunits was detected in the liver of Gstz1–/– mice by Western blotting with specific antisera and high-performance liquid chromatography analysis of glutathione affinity column-purified proteins. The greatest induction was observed in members of the mu class. Induction of NAD(P)H:quinone oxidoreductase 1 and the catalytic and modifier subunits of glutamate-cysteine ligase was also observed. Many of the enzymes that are induced in Gstz1–/– mice are regulated by antioxidant response elements that respond to oxidative stress via the Keap1/Nrf2 pathway. It is significant that diminished glutathione concentrations were also observed in the liver of Gstz1–/– mice, which supports the conclusion that under normal dietary conditions, the accumulation of electrophilic intermediates such as maleylacetoacetate and MA results in a high level of oxidative stress. Elevated GST activities in the livers of Gstz1–/– mice suggest that GSTZ1-1 deficiency may alter the metabolism of some drugs and xenobiotics. Gstz1–/– mice given acetaminophen demonstrated increased hepatotoxicity compared with wild-type mice. This toxicity may be attributed to the increased GST activity or the decreased hepatic concentrations of glutathione, or both. Patients with acquired deficiency of GSTZ1-1 caused by therapeutic exposure to dichloroacetic acid for the clinical treatment of lactic acidosis may be at increased risk of drug- and chemical-induced toxicity.
ON GLOBAL APPROXIMATION PROPERTIES OF ABSTRACT INTEGRAL OPERATORS IN ORLICZ SPACES AND APPLICATIONS

In this paper we study approximation properties for the class of general integral operators of the form (Twf)(s) = ∫ Hw Kw(s, t, f(t))dμHw(t) s ∈ G, w > 0 whereG is a locally compact Hausdorff topological space, (Hw)w>0 is a net of closed subsets of G with suitable properties and, for every w > 0, μHw is a regular measure on Hw. We give pointwise, uniform and modular convergence theorems in abstract modular spaces and we apply the results to some kinds of discrete operators including the sampling type series.