Miracle-dz/UniFAR-FTUs huggingface dataset:
Newly Synthesized Rho A, Not Ras, Is Isoprenylated and Translocated to Membranes Coincident with Progression of the G1 to S Phase of Growth-stimulated Rat FRTL-5 Cells*

Ras and Rho are involved in the regulation of signal transduction events governing cell growth and cell proliferation. Protein prenylation is essential for the activation and/or the translocation of these small GTPases; however, protein geranylgeranylation rather than farnesylation is required for G1/S transition. We studied prenylation and translocation of Ras and Rho A during G1/S progression in growth-stimulated rat thyroid FRTL-5 cells. Immunoblot analysis revealed that both Ras and Rho A were detected in membrane fractions at G0. Rho A was eliminated from the membrane fraction during G1 and was not detected on the membrane at mid-G1. Translocation of Rho A from the cytoplasm back to the membranes was observed during late G1 phase. In contrast, Ras remains in the membrane fraction through the cell cycle progression from G1 to S phase. The immunoprecipitation of Rho A from the membrane fraction demonstrated that newly synthesized Rho A, labeled by pulsing cells with [35S]methionine and [35S]cysteine, was geranylgeranylated and associated with the membrane in late G1. These results indicate that Rho A, not Ras, was eliminated from membrane fraction during G1 progression and that newly synthesized Rho A is geranylgeranylated and translocated to membranes during G1/S progression in growth-stimulated FRTL-5 cells.
Lack of Interactions between Breast Cancer Resistance Protein (BCRP/ABCG2) and Selected Antiepileptic Agents

Summary: Purpose: Recent studies have indicated constitutive expression of efflux transporter, breast cancer resistance protein (BCRP, ABCG2), in endothelial cells of the blood–brain barrier (BBB). In epileptogenic brain tumors such as ganglioma, astrocytoma, anaplastic astrocytomas, or glioma multiforme, strong expression of BCRP in the microvasculature of the BBB was observed. Therefore it was hypothesized that this phenomenon could critically influence the bioavailability of drugs in these tumors and potentially contribute to the failure of antiepileptic treatment. The aim of this study was to test whether some commonly used antiepileptic drugs (AEDs) are substrates transported by human BCRP. In particular, we focused on phenobarbital, phenytoin, ethosuximide, primidone, valproate, carbamazepine, clonazepam, and lamotrigine. Furthermore, the inhibitory potency of these AEDs to BCRP was examined.
Assessment of new therapies for infection due to the Mycobacterium avium complex: appropriate use of in vitro and in vivo testing.

Laboratory testing is a prerequisite to predictions about the potential value of human clinical trials--the gold standard for the assessment of new therapies for infection with the Mycobacterium avium complex (MAC). These laboratory assessments must be made in the proper sequence, with appropriate models and methodology used to obtain data valid in determining whether clinical trials are warranted. In vitro testing permits measurements of minimal inhibitory and minimal bactericidal concentrations, identification of the synergism or antagonism of various agents, definition of an agent's pharmacokinetic properties (e.g., hydrophilicity or lipophilicity), and evaluation of a drug's intracellular penetration and activity against intracellular organisms. The most appropriate animal model for in vivo testing of activity against MAC is the beige mouse. Experiments in this model provide important data on an agent's minimal effective dose and on its optimal dose, dosing frequency, and route(s) of administration. Evaluations in the beige mouse also document whether the agent is bactericidal or bacteriostatic, whether it selects drug-resistant mutants, and whether its use in combination with other agents is beneficial.
Pattern of coronary artery disease with no risk factors under age 35 years.

BACKGROUND Coronary artery disease (CAD) is no more deemed to be an ailment of the 4th or 5th decade; rather an earlier age incidence is not infrequently encountered in our population. However, there are a few data regarding CAD in young adults, and much about its underlying pathology still remains undetermined. The objective of this study was to delineate the coronary arterial disease pattern in adults under the age of 35 years, but having no known coronary risk factors. METHODS This prospective study was conducted at the Cardiology Departments of all 3 public sector tertiary care hospitals in Peshawar from Jun 2008 to Dec 2009. After having excluded the traditional risk factors for CAD, patients under the age of 35 years with objective evidence of CAD were subjected to percutaneous coronary angiography. RESULTS Out of a total of 104 patients, 85 (81.73%) patients were men, and 19 (18.27%) were women. The mean age of the whole group was 32.66 +/- 3.237 (22-35) years. Significant CAD (> 50% diameter narrowing of at least one major coronary artery) was found in 87 (83.7%) patients while 17 (16.3%) patients had non-atherosclerotic coronary artery disease, including 12 (11.53%) patients having normal coronary arteries, 1 (1%) patient had anomalous origin of right coronary artery (RCA), 1 (1%) patient had coronary arteritis, 2 (1.92%) patients had coronary artery ectasia, and 1 (1%) patient had a myocardial bridge over left anterior descending artery (LAD). Among the patients with significant CAD, the prevalence rate of one, two and three vessel disease was 54 (51.9%), 22 (21.2%) and 11 (10.6%) respectively. Almost 50% of the lesions occurred in LAD followed by 25% in RCA and 20% in circumflex, while only one patient (1%) had isolated significant CAD of left main coronary artery. Osteal segments were involved in 10%, proximal in 61%, mid in 21% and distal segments in 7% of the lesions. CONCLUSION In the younger age group, CAD is mostly a disease of men, single vessel CAD predominates with LAD involvement mostly, predominant osteal to proximal segment involvement of vessels, and a much higher incidence of normal coronaries and non-obstructive CAD is met with.
Computed Tomographic Colonography (Virtual Colonoscopy): A New Method for Detecting Colorectal Neoplasms

Computed tomographic (CT) colonography is an exciting new technique that uses volumetric CT data combined with advanced imaging software to create two-dimensional and three-dimensional images of the colon. The technique uses both three-dimensional images that simulate the endoluminal perspective of the colonoscope, as well as axial and reformatted two-dimensional images. The two-dimensional and three-dimensional images are complementary, and in combination offer the most robust performance for the detection of colorectal polyps. Currently, CT colonographic examinations are performed in the fully cleansed and air-inflated colon using a slice thickness of 5 mm, a reconstruction interval of 3 mm, a pitch of 1.3, and 70 mA. In a blinded, prospective study of 70 patients (half with a known lesion, and half from a surveillance population with a low disease prevalence) the sensitivity for the detection of polyps of 1 cm or more is 75%, and the specificity is 90%. The most commonly encountered problems include retained colonic fluid and stool, suboptimally distended colonic segments, and long interpretation times. Many of these problems can be solved using both supine and prone imaging. It is expected that the performance of this examination will improve, and that a new era of colorectal screening will begin.
International capital flows in club of convergence

PurposeThe paper analyzes the pattern of international capital flows, accounting for the convergence on economic growth.Design/methodology/approachThe paper employs an empirical analysis combined with a theoretical model. The evidence is based on a cross-section regression over a sample of 172 economies. And the model is an open multi-country overlapping generation (OLG) economy.FindingsThe empirical evidence records that the pattern of international capital flows in the club of convergence can diverge from the pattern in the club of unconvergence. A higher productivity growth rate is associated with more net capital inflows in the club of convergence but less net capital inflows in the club of unconvergence. The theory shows that proximity to world technology frontier can explain the divergence of capital flows.Research limitations/implicationsThe result can account for controversies between theories on the cross-border capital flows: allocation puzzle, up-hill capital flows and neoclassical growth model.Originality/valueThe paper combines both the empirical analysis with the theoretical model construction to account for the role of convergence of economic growth on determining the pattern of international capital flows.
Epidemiology of invasive pneumococcal infections in infants and young children in Metropolitan Santiago, Chile, a newly industrializing country.

AIM To study the epidemiology of invasive pneumococcal infections in infants and young children in Santiago, Chile, as a representative pediatric population in a newly industrializing country where pneumococcal conjugate vaccines may be used in the future. METHODS A 5-year retrospective laboratory-based review (1989 to 1993) was followed by a 3-year prospective laboratory and hospital surveillance study in two of the six health administrative areas of Santiago to detect all hospitalized cases of invasive pneumococcal disease (defined as Streptococcus pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile site) among infants and children (0 to 23 months of age in the retrospective and 0 to 59 months of age in the prospective study). RESULTS During the 5-year retrospective survey the incidence of invasive pneumococcal disease was 90.6 cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12 to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5) toddlers) were recorded during the 3 years of prospective surveillance. Among the 110 cases in children 0 to 59 months of age detected during the 3-year prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were antigenic types that would be covered by the 11- or 9-valent conjugate vaccines under development. CONCLUSIONS Invasive pneumococcal infections in Santiago, Chile, exhibit an epidemiologic pattern intermediate between that of developing and industrialized countries. The high burden of disease in early infancy dictates that an accelerated immunization schedule (beginning in the perinatal period) or maternal immunization with pneumococcal vaccines should be explored.
Integration of BpMADS4 on various linkage groups improves the utilization of the rapid cycle breeding system in apple.

Rapid cycle breeding in apple is a new approach for the rapid introgression of agronomically relevant traits (e.g. disease resistances) from wild apple species into domestic apple cultivars (Malus × domestica Borkh.). This technique drastically shortens the long-lasting juvenile phase of apple. The utilization of early-flowering apple lines overexpressing the BpMADS4 gene of the European silver birch (Betula pendula Roth.) in hybridization resulted in one breeding cycle per year. Aiming for the selection of non-transgenic null segregants at the end of the breeding process, the flower-inducing transgene and the gene of interest (e.g. resistance gene) that will be introgressed by hybridization need to be located on different chromosomes. To improve the flexibility of the existing approach in apple, this study was focused on the development and characterization of eleven additional BpMADS4 overexpressing lines of four different apple cultivars. In nine lines, the flowering gene was mapped to different linkage groups. The differences in introgressed T-DNA sequences and plant genome deletions post-transformation highlighted the unique molecular character of each line. However, transgenic lines demonstrated no significant differences in flower organ development and pollen functionality compared with non-transgenic plants. Hybridization studies using pollen from the fire blight-resistant wild species accession Malus fusca MAL0045 and the apple scab-resistant cultivar 'Regia' indicated that BpMADS4 introgression had no significant effect on the breeding value of each transgenic line.
Modelling and Forecasting Stock Returns Volatility on Uganda Securities Exchange Using Univariate Garch Models

Stock returns volatility of daily closing prices of the Uganda Securities Exchange (USE) all share index over a period of 04/01/2005 to 18/12/2013 is Modelled. We employ different univariate Generalised Autoregressive Conditional Heteroscedastic(GARCH) models; both symmetric and asymmetric. The models include; GARCH(1,1), GARCH-M, EGARCH(1,1) and TGARCH(1,1). Quasi Maximum Likelihood(QML) method was used to estimate the models and then the best performing model obtained using two model selection criteria; Akaike Information criterion(AIC) and Bayesian Information criterion(BIC). Their forecasting abilities was determined using two loss functions; Mean square error (MSE) and Mean absolute error (MAE). The GARCH(1, 1) model outperformed the other competing models in modelling volatility while EGARCH(1, 1 )performed best in forecasting volatility of USE returns.
Mechanisms of Action of Probiotics in Intestinal Diseases

Intestinal microbiota is a positive health asset that exerts a conditioning effect on intestinal homeostasis. Resident bacteria deliver regulatory signals to the epithelium and instruct mucosal immune responses. Recent research has revealed a potential therapeutic role for the manipulation of the microbiota and exploitation of host-microbial signalling pathways in the maintenance of human health and treatment of various mucosal disorders. A variety of pharmabiotic strategies, such as the use of specific members of the microbiota, their surface components, or metabolites, as well as genetically modified commensal bacteria, are being investigated for their ability to enhance the beneficial components of the microbiota. It is clear that engagement with host cells is central to pharmabiotic action, and several strain-specific mechanisms of action have been elucidated. However, the molecular details underpinning these mechanisms remain almost entirely unknown. Understanding how pharmabiotics exert their beneficial effects is critical for the establishment of definitive selection criteria for certain pharmabiotic strategies for specific clinical conditions. Scientifically accredited evidence of efficacy and studies to elucidate the molecular mechanisms of host-microbiota interactions are needed to lend credence to the use of pharmabiotic strategies in clinical medicine.
Analysis of Intracochlear New Bone and Fibrous Tissue Formation in Human Subjects with Cochlear Implants

Objectives: In this study we aimed to evaluate new bone and new fibrous tissue formation in the inner ear following cochlear implantation. Methods: Twelve temporal bones from patients who underwent cochlear implantation during life were prepared for histologic study. The specimens were reconstructed by both 2-dimensional and 3-dimensional methods. These reconstructions were used to calculate the total volume and distribution of new bone and new fibrous tissue in the cochlea, the number of spiral ganglion cells, and other histopathologic parameters. Clinical data, including the last-recorded word recognition scores, were obtained from the patients' medical records. Results: New bone and new fibrous tissue were found in all 12 specimens, particularly at the site of cochleostomy. There was a significant correlation between overall damage to the lateral cochlear wall and the total volume of intracochlear new tissue (Spearman rho = .853; p = .0004). The total volume of new tissue did not correlate with word recognition scores or spiral ganglion cell counts. Conclusions: These preliminary results suggest that the degree of damage to the lateral cochlear wall may play an important role in influencing the amount of new tissue formation following cochlear implantation. Intracochlear new tissue does not appear to be an important determinant of performance as measured by word recognition scores or the total number of remaining spiral ganglion cells.
Tone discrimination in Cantonese-speaking children using a cochlear implant

Most tone perception tests for Cantonese-speaking cochlear implant users have been based on tone identification tasks which require significant cognitive development to be successfully completed. Results from such tests suggest that cochlear implant child users are performing at about chance level and may not be receiving much information about pitch using the implant. This paper reports on the ability of cochlear implant child users to discriminate pitch variations in Cantonese by using an experimental procedure based on play audiometry. As part of the study, the usefulness of higher rates of electrode stimulation for aiding tone discrimination is also examined. Cochlear implant users are shown to derive sufficient information about pitch to discriminate most tone contrasts relatively successfully, with performance being most variable for contrasts involving tones clustered in the lower register of the speaker's fundamental frequency range. Contrary to hypothesis, higher electrode stimulation rates are not found to offer significant benefits for aiding pitch discrimination.
Prior antimicrobial use as a risk factor for resistance in selected Staphylococcus pseudintermedius isolates from the skin and ears of dogs.

BACKGROUND Antimicrobial resistance within bacteria continues to present therapeutic challenges. One presumed risk factor for increased rates of resistance is prior exposure to antimicrobial drugs. OBJECTIVES To examine the impact of time since most recent exposure, the number of prior antimicrobial exposures and duration of use on antimicrobial resistance rates in Staphylococcus pseudintermedius isolates. METHODS Inclusion of a case in the study required laboratory isolation of S. pseudintermedius from a clinical specimen. Antibiograms and information regarding prior antimicrobial exposures were extracted from the medical records of dogs diagnosed with pyoderma or otitis externa. RESULTS Meticillin resistance (MR) was identified in 48.1% of isolates. Recent use of beta-lactam antimicrobials was associated with increased odds of resistance to meticillin (P < 0.001) and fluoroquinolones (P < 0.001). Antimicrobial therapy within 1 month prior to sampling was also associated with MR (60.7%; P = 0.009) and multidrug resistance (61.9%; P = 0.029). The number of prior exposures to beta-lactams or fluoroquinolones were associated with resistance to these same classes (P = 0.001 and 0.02, respectively) and to other antimicrobial classes (P = 0.016 for resistance to fluoroquinolones following treatment with beta-lactams and P = 0.015 for MR following treatment with fluoroquinolones). Longer treatment duration with beta-lactam drugs was associated with higher proportion of MR (P = 0.004). CONCLUSIONS AND CLINICAL IMPORTANCE Treatment based upon culture and susceptibility testing is highly recommended for dogs that have received multiple antimicrobial drug exposures or that were treated within the preceding month. This may be especially important when the prior therapeutic regimen included a drug from the beta-lactam or fluoroquinolone classes.
Abnormalities of carnitine metabolism in chronic fatigue syndrome

Carnitine may be involved in the pathogenesis of the chronic fatigue syndrome (CFS). However, no information about the cellular metabolism of carnitine in CFS patients is currently available. Therefore, we aimed to measure the levels of carnitine (total, free and short‐chain) in both peripheral blood lymphocytes (PBLs) and sera from patients with CFS. The serum levels of total, free and short‐chain were comparable in CFS patients, considered as the whole group, to those in healthy control subjects, even though a trend indicating slightly reduced serum concentrations of free carnitine was observed in male patients with CFS. In contrast, the concentrations of total, free and short‐chain carnitine in PBLs from patients with CFS were significantly lower than in cells from healthy controls. Our study indicates that patients with CFS require exogenous carnitine supplementation. The low carnitine concentrations in PBLs from patients with CFS probably reflect the carnitine deficiency occurring in other tissues, including the skeletal muscles. The low cellular concentrations of carnitines may help to explain both the immunological abnormalities and the impaired energy metabolism in skeletal muscles.
The clinical safety of ibrutinib in chronic lymphocytic leukemia

Introduction: Ibrutinib, a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. Areas covered: Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. Expert opinion: Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited.
Small increases in extravascular lung water are accurately detected by transpulmonary thermodilution.

BACKGROUND Detection of small (10-20%) increases in lung water may be relevant to detect incipient pulmonary edema but no clinically usable method has demonstrated this capability to date. METHODS In six pigs weighing 28 to 35 kg, we performed 18 determinations of extravascular lung water (EVLW; transpulmonary thermodilution method) before and immediately after the intratracheal introduction of 50 mL of saline solution. Six determinations were performed in normal lung and 12 in edematous lung. RESULTS In normal lung, the mean of EVLW increased from 245 +/- 18 mL to 288 +/- 19 mL (p < 0.001) after the intratracheal introduction of 50 mL of saline solution; therefore, 43 of the 50 mL (84%) were detected (range, 37-48 mL). In edematous lung, the EVLW increased from 491 +/- 106 mL to 530 +/- 108 mL after the introduction of 50 mL of saline solution; therefore, 39 of the 50 mL (77%) were detected (range, 15-67 mL). CONCLUSION The transpulmonary thermodilution technique accurately detects small increases in extravascular lung water and may permit accurate diagnosis of incipient pulmonary edema.