Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiofilm Activity of GlmU Enzyme Inhibitors against Catheter-Associated Uropathogens

ABSTRACT The colonization of uropathogenic bacteria on urinary catheters resulting in biofilm formation frequently leads to the infection of surrounding tissue and often requires removal of the catheter. Infections associated with biofilms are difficult to treat since they may be more than 1,000 times more resistant to antibiotics than their planktonic counterparts. We have developed an antibiofilm composition comprising an N-acetyl-d-glucosamine-1-phosphate acetyltransferase (GlmU) inhibitor and protamine sulfate, a cationic polypeptide. The antibiofilm activity of GlmU inhibitors, such as iodoacetamide (IDA), N-ethyl maleimide (NEM), and NEM analogs, including N-phenyl maleimide, N,N′-(1,2-phenylene)dimaleimide (oPDM), and N-(1-pyrenyl)maleimide (PyrM), was tested against that of catheter-associated uropathogens. Both IDA and NEM inhibited biofilm formation in Escherichia coli. All NEM analogs showed antibiofilm activity against clinical isolates of E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus epidermidis, and Enterococcus faecalis. The combination of oPDM with protamine sulfate (PS) enhanced its antibiofilm activity and reduced its effective concentration to as low as 12.5 μM. In addition, we found that the in vitro inhibitory activity of oPDM-plus-PS-coated silicone catheters against P. aeruginosa and S. epidermidis colonization was superior to that of catheters coated with silver hydrogel. Confocal scanning laser microscopy further confirmed that the oPDM-plus-PS-coated silicone catheters were almost free from bacterial colonization. Thus, a broad-spectrum antibiofilm composition comprising a GlmU inhibitor and protamine sulfate shows promise for use in anti-infective coatings for medical devices, including urinary catheters.
Use of a spectrophotometric hemoglobin assay to objectively quantify intracerebral hemorrhage in mice.

BACKGROUND AND PURPOSE There is great interest in developing novel anticoagulant or thrombolytic strategies to treat ischemic stroke. However, at present there are limited means to accurately assess the hemorrhagic potential of these agents. The present studies were designed to develop and validate a method to accurately quantify the degree of intracerebral hemorrhage (ICH) in murine models. METHODS In a murine model, ICH was induced by stereotaxic intraparenchymal infusion of collagenase B alone (6 x 10(-6) U; n = 5) or collagenase B followed by intravenous recombinant tissue plasminogen activator (rt-PA) (0.1 mg/kg; n = 6). Controls consisted of either sham surgery with stereotaxic infusion of saline (n = 5) or untreated animals (n = 5). ICH was (1) graded by a scale based on maximal hemorrhage diameter on coronal sections and (2) quantified by a spectrophotometric assay measuring cyanomethemoglobin in chemically reduced extracts of homogenized murine brain. This spectrophotometric assay was validated with the use of known quantities of hemoglobin or autologous blood added to a separate cohort of homogenized brains. With this assay, the degree of hemorrhage after focal middle cerebral artery occlusion/reperfusion was quantified in mice treated with postocclusion high-dose intravenous rt-PA (10 mg/kg; n = 11) and control mice subjected to stroke but treated with physiological saline solution (n = 9). RESULTS Known quantities of hemoglobin or autologous blood added to fresh whole brain tissue homogenates showed a linear relationship between the amount added and optical density (OD) at the absorbance peak of cyanomethemoglobin (r = 1.00 and .98, respectively). When in vivo studies were performed to quantify experimentally induced ICH, animals receiving intracerebral infusion of collagenase B had significantly higher ODs than saline-infused controls (2.1-fold, increase; P = .05). In a middle cerebral artery occlusion and reperfusion model of stroke, administration of rt-PA after reperfusion increased the OD by 1.8-fold compared with animals that received physiological saline solution (P < .001). When the two methods of measuring ICH (visual score and OD) were compared, there was a linear correlation (r = .88). Additional experiments demonstrated that triphenyltetrazolium staining, which is commonly used to stain viable brain tissue, does not interfere with the spectrophotometric quantification of ICH. CONCLUSIONS These data demonstrate that the spectrophotometric assay accurately and reliably quantifies murine ICH. This new method should aid objective assessment of the hemorrhagic risks of novel anticoagulant or thrombolytic strategies to treat stroke and can facilitate quantification of other forms of ICH.
In vivo electrogene transfer of interleukin‐12 inhibits tumor growth and lymph node and lung metastases in mouse mammary carcinomas

Human breast cancer metastasizes mainly to lymph nodes, lungs, liver, and bone; in the majority of cases, it is the development of metastases which leads to death. In order to suppress mammary cancer metastasis, we applied in vivo electrogene transfer (non‐viral method) as a means of interleukin‐12 (IL‐12) gene therapy on highly metastatic murine mammary cancer model.
Combinatorial ECM Arrays Identify Cooperative Roles for Matricellular Proteins in Enhancing the Generation of TH+ Neurons From Human Pluripotent Cells

The development of efficient cell culture strategies for the generation of dopaminergic neurons is an important goal for transplantation-based approaches to treat Parkinson’s disease. To identify extracellular matrix molecules that enhance differentiation and might be used in these cell cultures we have used micro-contact printed arrays on glass slides presenting 190 combinations of 19 extracellular matrix molecules selected on the basis of their expression during embryonic development of the ventral midbrain. Using long-term neuroepithelial stem cells (Lt-NES), this approach identified a number of matricellular proteins that enhanced differentiation, with the combination of Sparc, Sparc-like (Sparc-l1) and Nell2 increasing the number of tyrosine hydroxylase+ neurons derived from Lt-NES cells and, critically for further translation, human pluripotent stem cells.
Early-stage fundraising of university spin-offs: a study through demand-site perspectives

Abstract University spin-offs have increasingly received attention from academia, governments and policy-makers. However, there are only a limited number of studies within the university spin-off context which fully understand the contribution made by the founding team to fundraising, specifically how they use their social networks and capabilities. Employing resource-based theory and social networks approach, this paper examines whether a founding team exploits its social networks and capabilities to signal the value of a university spin-off. Capabilities are analysed through a set of constructs – technology, strategy, human capital, organizational viability and commercial resource – that have been derived from previous literature. The contribution made by social networks is evaluated using three dimensions – structure, governance and content – which form the construct of relationships within a network. Based on data from 181 university spin-offs in Spain, this paper empirically demonstrates that by exploiting social networks a founding team can improve its capabilities which, in turn, enhance its fundraising ability.
Essential characteristics of effective Balint group leadership.

OBJECTIVE Balint work in the United States has suffered from a lack of written material on how Balint group leaders structure and guide group process. This study identified characteristics of effective Balint group leadership by gathering information from experienced Balint leaders. METHODS We used evaluations of the leadership methods used by 21 Balint group leaders assembled at an American Balint Society workshop to pilot test the Society's credentialing process. Free text and rating data from leader evaluation forms were analyzed using qualitative text analysis and factor analysis. We also conducted focus groups. RESULTS Convergence was seen on several characteristics across all sources of data. Effective Balint leaders operate to create a safe environment and move the group toward a new understanding of a specific doctor-patient relationship. Specific leader behaviors include protecting the presenter from interrogation, encouraging open speculation by group members, avoiding premature solutions, and tolerating silence and uncertainty. DISCUSSION Although Balint group leaders rely on behaviors common to other small-group methods, they create a space and purpose markedly different from that seen in other small groups in medical education. Balint group leaders model and create a safe environment for shared, creative speculation and a more empathic experience of the doctor-patient relationship.
Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions

Chronic hyperglycemia and activation of receptor for advanced glycation end products (RAGE) are known risk factors for microvascular disease development in diabetic retinopathy. Thioredoxin‐interacting protein (TXNIP), an endogenous inhibitor of antioxidant thioredoxin (TRX), plays a causative role in diabetes and its vascular complications. Herein we investigate whether HG and RAGE induce inflammation in rat retinal endothelial cells (EC) under diabetic conditions in culture through TXNIP activation and whether epigenetic mechanisms play a role in inflammatory gene expression. We show that RAGE activation by its ligand S100B or HG treatment of retinal EC induces the expression of TXNIP and inflammatory genes such as Cox2, VEGF‐A, and ICAM1. TXNIP silencing by siRNA impedes RAGE and HG effects while stable over‐expression of a cDNA for human TXNIP in EC elevates inflammation. p38 MAPK‐NF‐κB signaling pathway and histone H3 lysine (K) nine modifications are involved in TXNIP‐induced inflammation. Chromatin immunoprecipitation (ChIP) assays reveal that TXNIP over‐expression in EC abolishes H3K9 tri‐methylation, a marker for gene inactivation, and increases H3K9 acetylation, an indicator of gene induction, at proximal Cox2 promoter bearing the NF‐κB‐binding site. These findings have important implications toward understanding the molecular mechanisms of ocular inflammation and endothelial dysfunction in diabetic retinopathy. J. Cell. Physiol. 221: 262–272, 2009. © 2009 Wiley‐Liss, Inc
The cognitive mobile games for older adults - a Chinese user experience study

Cognitive self-rehabilitation lacks updated means and tools. This paper provides a synopsis of novel cognitive recreation game tools, an analysis of their user feedback, as well as potential new ideas for game developers. The purpose of this study was to evaluate the attitudes and user experiences of Chinese elderly people on mobile memory rehabilitation games originally developed in Finland, Europe. Mobile games that require cognitive skills were tested with a test group in a Chinese elderly care home. User feedback was collected by interviews and observations in the game event. The most noteworthy finding was the positive user experience both of the elderly and the nursing staff and the experience of the games being cognitively stimulating. Games also seemed to provide potential for self-rehabilitation and to support social interaction. Also some special characteristics related to the Chinese culture were found in the game trial, although the experiences were surprisingly similar compared to original Finnish trials despite the cultural differences of Finland and China. The results are an encouragement for conducting further testing (on a larger test group, over a longer time) and continuing with the game development for cognitively impaired older adults. These results also encourage further development and testing of welfare technology applications in different cultural environments.
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism

Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-⍰-1,3-galactose (α-gal) injected into humans from the lone star tick (Amblyomma americanum) bite. This study aims at the functional characterization of two tick enzymes, α-D-galactosidase (ADGal) and α-1,4 galactosyltransferase (β-1,4GalT) in α-gal metabolism. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars: GlcNAc, Glc, and Xyl in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their functional role in α-gal metabolism and AGS onset. Silencing of ADGal led to the significant down regulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in ⍰-gal levels in silenced tissues. However, there was no significant difference in the level of ⍰-gal in β-1,4GalT silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal silenced salivary glands. These results provide an insight into the role of α-D galactosidase & β-1,4GalT in tick biology and the probable involvement in the onset of AGS.
Relationship between metabolic and vascular conditions and cognitive decline among older Mexican Americans

Metabolic and vascular conditions have been independently associated with dementia and cognitive decline among older adults, but research on the combined effects that these conditions have on cognitive decline, especially among older Mexican Americans, is lacking. The purpose of this study was to examine the relationship between metabolic and vascular conditions and cognitive decline among older Mexican Americans.
Head shape evolution in monitor lizards (Varanus): interactions between extreme size disparity, phylogeny and ecology

Characterizing patterns of observed current variation, and testing hypotheses concerning the potential drivers of this variation, is fundamental to understanding how morphology evolves. Phylogenetic history, size and ecology are all central components driving the evolution of morphological variation, but only recently have methods become available to tease these aspects apart for particular body structures. Extant monitor lizards (Varanus) have radiated into an incredible range of habitats and display the largest body size range of any terrestrial vertebrate genus. Although their body morphology remains remarkably conservative, they have obvious head shape variation. We use two‐dimensional geometric morphometric techniques to characterize the patterns of dorsal head shape variation in 36 species (375 specimens) of varanid, and test how this variation relates to size, phylogenetic history and ecology as represented by habitat. Interspecific head shape disparity is strongly allometric. Once size effects are removed, principal component analysis shows that most shape variation relates to changes in the snout and head width. Size‐corrected head shape variation has strong phylogenetic signal at a broad level, but habitat use is predictive of shape disparity within phylogenetic lineages. Size often explains shape disparity among organisms; however, the ability to separate size and shape variation using geometric morphometrics has enabled the identification of phylogenetic history and habitat as additional key factors contributing to the evolution of head shape disparity among varanid lizards.
Characterization of multidrug-resistant and metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates from a paediatric clinic in China.

BACKGROUND In the present study, we characterized multidrug-resistant Pseudomonas aeruginosa (MDRP) clinical isolates from a paediatric facility and investigated the types and features of the metallo-beta-lactamases (MBLs) produced by carbapenem-resistant strains. METHODS Four hundred and ninety-eight strains of Pseudomonas aeruginosa were isolated from patients at Beijing Children's Hospital between January 2005 and December 2006. The minimal inhibition concentrations (MICs) of the strains for 13 antibiotics were measured. A combination of the E test and PCR amplification/DNA sequencing was used to define the carbapenem-resistant strains. RESULTS We found that 24.1% (120/498) of the isolates were MDRP. The frequencies of resistance to imipenem and meropenem were 34.2% and 35.8%, respectively, and the MIC50 and MIC90 values for the two antibiotics were identical at 4 microg/ml and 32 microg/ml, respectively. The detection rate for carbapenem resistance was 49.2% (59/120). Among the 59 carbapenem-resistant Pseudomonas aeruginosa strains, 39 (66.1%) were positive for the MBL genotype; 35 (89.7%) strains carried the bla(IMP) gene and 4 (10.3%) strains carried the bla(VIM) gene. Neither bla(SPM) nor bla(GIM) was amplified from any of the 59 isolates. DNA sequencing revealed that IMP-1 was present in 35 IMP-producing isolates and VIM-2 was detected in four VIM-producing isolates. CONCLUSIONS These MDRP isolates exhibited high frequencies of resistance to carbapenems among clinical isolates from a paediatric facility in Beijing, China. The production of MBL appears to be an important mechanism for carbapenem resistance in Pseudomonas aeruginosa.
Sustainability of social security systems in EU countries: Panel cointegration analysis with multiple structural breaks under cross-sectional dependence

In this study, the sustainability of social security policies in EU countries was analyzed by panel data method with multiple structural breaks under cross-sectional dependence for the 1990-2013 periods. The existence of cointegration was tested by Basher and Westerlund (2009) method and series were found to be cointegrated. Cointegration coefficients were estimated by AMG method and it was determined that social security policies are sustainable in a weak form in these countries; when the social security systems’ expenditure is increased by 1%, revenues are increased by 0.86% and revenues of the system cannot compensate the expenses. Austria has the highest rate of sustainability of the social security system while Ireland and Finland have the lowest rates.
Effects of walking on the preservation of bone mineral density in perimenopausal and postmenopausal women: a systematic review and meta-analysis

Objective This study aims to critically evaluate the effects of a walking intervention on bone mineral density (BMD) in perimenopausal and postmenopausal women and to identify the optimal duration of this walking exercise intervention. Methods Two independent reviewers assessed for eligibility randomized and nonrandomized controlled trials evaluating the effects of walking on BMD in perimenopausal and postmenopausal women. Heterogeneity, potential publication bias, and the quality of the included trials were assessed. Results Ten trials were eligible for inclusion. A meta-analysis of trials assessing lumbar spine BMD showed no significant effects (weighted mean difference [WMD] [fixed effects], 0.01 g/cm2; 95% CI, −0.00 to 0.02; P = 0.05) regardless of the length of the intervention duration. BMD at the femoral neck increased after long intervention durations (6 mo to 1-2 y), although no significant effect could be seen when all trials assessing femoral neck BMD were taken into account (WMD [fixed effects], 0.01 g/cm2; 95% CI, −0.00 to 0.01; P = 0.07). The effects of walking on the radius and whole body were not significant (WMD [random effects], −0.01 g/cm2; 95% CI, −0.06 to 0.04; P = 0.71; and WMD [fixed effects], 0.04 g/cm2; 95% CI, −0.00 to 0.08; P = 0.06, respectively). Conclusions Walking as a singular exercise therapy has no significant effects on BMD at the lumbar spine, at the radius, or for the whole body in perimenopausal and postmenopausal women, although significant and positive effects on femoral neck BMD in this population are evident with interventions more than 6 months in duration.
Microinfusions of Flumazenil into the Basolateral but Not the Central Nucleus of the Amygdala Enhance Memory Consolidation in Rats

Extensive evidence indicates that benzodiazepine receptors in the amygdala are involved in regulating memory consolidation. Recent findings indicate that many other drugs and hormones influence memory through selective activation of the basolateral amygdala nucleus (BLA). This experiment examined whether the memory-modulatory effect of flumazenil, a benzodiazepine receptor antagonist, selectively involves the BLA. Bilateral microinfusions of flumazenil (12 nmol in 0.2 microl) into the BLA of rats administered immediately after training in an inhibitory avoidance task significantly enhanced 48-h retention performance whereas infusions into the central nucleus were ineffective. These findings indicate that the BLA is selectively involved in mediating flumazenil's influence on memory storage and are thus consistent with extensive evidence indicating that the BLA is involved in regulating memory consolidation.
Sliding-Mode-Control-Based Robust Finite-Time Antisway Tracking Control of 3-D Overhead Cranes

In this paper, a robust finite-time antisway (i.e., antiswing and antiskew) tracking control method is developed for three-dimensional (3-D) overhead crane systems using a sliding-mode control (SMC) method. In order to control the overhead cranes, various tracking controllers have been developed to achieve satisfactory position tracking and swing suppression. However, along with the trolley and girder positions, both sway angles (i.e., swing and skew angles) should be controlled using the forces driving the trolley and girder for satisfactory transient response and safety enhancement through the suppression of sway angles even in the presence of uncertainties in 3-D cranes that have not been a major consideration in previous works. By introducing the sliding surface dependent on position tracking errors and the finite-time stabilization method for the skew angular rate, the proposed SMC-based robust finite-time antisway tracking control method is designed using the terms, each of which achieves position tracking control, antiswing control, and antiskew control. Accordingly, the proposed method can effectively suppress the sway motion of the 3-D crane and work well even with the variation in payload weight, the initial sway angles, and parameter uncertainties due to the payload weight uncertainty. The validity of the proposed method is supported by stability analysis and simulation and experimental results.
An Extended Reinforcement Learning Framework to Model Cognitive Development With Enactive Pattern Representation

In order to make machines more intelligent, it is inevitable to understand human-like cognitive development, in which adaptive, autonomous and progressive evolution of cognitive decision-making in interacting with the environment plays a key role. Inspired by enactive artificial intelligence and evolutionary sampling learning, a new cognitive development learning model termed evolutionary enactive learning (EEL) is proposed in this paper. The proposed model is constructed by extending the reinforcement learning framework and introducing the utility-selection theory to guide the coevolution of pattern representation and decision-making policies. Theoretical analysis on the model’s validity of EEL is given. To further demonstrate the effectiveness of the proposed method, two simulated cognitive decision-making tasks are designed, in which pattern representation and decision-making must be jointly developed to achieve good cognitive performance. Our experimental results clearly demonstrate that the resulting learning process is rational and effective. Finally, we indicate that the proposed EEL could be readily further extended by introducing existing machine learning techniques to solve more practical applications.