Miracle-dz/UniFAR-FTUs huggingface dataset:
Glyburide and tolbutamide induce desensitization of insulin release in rat pancreatic islets by different mechanisms.

Insulin secretion was studied in rat pancreatic islets after 24-h exposure to various glyburide or tolbutamide concentrations. Glucose-induced insulin release was significantly (P < 0.05) reduced in islets cultured with 0.1 microM glyburide or 100 microM tolbutamide (2098 +/- 187, 832 +/- 93, and 989 +/- 88 pg/islet.h in control, glyburide-exposed, and tolbutamide-exposed islets, respectively). When glyburide-treated islets were stimulated with glyburide or tolbutamide, insulin release was also impaired compared to that in control islets (P < 0.05). In contrast, tolbutamide-exposed islets showed an impaired response to tolbutamide, but a normal response to glyburide. To investigate the mechanism of the sulfonylurea-induced impairment of insulin secretion, we measured insulin release and Rb+ efflux (a marker of the K+ channel activity) in a perifusion system and islet Ca2+ uptake under static conditions. Insulin release in response to 16.7 mM glucose increased in control islets from 9.4 +/- 1.1 to 131 +/- 19 pg/islet.min (first phase secretion peak). Simultaneously, the fractional 86Rb+ efflux declined from 0.015 +/- 0.002% to 0.006 +/- 0.001% (change in decrement, -63.5%). Glucose-induced insulin release in glyburide- and tolbutamide-treated islets was significantly reduced (first phase peak, 22.1 +/- 5 and 39.7 +/- 8 pg/islet.min, respectively; P < 0.05), and the fractional 86Rb+ efflux decrement was -21 +/- 6% for glyburide (P < 0.005 vs. control islets) and -65 +/- 4% (not different from control) for tolbutamide. When glyburide- or tolbutamide-exposed islets were stimulated with the corresponding sulfonylurea, insulin release was impaired compared to that in control islets (P < 0.05), but, again, 86Rb+ efflux was impaired (P < 0.05) only in glyburide-exposed islets. When 45Ca2+ uptake was studied, the increase in glucose concentration from 2.8 to 16.7 mM increased calcium uptake in control islets from 1.76 +/- 0.58 to 7.27 +/- 1.36 pmol/islet.2 min (n = 4). Preexposure to 0.1 microM glyburide did not change calcium uptake at a glucose concentration of 2.8 mM (1.44 +/- 0.45 pmol/islet.2 min) but significantly reduced calcium uptake stimulated by 16.7 mM glucose (3.21 +/- 0.35 pmol/islet.2 min; n = 4; P < 0.005 compared to control islets). In contrast, preexposure to 100 microM tolbutamide did not change either basal or glucose-stimulated calcium uptake (1.44 +/- 0.45 and 6.90 +/- 0.81 pmol/islet.2 min, respectively; n = 4). These data show that in vitro chronic exposure of pancreatic islets to the sulfonylureas glyburide and tolbutamide impairs their ability to respond to a subsequent glucose or sulfonylurea stimulation. (ABSTRACT TRUNCATED AT 400 WORDS)
Impedance control of an aerial manipulator

This work focuses on the modeling and control of an innovative configuration of aerial robot arising from the combination of a vertical take-off and landing aircraft and a robotic arm. The overall system, denoted as aerial manipulator, is able to accomplish operations requiring the physical interaction with the surrounding environment while remaining airborne. After introducing a detailed dynamical model, a control law, based on the impedance control paradigm, able to govern all the degrees of freedom of the system is proposed. The effectiveness of the proposed control algorithm are investigated also considering the case in which contacts with the surrounding environment are achieved.
Risk Governance in the Insurance Sector—Determinants and Consequences in an International Sample

We analyze the relation between risk governance, risk, and performance measures for a global sample of 107 insurance companies from 2004 to 2012. Our risk governance index (RGI) covers several Solvency II provisions and includes the existence of chief risk officer on the executive committee, risk committee characteristics, and board industry experience. We find that in the crisis period 2008–2009, firms with a higher RGI generally have lower expected default frequency. We conclude that during noncrisis years, risk governance does not have a risk-reducing effect but is positively associated with buy-and-hold returns, risk-adjusted performance measures, and Tobin's Q. Our findings therefore support the role of risk governance as a business enabler rather than inhibitor. Insurance companies typically upgrade their risk governance following a negative shock, especially in countries that are well regulated and have weaker shareholder rights.
The Influence of Granisetron on the Pharmacokinetics and Pharmacodynamics of Docetaxel in Asian Lung Cancer Patients

BACKGROUNDDocetaxel, which undergoes hepatic metabolism via cytochrome P450 3A4, is a promising anticancer agent. Toxicity is serious problem, however, because it is difficult to predict the cytochrome P450 3A4 activity of the drug. Moreover, drug-drug interactions involving cytochrome P450 3A4 enzymes are important. Granisetron, a selective antagonist of the 5-hydroxytryptamine3 receptor, also undergoes hepatic metabolism via cytochrome P450 3A4. In this study, we investigated the influence of granisetron on the pharmacokinetics and pharmacodynamics of docetaxel in Asian patients with lung cancer. METHODSSix patients with advanced lung cancer were treated with doses of docetaxel (60 mg/m2). In the first course of treatment, no antiemetic agents were administered. In the second course, all patients received 3.0 mg of granisetron before 30-minute administration of docetaxel. In each of the treatment courses, blood samples (5 mL) were obtained for pharmacokinetic study at the following times: 0, 0.5, 1.5, 2.0, 3.0, 5.0, 8.0, and 24 hours after the start of the docetaxel infusion. RESULTSSix patients were enrolled in this pharmacokinetics study. The mean ± SD systemic clearance of docetaxel administered alone or in combination with granisetron was 32.9 ± 8.3 and 28.2 ± 5.9, respectively. The area under the concentration-versus-time curve of plasma docetaxel (alone or in combination with granisetron) ranged from 1.355 to 2.773 and 1.647 to 3.079 μg × h/mL (mean ± SD: 1.936 ± 0.541 and 2.219 ± 0.510 μg × h/mL), respectively. There was no significant difference in mean residence time (or invariance of residence time) between the single dose of docetaxel and the combination of docetaxel and granisetron. DISCUSSIONWe found no significant difference in the pharmacokinetic and pharmacodynamic parameters of docetaxel between the single dose of docetaxel and the combination of docetaxel and granisetron. However, a wide interindividual variation existed in cytochrome P450 3A4 activity. It is clear that the results of the present study should be confirmed in a population study involving a larger number of subjects addressing the genetic variations of drug metabolizing enzymes, drug receptors, and drug transporters.
Physical Mechanism of Interfacial Thermal Resistance in Electronic Packaging Based on a Mixed MD/FE Model

A multiscale model is constructed to study interfacial thermal resistance in electronic packaging. The model combines a molecular dynamics simulation for the critical regions within the system with a finite element (FE) method for a continuum description of the remainder of the system. For nonequilibrium simulations, the establishment of the proper boundary condition is very difficult. In this mixed model, the continuum subdomain serves primarily as a boundary model that provides the low frequency impedance and a sink for the energy associated with outgoing waves of the molecular dynamics model. The simulations results show that the temperature distribution is nonuniform along the interface. At primary stage, the interfacial thermal resistance is unstable and will become very large at certain time steps. At the last stage, the change of interfacial thermal resistance tends to be stable. There are few direct experimental measurements of the interfacial thermal resistance between dissimilar materials, while the similar experimental results support the conclusions in this paper.
Adoption of emerging technologies into ERP systems landscape: A South African study

Innovations are continuously pushing the boundaries of how organizations can use various technologies to improve efficiency. However, for organizations making use of large applications such as enterprise systems to support their operations, the process of adopting new technologies can have huge implications. This study focuses on the introduction of cloud computing, mobile technology, in-memory technology, and service oriented architecture into existing enterprise systems for companies operating in a developing country context. The findings reveal that while many organizations are seriously considering these technologies, issues such as lack of sufficient knowledge, skills shortages and concerns on security, costs as well as legislation are still a challenge.
Lack of Torpor in Free-Ranging Southern Lesser Galagos, Galago moholi: Ecological and Physiological Considerations

Studies investigating heterothermy under natural conditions are particularly scarce for tropical species. However, heterothermy patterns in tropical and subtropical environments often differ markedly from those observed in arctic and temperate species. The investigation of heterothermy in strepsirhine primates has focussed largely on the Malagasy cheirogaleids. In addition, a physiological verification of torpor occurrence in mainland strepsirhines is important with regard to arguments pertaining to the colonization of Madagascar by strepsirhine primates. We measured body temperatures of 11 free-ranging Galago moholi, between February 2002 and September 2003, for 3 consecutive months for each animal. No incidents of heterothermy were recorded throughout the study period. We considered how physiological and ecological aspects of G. moholi biology might have obviated the use of torpor. It was suggested that the breeding pattern observed in G. moholi prevented torpor use whilst increasing fecundity, and that the ecological costs of torpor far outweighed the energetic costs. This study highlights the need for more studies on free-ranging animals to elucidate the physiological, ecological and phylogenetic constraints and determinants of torpor use. Furthermore, if convincing arguments are to be made regarding the possible role of heterothermy in species dispersal, more data from free-ranging animals are needed.
Alcohol dehydrogenase I expression correlates with CDR1, CDR2 and FLU1 expression in Candida albicans from patients with vulvovaginal candidiasis

Background The most critical mechanism governing drug resistance in Candida albicans (C. albicans) involves efflux pumps, the functionality of which largely depends on energy metabolism. Alcohol dehydrogenase I (ADH1) plays an important role in intracellular energy metabolism. The aim of this study was to explore the relationship between ADH1 and drug resistance in C. albicans. Methods Twenty clinical C. albicans samples isolated from individual patients diagnosed with vulvovaginal candidiasis, and two C. albicans strains obtained from a single parental source (the fluconazole (FLC)‐sensitive strain CA‐1sand the FLC‐resistant strain CA‐16R) were included in our study. In accordance with the Clinical and Laboratory Standards Institute (CLSI) M27‐A3 guidelines, we used the microdilution method to examine the FLC minimum inhibitory concentrations (MICs) and real‐time reverse transcription polymerase chain reaction (RT‐PCR) to measure the mRNA expression levels of ADH1 and the azole resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in all the isolates. Results A highly significant positive correlation between the mRNA levels of ADH1 and the MICs (rs =0.921, P=0.000), as well as positive correlations between the mRNA level of ADH1 and those of CDR1, CDR2 and FLU1 (rs of 0.704, 0.772 and 0.779, respectively, P <0.01), were observed in the 20 clinical C. albicans samples. The relative expression of ADH1 was upregulated 10.63‐ to 17.61‐fold in all of the drug‐resistant isolates. No correlations were found between the mRNA levels of ADH1 and those of MDR1 or ERG11(P >0.05). The mRNA levels of the examined drug resistance genes were higher in the CA‐16R strain than in CA‐1S, and the mRNA levels of ADH1 in CA‐16R were 11.64‐fold higher than those in CA‐1S(P <0.05). Conclusions These results suggest that high levels of ADH1 transcription are implicated in FLC resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1.
Muscles of a different 'color'

The rules that govern many aspects of skeletal muscle structure and function are very different for the extraocular muscle allotype. The myoblast lineages present in the extraocular muscle primordia are permissive for generation of an unusually wide range of fiber types. The balance that is struck between genetic specification and activity dependent factors in shaping fiber phenotype to suit the demands of complex visuomotor systems is not yet well defined. Because skeletal muscle has high energy demands, diversity in fiber types is needed to maximize efficiency; greater diversity in fiber composition then indicates a more diverse functional repertoire. Together, the characteristics of small motor unit size, precise dependence of muscle force upon motor neuron discharge rate, high contractile speed but low tension development, and contractile protein heterogeneity contribute toward the high precision and diversity that is required for eye movements. Finally, the structural and functional characteristics and plasticity of the individual extraocular muscle fiber types play an important role in determining their response to disease or manipulation. The lack of uniform responses across the muscle allotypes in disease, or in response to pharmaceutical or surgical interventions, requires that we obtain a better understanding of the fundamental differences that exist between muscle groups.
Peripheral T‐cell lymphoma: A clinicopathologic study of 42 cases

We analysed the clinical and pathologic features of 42 patients with immunologically confirmed peripheral T‐cell lymphoma. The median age was 60 years and the male to female ratio was 1:1. A prior lymphoprolifera‐tive or autoimmune disorder was present in 14 per cent of the patients. Signs of advanced disease were usually present from the onset, such as B symptoms (55 per cent), generalized lymphadenopathy (57 per cent), stage III/IV disease (62 per cent), and elevated levels of serum lactate dehydrogenase (68 per cent). Primary extranodal disease (14 per cent), hepatomegaly (12 per cent), splenomegaly (12 per cent), lung/pleural involvement (12 per cent), skin involvement (21 per cent), and bone marrow involvement (28 per cent) were uncommon. Lymphocytopenia was present in 64 per cent of the patients, and none of nine patients tested were serologically positive for human T‐cell leukemia/lymphoma virus (HTLV‐I) infection. Among 38 patients receiving combination chemotherapy, 20 (53 per cent) achieved a complete remission. The actuarial median survival of all patients was 17 months. Age greater than 60 years and stage III/IV disease predicted a poor clinical outcome, whereas the large cell histological subtype predicted a favourable outcome. Prospective clinical studies using uniform treatments and a uniform histologic classification scheme are needed to confirm these findings.
Early Two-Stage Double Opposing Z-Plasty or One-Stage Push-Back Palatoplasty?: Comparisons in Maxillary Development and Speech Outcome at 4 Years of Age

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm′: ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N′-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N′: ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S′: ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2-stage protocol is advantageous with regard to maxillary growth compared with 1-stage push-back palatoplasty without compromising speech development as evaluated for all children at 4 years of age.
Differential expression of p53, p63 and p73 protein and mRNA for DMBA‐induced hamster buccal‐pouch squamous‐cell carcinomas

Abnormalities in the p53 gene are regarded as the most consistent of the genetic abnormalities associated with oral squamous‐cell carcinoma. Two related members of the p53 gene family, p73 and p63, have shown remarkable structural similarity to p53, suggesting possible functional and biological interactions. The purpose of this study was to investigate the differential expression of p73, p63 and p53 genes for DMBA‐induced hamster buccal‐pouch squamous‐cell carcinoma. Immunohistochemical analysis for protein expression and reverse transcriptase‐polymerase chain reaction (RT‐PCR) for mRNA expression were performed for 40 samples of hamster buccal pouches, the total being separated into one experimental group (15‐week DMBA‐treated; 20 animals) and two control groups (untreated and mineral oil‐treated; 10 animals each). Using immunohistochemical techniques, nuclear staining of p53 and p73 proteins was detected in a subset of hamster buccal‐pouch tissue specimens treated with DMBA for a period of 15 weeks, whereas p63 proteins were noted for all of the 20 hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks as well as for all of the untreated and mineral oil‐treated hamster buccal‐pouch tissue specimens. Differential expression of p63, p73 and p53 protein for the experimental group was as follows: p63+/p73+/p53+ (n = 14; 70%); p63+/p73+/p53– (n = 2; 10%); p63+/p73–/p53– (n = 4; 20%) and p63+/p73–/p53– (untreated [n = 10] and mineral oil‐treated mucosa [n = 10]; 100% each). Upon RT‐PCR, ΔNp63mRNA was detected within all of the 20 hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks, whereas expression of TAp63 was not detected. Furthermore, p73 mRNA was identified for 16 of the hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks, whereas p53 mRNA was noted for 14 15‐week DMBA‐treated pouches. The proportional (percentage) expression of ΔNp63, p73 and p53 mRNA for the hamster buccal‐pouch tissue specimens treated with DMBA for 15 weeks was noted to be consistent with the findings using immunohistochemical techniques. A significant correlation between p53, p63 and p73 expression (protein and mRNA) was demonstrated for the hamster buccal‐pouch carcinoma samples. Our results indicate that both p73 and p63 may be involved in the development of chemically induced hamster buccal‐pouch carcinomas, perhaps in concert with p53.
Endothelial NO Synthase Genotype and Risk of Preeclampsia: A Multicenter Case-Control Study

Polymorphisms in the endothelial NO synthase (eNOS) gene have been evaluated as risk factors for preeclampsia. However, data from small studies are conflicting. We assessed whether eNOS genotypes alter the risk of preeclampsia in a population in which the incidence of this disorder is high. A total of 844 young pregnant women (322 preeclamptic and 522 controls) were recruited from 5 cities. Genotyping for the Glu298Asp, intron-4 and –786T→C polymorphisms in the eNOS gene was conducted. Multivariate odds ratios (ORs) were obtained to estimate the association of individual polymorphisms and haplotypes with preeclampsia risk. No increase in the risk of preeclampsia for the intron-4 or –786T→C polymorphisms was observed under any model of inheritance. In contrast, in women homozygous for the Asp298 allele, the adjusted OR for preeclampsia was 4.60 (95% confidence interval [CI], 1.73 to 12.22) compared with carriers of the Glu298 allele. After a multivariate analysis, carriage of the “Asp298–786C-4b” haplotype was also associated with increased risk of preeclampsia (OR, 2.11 [95% CI, 1.33 to 3.34]) compared with carriers of the “Glu298–786T-4b” haplotype. The eNOS Glu298Asp polymorphism and the Asp298–786C-4b haplotype are risk factors for preeclampsia.
Quorum-Sensing-Negative (lasR) Mutants of Pseudomonas aeruginosa Avoid Cell Lysis and Death

ABSTRACT In Pseudomonas aeruginosa, N-acylhomoserine lactone signals regulate the expression of several hundreds of genes, via the transcriptional regulator LasR and, in part, also via the subordinate regulator RhlR. This regulatory network termed quorum sensing contributes to the virulence of P. aeruginosa as a pathogen. The fact that two supposed PAO1 wild-type strains from strain collections were found to be defective for LasR function because of independent point mutations in the lasR gene led to the hypothesis that loss of quorum sensing might confer a selective advantage on P. aeruginosa under certain environmental conditions. A convenient plate assay for LasR function was devised, based on the observation that lasR mutants did not grow on adenosine as the sole carbon source because a key degradative enzyme, nucleoside hydrolase (Nuh), is positively controlled by LasR. The wild-type PAO1 and lasR mutants showed similar growth rates when incubated in nutrient yeast broth at pH 6.8 and 37°C with good aeration. However, after termination of growth during 30 to 54 h of incubation, when the pH rose to ≥ 9, the lasR mutants were significantly more resistant to cell lysis and death than was the wild type. As a consequence, the lasR mutant-to-wild-type ratio increased about 10-fold in mixed cultures incubated for 54 h. In a PAO1 culture, five consecutive cycles of 48 h of incubation sufficed to enrich for about 10% of spontaneous mutants with a Nuh− phenotype, and five of these mutants, which were functionally complemented by lasR+, had mutations in lasR. The observation that, in buffered nutrient yeast broth, the wild type and lasR mutants exhibited similar low tendencies to undergo cell lysis and death suggests that alkaline stress may be a critical factor providing a selective survival advantage to lasR mutants.