Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological effects of extracellular fibrinogen binding protein (Efb) in staphylococcus aureus infection

Staphylococcus aureus is a leading cause of human and animal infection. The increasing incidence of antibiotic resistance among strains has complicated treatment of these infections. In order to develop new treatment strategies, it is important to identify and characterise bacterial factors that contribute to infection. S. aureus produces a diverse array of virulence factors, among these Extracellular fibrinogen binding protein, Efb. Efb is one of several fibrinogen-binding proteins produced by S. aureus. Efb is produced in vivo during infection and contributes to the pathogenesis of severe S. aureus wound infection in an animal model. This thesis has been focussed on characterising the biological function of Efb in S. aureus infection. We have shown that Efb interacts with the Aα chain of fibrinogen, at a site of functional importance for the interaction between fibrinogen and platelets. We have studied the effect of Efb on platelet function in vitro and in vivo. Efb bound specifically to a receptor on activated platelets, however fibrinogen was not involved in mediating this binding. Efb stimulated a novel type of fibrinogen binding to the platelet, which did not involve the normal platelet fibrinogen receptor, GPIIb/IIIa. We propose that fibrinogen can also bind to the platelet via Efb and this generates the novel fibrinogen binding mediated by Efb. In the presence of Efb, platelet activation was diminished and Efb also inhibited platelet aggregation in response to various platelet agonists. This antiplatelet effect of Efb was confirmed in vivo. Intravenous Efb significantly prolonged bleeding time but had no effect on the coagulation system. This confirms that Efb specifically inhibits platelet function. Moreover, in a mouse model, intravenous Efb rescued 100% of animals from death due to acute thrombosis. This reflects the inability of the platelets to aggregate in the presence of Efb, an effect so powerful that Efb can counteract the massive thrombosis generated in this model. We have also studied the immune response against Efb and characterised a protective antibody response. Hyperimmune IgG against Efb neutralised Efb and blocked the various biological effects of Efb in vitro. IgG against Efb blocked Efb binding to fibrinogen, neutralised Efb and returned platelet aggregation in the presence of Efb to normal. Furthermore, immunization with Efb protected against the development of severe infection in an animal model of S. aureus infection. The animals in the vaccinated group developed high titre, specific antibodies against Efb and had significantly less severe infection than those in the unvaccinated group. This establishes Efb as a worthy vaccine candidate for S. aureus infection. Collectively, in this thesis we have elucidated the biological function of Efb and confirmed its importance in S. aureus wound infection. Efb is a powerful antiplatelet agent, which impairs haemostasis and wound healing. Efb also represents a worthwhile vaccine candidate for certain S. aureus infections.
Flexural strength of fluorapatite-leucite and fluorapatite porcelains exposed to erosive agents in cyclic immersion

Objective The aim of this study was to evaluate the flexural strength of two porcelain materials (IPS d.SIGN and IPS e.max Ceram) exposed to erosive agents Material and Methods One hundred and twenty bar-shaped specimens were made from each of fluorapatite-leucite porcelain (IPS d.SIGN) and fluorapatite porcelain (IPS e.max Ceram) and divided into 8 groups of 15 specimens each. Six groups were alternately immersed in the following storage agents for 30 min: deionized water (control), citrate buffer solution, pineapple juice, green mango juice, cola soft drink and 4% acetic acid. Then, they were immersed for 5 min in deionized water at 37°C. Seven cycles were completed, totalizing 245 min. A 7th group was continuously immersed in 4% acetic acid at 80°C for 16 h. The final, 8th, group was stored dry at 37°C for 245 min. Three-point bending tests were performed in a universal testing machine. The data were analyzed statistically by 2-way ANOVA, Tukey’s HSD test and t-test at significance level of 0.05. Results The flexural strengths of all groups of each porcelain after exposure to erosive agents in cyclic immersion did not differ significantly (p>0.05). For both types of porcelain, dry storage at 37°C yielded the highest flexural strength, though without significant difference from the other groups (p>0.05). The flexural strengths of all groups of fluorapatite porcelains were significantly higher (p<0.05) than those of the fluorapatite-leucite porcelains. Conclusions This study demonstrated that the erosive agents evaluated did not affect the flexural strength of the tested dental porcelains.
Improved Berezin-Li-Yau inequalities with a remainder term

We give an improvement of sharp Berezin type bounds on the Riesz means $\sum_k(\Lambda-\lambda_k)_+^\sigma$ of the eigenvalues $\lambda_k$ of the Dirichlet Laplacian in a domain if $\sigma\geq 3/2$. It contains a correction term of the order of the standard second term in the Weyl asymptotics. The result is based on an application of sharp Lieb-Thirring inequalities with operator valued potential to spectral estimates of the Dirichlet Laplacian in domains.
Antitumor Activity of Triolimus: A Novel Multidrug-Loaded Micelle Containing Paclitaxel, Rapamycin, and 17-AAG

Triolimus is a first-in-class, multidrug-loaded micelle containing paclitaxel, rapamycin, and 17-AAG. In this study, we examine the antitumor mechanisms of action, efficacy, and toxicity of Triolimus in vitro and in vivo. In vitro cytotoxicity testing of Triolimus was conducted using two aggressive adenocarcinomas including the lung cancer cell line, A549, and breast cancer cell line, MDA-MB-231. The three-drug combination of paclitaxel, rapamycin, and 17-AAG displayed potent cytotoxic synergy in both A549 and MDA-MB-231 cell lines. Mechanistically, the drug combination inhibited both the Ras/Raf/mitogen-activated protein kinase and PI3K/Akt/mTOR pathways. Triolimus was advanced into tumor xenograft models for assessment of efficacy, toxicity, and mechanisms of action. In vivo, a three-infusion schedule of Triolimus inhibited A549 and MDA-MB-231 tumor growth far more potently than paclitaxel-containing micelles and effected tumor cures in MDA-MB-231 tumor-bearing animals. Tumor growth delays resulted from a doubling in tumor cell apoptosis and a 50% reduction in tumor cell proliferation compared with paclitaxel-containing micelles. Enhanced antitumor efficacy was achieved without clinically significant increases in acute toxicity. Thus, Triolimus displays potent synergistic activity in vitro and antitumor activity in vivo with comparable toxicity to paclitaxel. These observations provide strong support for further development of Triolimus and an important proof of concept for safe, effective nanoparticle-based delivery of three complementary anticancer agents. Mol Cancer Ther; 11(10); 2233–42. ©2012 AACR.
Evidence of chaos in the rainfall-runoff process

Abstract The transformation of rainfall into runoff is one of the most important processes in hydrology. In the past few decades, a wide variety of automated or computer-based approaches have been applied to model this process. However, many such approaches have an important limitation in that they treat the rainfall-runoff process as a realization of only a few parameters of linear relationships rather than the process as a whole. What is required, therefore, is an approach that can capture not only the overall appearance but also the intricate details of the nonlinear behaviour of the process. The purpose of this study is to investigate the possibility of understanding the dynamics of the rainfall-runoff process from a new perspective, as a chaotic process. The possible existence of chaotic behaviour in the rainfall-runoff process is studied by investigating the rainfall and runoff time series: (a) separately; and (b) jointly (using the runoff coefficient). Monthly rainfall and runoff observed over a period of 131 years (January 1807-December 1937) at the Göta River basin in the south of Sweden are analysed. The correlation dimension method is employed to identify the presence of chaos. The correlation dimensions obtained for the rainfall and runoff time series are 6.4 and 5.5, respectively. The finite dimensions obtained for the rainfall and runoff time series indicate the possible existence of chaos in these processes, implying that the joint rainfall-runoff process might also exhibit chaotic behaviour. The correlation dimension of about 7.8 obtained for the runoff coefficient also indicates the possible presence of chaos and supports the above results.
Recurrent Hypoglycemic Seizures and Obesity: Delayed Diagnosis of an Insulinoma in a 15 Year-old Boy - Final Diagnostic Localization with Endosonography

Insulinoma in children and adolescents is extremely rare. In adults diagnosis is frequently delayed due to frequent neuropsychiatric symptoms that are misunderstood. Diagnostic localization is sometimes extremely difficult. We present a case of insulinoma with onset of symptoms at the age of 12.5 years. Diagnosis was made very soon after the first symptoms, but diagnostic localization was delayed, since conventional MRI did not reveal the insulinoma. The patient suffered from recurrent hypoglycemic seizures and gained 54 kg in weight until diagnostic localization was made with abdominal MRI, octreotate-PET and finally successful endosonography. A solitary insulinoma in the pancreatic tail was enucleated laparoscopically.
Neuronal Chloride Regulation via KCC2 Is Modulated through a GABAB Receptor Protein Complex

GABAB receptors are G-protein-coupled receptors that mediate inhibitory synaptic actions through a series of downstream target proteins. It is increasingly appreciated that the GABAB receptor forms part of larger signaling complexes, which enable the receptor to mediate multiple different effects within neurons. Here we report that GABAB receptors can physically associate with the potassium-chloride cotransporter protein, KCC2, which sets the driving force for the chloride-permeable ionotropic GABAA receptor in mature neurons. Using biochemical, molecular, and functional studies in rodent hippocampus, we show that activation of GABAB receptors results in a decrease in KCC2 function, which is associated with a reduction in the protein at the cell surface. These findings reveal a novel “crosstalk” between the GABA receptor systems, which can be recruited under conditions of high GABA release and which could be important for the regulation of inhibitory synaptic transmission. SIGNIFICANCE STATEMENT Synaptic inhibition in the brain is mediated by ionotropic GABAA receptors (GABAARs) and metabotropic GABAB receptors (GABABRs). To fully appreciate the function and regulation of these neurotransmitter receptors, we must understand their interactions with other proteins. We describe a novel association between the GABABR and the potassium-chloride cotransporter protein, KCC2. This association is significant because KCC2 sets the intracellular chloride concentration found in mature neurons and thereby establishes the driving force for the chloride-permeable GABAAR. We demonstrate that GABABR activation can regulate KCC2 at the cell surface in a manner that alters intracellular chloride and the reversal potential for the GABAAR. Our data therefore support an additional mechanism by which GABABRs are able to modulate fast synaptic inhibition.
Youth Exercise Intention and Past Exercise Behavior

The study purposes were to examine: (a) the determinants of exercise intention and past exercise behavior (PEB) using the theories of reasoned action and planned behavior, and (b) the moderating influences of sex and exercise group (meeting or not meeting exercise guidelines). Participants (n = 676 adolescents) completed self-reported measures of their exercise attitude, subjective norm, perceived behavioral control (PBC), intention, and PEB. We found that attitude, subjective norm, and PBC explained 55% of the variance in intention, and intention and PBC explained 51% of the variance in PEB. While we found sex and exercise group differences across the study measures, we did not find evidence of significant moderation. Thus, the theory constructs predicted intention and PEB similarly across sex and exercise groups.
Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020?

Background Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980's, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006. Methodology/Principal Findings Two stage random sampling survey in 61 randomly selected Enumeration Areas (EAs) in North Bank Region (NBR) and Lower River Region (LRR). Fifty randomly selected children aged under 10 years were examined per EA for clinical signs of trachoma. In LRR, swabs were taken to test for ocular C. trachomatis infection. Unadjusted prevalences of active trachoma were calculated, as would be done in a trachoma control programme. The prevalence of trachomatous inflammation, follicular (TF) in the 2777 children aged 1–9 years was 12.3% (95% CI 8.8%–17.0%) in LRR and 10.0% (95% CI 7.7%–13.0%) in NBR, with significant variation within divisions (p<0.01), and a design effect of 3.474. Infection with C. trachomatis was found in only 0.3% (3/940) of children in LRR. Conclusions/Significance This study shows a large discrepancy between the prevalence of trachoma clinical signs and ocular C. trachomatis infection in two Gambian regions. Assessment of trachoma based on clinical signs alone may lead to unnecessary treatment, since the prevalence of active trachoma remains high but C. trachomatis infection has all but disappeared. Assuming that repeated infection is required for progression to blinding sequelae, blinding trachoma is on course for elimination by 2020 in The Gambia.
What Noseleaves Do for FM Bats Depends on Their Degree of Sensorial Specialization

Background Many bats vocalizing through their nose carry a prominent noseleaf that is involved in shaping the emission beam of these animals. To our knowledge, the exact role of these appendages has not been thoroughly investigated as for no single species both the hearing and the emission spatial sensitivities have been obtained. In this paper, we set out to evaluate the complete spatial sensitivity of two species of New World leaf-nosed bats: Micronycteris microtis and Phyllostomus discolor. From an ecological point of view, these species are interesting as they belong to the same family (Phyllostomidae) and their noseleaves are morphologically similar. They differ vastly in the niche they occupy. Comparing these species allows us to relate differences in function of the noseleaf to the ecological background of bat species. Methodology/Principal Findings We simulate the spatial sensitivity of both the hearing and the emission subsystems of two species, M. microtis and P. discolor. This technique allows us to evaluate the respective roles played by the noseleaf in the echolocation system of these species. We find that the noseleaf of M. microtis focuses the radiated energy better and yields better control over the emission beam. Conclusions From the evidence presented we conclude that the noseleaves serve quantitatively different functions for different bats. The main function of the noseleaf is to serve as an energy focusing mechanism that increases the difference between the reflected energy from objects in the focal area and objects in the periphery. However, despite the gross morphological similarities between the noseleaves of the two Phyllostomid species they focus the energy to a different extent, a capability that can be linked to the different ecological niches occupied by the two species.
Incorporating Uncertainty into Probabilistic Performance Models of Concentrating Solar Power Plants

A method for applying probabilistic models to concentrating solar-thermal power plants is described in this paper. The benefits of using probabilistic models include quantification of uncertainties inherent in the system and characterization of their impact on system performance and economics. Sensitivity studies using stepwise regression analysis can identify and rank the most important parameters and processes as a means to prioritize future research and activities. The probabilistic method begins with the identification of uncertain variables and the assignment of appropriate distributions for those variables. Those parameters are then sampled using a stratified method (Latin hypercube sampling) to ensure complete and representative sampling from each distribution. Models of performance, reliability, and cost are then simulated multiple times using the sampled set of parameters. The results yield a cumulative distribution function that can be used to quantify the probability of exceeding (or being less than) a particular value. Two examples, a simple cost model and a more detailed performance model of a hypothetical 100-MW e power tower, are provided to illustrate the methods.
Tumour promotion versus tumour suppression in chronic hepatic iron overload

Although iron‐catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague–Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β‐catenin, CHOP, C/EBPα and Yes‐associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β‐catenin levels compared with control livers. Countering these factors, the iron‐loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes‐associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour‐promoting mechanisms in rodent liver. Copyright © 2015 John Wiley & Sons, Ltd.
Admission troponin T, advanced age and male gender identify patients with improved myocardial tissue perfusion after abciximab administration for ST-segment elevation myocardial infarction

Summary The aim was to investigate the effect of abciximab on microvascular perfusion in different subgroups of patients undergoing direct PCI for acute STEMI. We enrolled 145 consecutive patients with TIMI grade 3 flow after direct PCI for acute STEMI. The GPIIb/IIIa inhibitor abciximab was administered in 57 patients (39.3%). Myocardial perfusion was the primary outcome measure and was assessed by analysis of cardiac troponin T wash-out. Treatment effects on myocardial perfusion and clinical outcome were tested for predefined subgroups including patients with an admission cTnT > 0.1µg/L, diabetes mellitus, male gender, age > 70 years, and time from symptom onset to reperfusion > 6 hours. A significant improvement of cTnT washout was seen in patients with an admission cTnT ≥ 0.1 µg/L, in males and in older patients. Improved tissue level reperfusion did not translate into a significant reduction of cardiac mortality or the incidence of the combined endpoint consisting of cardiac death, nonfatal reinfarction and need for target vessel revascularisation during 30 dayand long-term follow-up (mean 274 days). In conclusion, adjunctive administration of abciximab improves myocardial perfusion in patients with normal epicardial flow after direct PCI, particularly in patients with an cTnT > 0.1µg/L on admission, age over 70 years and male gender.
RYR2 Proteins Contribute to the Formation of Ca2+ Sparks in Smooth Muscle

Calcium release through ryanodine receptors (RYR) activates calcium-dependent membrane conductances and plays an important role in excitation-contraction coupling in smooth muscle. The specific RYR isoforms associated with this release in smooth muscle, and the role of RYR-associated proteins such as FK506 binding proteins (FKBPs), has not been clearly established, however. FKBP12.6 proteins interact with RYR2 Ca2+ release channels and the absence of these proteins predictably alters the amplitude and kinetics of RYR2 unitary Ca2+ release events (Ca2+ sparks). To evaluate the role of specific RYR2 and FBKP12.6 proteins in Ca2+ release processes in smooth muscle, we compared spontaneous transient outward currents (STOCs), Ca2+ sparks, Ca2+-induced Ca2+ release, and Ca2+ waves in smooth muscle cells freshly isolated from wild-type, FKBP12.6−/−, and RYR3−/− mouse bladders. Consistent with a role of FKBP12.6 and RYR2 proteins in spontaneous Ca2+ sparks, we show that the frequency, amplitude, and kinetics of spontaneous, transient outward currents (STOCs) and spontaneous Ca2+ sparks are altered in FKBP12.6 deficient myocytes relative to wild-type and RYR3 null cells, which were not significantly different from each other. Ca2+ -induced Ca2+ release was similarly augmented in FKBP12.6−/−, but not in RYR3 null cells relative to wild-type. Finally, Ca2+ wave speed evoked by CICR was not different in RYR3 cells relative to control, indicating that these proteins are not necessary for normal Ca2+ wave propagation. The effect of FKBP12.6 deletion on the frequency, amplitude, and kinetics of spontaneous and evoked Ca2+ sparks in smooth muscle, and the finding of normal Ca2+ sparks and CICR in RYR3 null mice, indicate that Ca2+ release through RYR2 molecules contributes to the formation of spontaneous and evoked Ca2+ sparks, and associated STOCs, in smooth muscle.