Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Sensitivity of Leukemia Cells to Propranolol

Background Propranolol, as a beta-adrenergic blocker is used for treatment of a large number of cardiovascular diseases such as hypertension and arrhythmias. The inhibitory effects of propranolol on tumor cells growth and also its cytotoxicity on cancerous cells have been revealed by several studies. In this study the sensitivity of a number of human leukemic cell lines to propranolol was evaluated in vitro. Methods Two human leukemic T cells (Molt-4 and Jurkat) and a monocyte (U937) cell line were used in this study. The cells were cultured in complete RPMI medium and then incubated with different concentrations of propranolol (0.0004 -0.4 mM) in the presence or absence of phytoheamagglutinin (20 μg/ml) for 12, 24 and 48 hours. The cytotoxic effect of the drug was then assessed by trypan blue dye exclusion and also 3-(4,5-dimethyl thiazol-2,5-diphenyltetrazoliumbromide) (MTT) reduction methods. Results Propranolol induced a significant dose dependent cytotoxic effect at ≥ 0.2 mM concentration on all three human cell lines (Molt-4, Jurkat and U937) used in this study, after 12 hours incubation onwards, compared to untreated control cells. Conclusions Our results demonstrated that leukemic cell lines used in this study were sensitive to propranolol at ≥ 0.2 mM concentration of the drug. These results suggest that propranolol may have potential implication in chemoprevention of lymphoproliferative disorders along with its chronic long-term usage in cardiac problems. Keywords Propranolol; Leukemia; Cell lines; Sensitivity
A novel role for RAD54: this host protein modulates geminiviral DNA replication

Geminiviruses primarily encode only few factors, such as replication initiator protein (Rep), and need various host cellular machineries for rolling‐circle replication (RCR) and/or recombination‐dependent replication (RDR). We have identified a host factor, RAD54, in a screen for Rep‐interacting partners and observed its role in DNA replication of the geminivirus mungbean yellow mosaic India virus (MYMIV). We identified the interacting domains ScRAD54 and MYMIV‐Rep and observed that ScRAD54 enhanced MYMIV‐Rep nicking, ATPase, and helicase activities. An in vitro replication assay demonstrated that the geminiviral DNA replication reaction depends on the viral Rep protein, viral origin of replication sequences, and host cell‐cycle proteins. Rad54‐deficient yeast nuclear extract did not support in vitro viral DNA replication, while exogenous addition of the purified ScRAD54 protein enhanced replication. The role of RAD54 in in planta replication was confirmed by the transient replication assay; i.e., agroinoculation studies. RAD54 is a well‐known recombination/repair protein that uses its DNA‐dependent ATPase activity in conjunction with several other host factors. However, this study demonstrates for the first time that the eukaryotic rolling‐circle replicon depends on the RAD54 protein. — Kaliappan, K. , Choudhury, N. R. , Suyal, G. , Mukherjee, S. K. A novel role for RAD54: this host protein modulates geminiviral DNA replication. FASEB J. 26, 1142‐1160 (2012). www.fasebj. org
Absence of Long-Wavelength Photic Potentiation of Murine Intrinsically Photosensitive Retinal Ganglion Cell Firing In Vitro

Melanopsin is an opsin-family photopigment required for photosensitivity of the intrinsically photosensitive retinal ganglion cells (ipRGCs), which subserve photic entrainment of circadian rhythms in mammals. The melanopsin photocycle is presently unknown but is independent of the enzymatic photocycle employed by rhodopsin and cone opsins. Recent experiments have demonstrated that red-light exposure potentiates circadian phase-shifting responses to blue-light stimuli, consistent with the hypothesis that melanopsin functions as a bistable photopigment. To further test this hypothesis, we analyzed ipRGC firing activity in response to 480-nm blue light with or without intervening long-wavelength 620-nm red-light stimulation, using in vitro multielectrode array recording of postnatal day 8 to 10 murine retina. Cell-firing responses to 480-nm light were highly reproducible. No significant potentiating or bleaching effect of intervening subthreshold 620-nm light on ipRGC firing to 480-nm light could be discerned. Further physiologic and biochemical analysis of the ipRGC photoreception is required to reconcile the presence of long-wavelength potentiation at the level of the SCN with its absence in light-induced ipRGC firing.
Control of KirBac3.1 Potassium Channel Gating at the Interface between Cytoplasmic Domains*

Background: KirBac3.1 is a prokaryotic homolog of eukaryotic Kir channels. Results: A high-resolution crystal structure of a mutant channel reveals a novel open conformation. Conclusion: The intersubunit interface between the cytoplasmic domains controls channel gating. Significance: These findings help define the structures important for gating in prokaryotic and eukaryotic Kir channels. KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures of KirBac3.1 have provided important insights into the structural basis of gating in Kir channels. In this study, we demonstrate that KirBac3.1 channel activity is strongly pH-dependent, and we used x-ray crystallography to determine the structural changes that arise from an activatory mutation (S205L) located in the cytoplasmic domain (CTD). This mutation stabilizes a novel energetically favorable open conformation in which changes at the intersubunit interface in the CTD also alter the electrostatic potential of the inner cytoplasmic cavity. These results provide a structural explanation for the activatory effect of this mutation and provide a greater insight into the role of the CTD in Kir channel gating.
Resistance characterization of flip chip joint formed using Au bumps and anisotropic conductive adhesives

In this paper, the resistance characterization of flip chip joints formed using Au bumps and anisotropic conductive adhesives (ACAs) is reported. A flip chip on glass (FCOG) test vehicle with indium tin oxide (ITO) conductive lines was used to study the effect of Au bump structure, bonding forces, bump size, conductive filler size and conductive filler loading on contact resistance. Both anisotropic conductive film (ACF) and anisotropic conductive paste (ACP) with varying filler sizes and filler loadings were used to assemble the FCOG test vehicle. Joint contact resistances were obtained by a 4-point measurement method. Results showed that ACP joints generally requires an order of magnitude lower bonding force than ACF joints to achieve consistent contact resistance values. Uncoined Au bumps are preferred for ACF and ACP joints because they offer lower contact resistance than coined Au bumps. This work has led to a better understanding of contact resistance in ACF and ACP joints.
Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma

Circulating microRNAs, present either in the cellular component, peripheral blood mononuclear cells (PBMC), or in cell-free plasma, have emerged as biomarkers for age-dependent systemic, disease-associated changes in many organs. Previously, we have shown that microRNA (miR)-34a is increased in circulating PBMC of Alzheimer's disease (AD) patients. In the present study, we show that this microRNA's sister, miR-34c, exhibits even greater increase in both cellular and plasma components of AD circulating blood samples, compared to normal age-matched controls. Statistical analysis shows the accuracy of levels of miR-34c assayed by receiver operating characteristic (ROC) analysis: the area under the curve is 0.99 (p < 0.0001) and the 95% confidence level extends from 0.97 to 1. Pearson correlation between miR-34c levels and mild and moderate AD, as defined by the mini-mental state examination (MMSE), shows an r-value of −0.7, suggesting a relatively strong inverse relationship between the two parameters. These data show that plasma levels of microRNA 34c are much more prominent in AD than those of its sister, miR-34a, or than its own level in PBMC. Transfection studies show that miR-34c, as does its sister miR-34a, represses the expression of several selected genes involved in cell survival and oxidative defense pathways, such as Bcl2, SIRT1, and others, in cultured cells. Taken together, our results indicate that increased levels of miR-34c in both PBMC and plasma may reflect changes in circulating blood samples in AD patients, compared to age-matched normal controls.
Co-clustering by similarity refinement

When a data set contains objects of multiple types, to cluster the objects of one type, it is often necessary to consider the cluster structure on the objects of the other types. Co-clustering the related objects often generates better clusters. One basic connection here is that the similarity among the objects of one type is often affected by the cluster structures on the objects of the other types. Although many co-clustering schemes have been proposed, none has explicitly explored such a connection. We propose a framework that utilizes this connection directly. In this framework, employing a spectral-embedding- based approach, we first obtain certain approximate cluster information about the objects of individual types. Such information is then used to refine the similarity measures for the objects of the related types. The final clustering is performed with the refined similarity. We tested our framework on both bipartite-graph and document clustering. Our experiments showed that the refined similarity leads to much better clustering, indicating that our refinement makes the similarity measures closer to their true values.
Probing nuclear pore complex architecture with proximity-dependent biotinylation

Significance Proximity-dependent biotinylation (BioID) is a readily accessible method for identifying protein associations that occur in living cells. Fusion of a promiscuous biotin ligase to a bait protein for expression in live cells enables covalent biotin labeling, and thus identification, of proteins proximate to the bait. Here we used BioID to probe the organization of the nuclear pore complex, a large structure that regulates molecular transport between the nucleus and cytoplasm. These studies enhance our understanding of major subcomplexes within the nuclear pore complex and demonstrate the utility of BioID for studying the organization of large protein assemblies. Additionally, we have measured the labeling radius of BioID, thus enabling the rational application of this method and more meaningful data interpretation. Proximity-dependent biotin identification (BioID) is a method for identifying protein associations that occur in vivo. By fusing a promiscuous biotin ligase to a protein of interest expressed in living cells, BioID permits the labeling of proximate proteins during a defined labeling period. In this study we used BioID to study the human nuclear pore complex (NPC), one of the largest macromolecular assemblies in eukaryotes. Anchored within the nuclear envelope, NPCs mediate the nucleocytoplasmic trafficking of numerous cellular components. We applied BioID to constituents of the Nup107–160 complex and the Nup93 complex, two conserved NPC subcomplexes. A strikingly different set of NPC constituents was detected depending on the position of these BioID-fusion proteins within the NPC. By applying BioID to several constituents located throughout the extremely stable Nup107–160 subcomplex, we refined our understanding of this highly conserved subcomplex, in part by demonstrating a direct interaction of Nup43 with Nup85. Furthermore, by using the extremely stable Nup107–160 structure as a molecular ruler, we defined the practical labeling radius of BioID. These studies further our understanding of human NPC organization and demonstrate that BioID is a valuable tool for exploring the constituency and organization of large protein assemblies in living cells.
Age Trends of Early Awakening and Feeling Worse in the Morning Than in the Evening in Apparently Normal People

Age-specific prevalences of early awakening and feeling worse in the morning than in the evening were studied in 6034 subjects (schoolchildren, students, and employees) aged 9 to 60 years. Early awakening was found to be significantly more prevalent in males at most ages. In both sexes, early awakening was least prevalent in subjects aged 13 to 26 years and feeling worse in the morning than in the evening was most prevalent in subjects in their 20s. In subjects older than 21 years, the age trend of early awakening was a uniform increase, while that of feeling worse in the morning than in the evening was a uniform decrease. These two symptoms show roughly opposite age trends. Increasing prevalence of early awakening with age in endogenous depressives can be viewed at least partly as a reflection of the normal aging process.
Regulation of apical K and Na channels and Na/K pumps in rat cortical collecting tubule by dietary K

The patch-clamp technique was used to study the properties and the density of conducting K and Na channels in the apical membrane of rat cortical collecting tubule. The predominant K channel observed in cell- attached patches (SK channels) had an outward single-channel conductance (with LiCl in the pipette) of 10 pS. The inward conductance (with KCl in the pipette) was 42 pS. The channel had a high open probability that increased with depolarization. Kinetic analysis indicated the presence of a single open state and two closed states. Increasing K intake by maintaining animals on a high K diet for 12-16 d increased the number of SK channels per patch by threefold (0.7- 2.0/patch) over control levels. In addition, conducting Na-selective channels, which were not observed in control animals, were seen at low density (0.5/patch). These channels had properties similar to those observed when the animals were on a low Na diet, except that the mean open probability (0.84) was higher. In other experiments, the whole- cell patch clamp technique was used to measure Na channel activity (as amiloride-sensitive current, INa) and Na pump activity (as ouabain- sensitive current, Ipump). In animals on a high K diet, INa was greater than in controls but much less than in rats on a low Na diet. Ipump was greater after K loading than in controls or Na-depleted animals. These K diet-dependent effects were not accompanied by a significant increase in plasma aldosterone concentrations. To further investigate the relationship between K channel activity and mineralocorticoids, rats were maintained on a low Na diet to increase endogenous aldosterone secretion. Under these conditions, no increase in SK channel density was observed, although there was a large increase in the number of Na channels (to 2.7/patch). Aldosterone was also administered exogenously through osmotic minipumps. As with the low Na diet, there was no change in the density of conducting SK channels, although Na channel activity was induced. These results suggest that SK channels, Na channels and Na/K pumps are regulated during changes in K intake by factors other than aldosterone.
Go With the Flow: Effects of Transparency and User Control on Targeted Advertising Using Flow Charts

Targeted advertising reaches users based on various traits, such as demographics or behaviour. However, users are often reluctant to accept ads. We hypothesise that users are more open to targeted advertising if they can inspect, control and thereby understand the process of ad selection. We conducted a between-subjects study (N=200) to investigate to what extent four key aspects of ads (Quality, Behavioural Intention, Understanding and Attitude) may be affected by transparency and user control using a flow chart. Our results indicate that positive effects of flow charts reported from other domains may also be applicable to advertising: Using flow charts to provide transparency together with user control is found to have more positive effects on domain-specific quality measures than established, text-based approaches and using either of the techniques in isolation. The paper concludes with recommendations for practitioners aiming to improve user response to ads.
Rapid Emergency Medicine Score (REMS) in the trauma population: a retrospective study

Objective Rapid Emergency Medicine Score (REMS) is an attenuated version of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and has utility in predicting mortality in non-surgical patients, but has yet to be tested among the trauma population. The objective was to evaluate REMS as a risk stratification tool for predicting in-hospital mortality in traumatically injured patients and to compare REMS accuracy in predicting mortality to existing trauma scores, including the Revised Trauma Score (RTS), Injury Severity Score (ISS) and Shock Index (SI). Design and setting Retrospective chart review of the trauma registry from an urban academic American College of Surgeons (ACS) level 1 trauma centre. Participants 3680 patients with trauma aged 14 years and older admitted to the hospital over a 4-year period. Patients transferred from other hospitals were excluded from the study as were those who suffered from burn or drowning-related injuries. Patients with vital sign documentation insufficient to calculate an REMS score were also excluded. Primary outcome measures The predictive ability of REMS was evaluated using ORs for in-hospital mortality. The discriminate power of REMS, RTS, ISS and SI was compared using the area under the receiver operating characteristic curve. Results Higher REMS was associated with increased mortality (p<0.0001). An increase of 1 point in the 26-point REMS scale was associated with an OR of 1.51 for in-hospital death (95% CI 1.45 to 1.58). REMS (area under the curve (AUC) 0.91±0.02) was found to be similar to RTS (AUC 0.89±0.04) and superior to ISS (AUC 0.87±0.01) and SI (AUC 0.55±0.31) in predicting in-hospital mortality. Conclusions In the trauma population, REMS appears to be a simple, accurate predictor of in-hospital mortality. While REMS performed similarly to RTS in predicting mortality, it did outperform other traditionally used trauma scoring systems, specifically ISS and SI.
Expression of HMGI‐C, a member of the high mobility group protein family, in a subset of breast cancers: Relationship to histologic grade

The high‐mobility‐group (HMG) protein gene HMGI‐C is apparently involved in the genesis of a variety of benign human solid tumors with rearrangements of chromosomal region 12q14‐15 affecting the HMGI‐C gene. So far, no expression of HMGI‐C has been found in adult tissues, and no data are available on the expression of HMGI‐C in primary human malignant tumors of epithelial origin. Therefore, we analysed the HMGI‐C expression patterns in 44 breast cancer samples and 13 samples of nonmalignant adjacent tissue by hemi‐nested reverse transcriptase–polymerase chain reaction for HMGI‐C expression. There was no detectable expression of HMGI‐C in any nonmalignant adjacent breast tissues analyzed. In contrast, we found expression in 20 of 44 breast cancer samples investigated. In invasive ductal tumors, expression was noted predominantly in tumors with high histologic grade: 17 of 21 breast cancer samples with histologic grade 3 but only three of 16 samples with histologic grades 1 or 2 showed expression of HMGI‐C. In addition, all seven lobular breast cancer samples tested did not express HMGI‐C. From these results, we concluded that HMGI‐ C expression may be of pathogenetic or prognostic importance in breast cancer. Mol. Carcinog. 19:153–156, 1997. © 1997 Wiley‐Liss, Inc.
Geoelectric mapping and characterization of limestone deposits of Ewekoro formation, southwestern Nigeria

62 vertical electrical soundings (VES) were carried out to map limestone deposits of Ewekoro formation, south-western Nigeria. The maximum current electrode spacing AB/2 was 1 km. The results revealed the occurrence of limestone in all the locations within the third and fourth geoelectric layers with resistivity values ranging from 10 to 100 KWm and thickness range of 15 to 90 m. The resistivity values of the limestone samples collected from the study site were also analyzed by laboratory direct method. This direct method revealed that the resistivity values fall within 6 and 171 KWm. The two approaches showed a good degree of correlation in the resistivity value of the limestone and their varying qualities. This research work further showed the occurrence of vast deposit of limestone, which can be of economic importance in mining and industrial purposes. Key words: Resistivity, limestone, geoelectric layer, permeability, Ewekoro formation.
Wetting and Wicking in Fibrous Materials

Abstract This issue reviews developments in wetting and wicking of fibrous materials, covering characterization of wetting; wetting and wicking of fibers, filaments, yarns, and fabrics; factors affecting wetting and wicking of fibrous assemblies; mathematical models of wetting and wicking; and application areas of the same.
Discovering bug patterns in JavaScript

JavaScript has become the most popular language used by developers for client and server side programming. The language, however, still lacks proper support in the form of warnings about potential bugs in the code. Most bug finding tools in use today cover bug patterns that are discovered by reading best practices or through developer intuition and anecdotal observation. As such, it is still unclear which bugs happen frequently in practice and which are important for developers to be fixed. We propose a novel semi-automatic technique, called BugAID, for discovering the most prevalent and detectable bug patterns. BugAID is based on unsupervised machine learning using language-construct-based changes distilled from AST differencing of bug fixes in the code. We present a large-scale study of common bug patterns by mining 105K commits from 134 server-side JavaScript projects. We discover 219 bug fixing change types and discuss 13 pervasive bug patterns that occur across multiple projects and can likely be prevented with better tool support. Our findings are useful for improving tools and techniques to prevent common bugs in JavaScript, guiding tool integration for IDEs, and making developers aware of common mistakes involved with programming in JavaScript.
Barriers and Facilitators for Being Physically Active in Patients with Ankylosing Spondylitis: A Cross-sectional Comparative Study.

OBJECTIVES The aims of the present study were to explore the barriers and facilitators for being physically active and the perceived health benefits of physical activity in a group of patients with ankylosing spondylitis (AS), and to compare the findings with those in population controls. METHODS A total of 148 patients and 133 controls were included in a cross-sectional study. Barriers, facilitators and perceived health benefits were registered in a structured interview. RESULTS Patients were significantly more likely to report barriers to being physically active compared with controls (78% versus 58%; p ≤ 0.001). The barriers most frequently reported by patients were pain (48%), stiffness (36%), fatigue (30%) and disability (21%). A similar proportion of patients (62%) and controls (61%) reported that they had the potential to become more physically active (p = 0.12). Time and motivation were the most frequently reported facilitators in both groups. Patients also reported stable disease (15%) and individually adapted physical activity (8%) as facilitators. An equal proportion of patients (96%) and controls (96%) reported that physical activity had a positive effect on their health (p = 0.94). Improved fitness and increased vitality were the most frequently reported health benefits in both groups. Patients also reported greater disease stability (37%) and reduced pain (33%) as benefits. CONCLUSIONS A larger proportion of patients than controls reported barriers to being physically active. In addition to regular barriers, facilitators and health benefits, patients reported that disease-related factors influenced their participation in physical activity.