Influence of the Kinematic System on the Geometrical and Dimensional Accuracy of Holes in Drilling

This article attempts to show how the kinematic system affects the geometrical and dimensional accuracy of through-holes in drilling. The hole cutting tests were performed using a universal turning center. The tool was a TiAlN-coated Ø 6 mm drill bit, while the workpiece was a C45 steel cylinder with a diameter of 30 mm and a length of 30 mm. Three kinematic systems were studied. The first consisted of a fixed workpiece and a rotating and linearly moving tool. In the second, the workpiece rotated, while the tool moved linearly. The third system comprised a rotating workpiece and a rotating and linearly moving tool, but they rotated in opposite directions. The geometrical and dimensional accuracy of the hole was assessed by analyzing the cylindricity, straightness, roundness, and diameter errors. The experiment was designed using the Taguchi orthogonal array method to determine the significance of the effects of the input parameters (cutting speed, feed per revolution, and type of kinematic system) on the accuracy errors. A multifactorial statistical analysis (ANOVA) was employed for this purpose. The study revealed that all the input parameters considered had a substantial influence on the hole quality in drilling.     

Modification of Lightweight Aggregate Concretes with Silica Nanoparticles—A Review

The use of lightweight concrete (LWC) for structural and non-structural applications has attracted great interest in recent years. The main benefits include reduced deadload of structural elements and generally lower production and transportation costs. However, a decrease in concrete density often leads to a decrease in strength and durability. Typically, concretes are mostly modified with mineral additives such as silica fume or fly ash. Because of the recent developments in nanotechnology, research attention has turned to the possibility of improving concrete properties with nanomaterials, i.e., nano-SiO₂. However, there are still certain issues with the dosage and efficiency of nanomaterials. Therefore, in order to establish the current state of knowledge in this field, this review gathers most recent results about the performance of LWC modified with nanomaterials. The review is divided into sections about the influence of nanoparticles on the fresh properties of concrete and their influence on the mechanical and durability characteristics. The paper studies in depth the most common approach to nanomaterials in concrete technology and proposes areas for further development.     

Concentration- and time-dependent behavioral changes in Caenorhabditis elegans after exposure to nicotine

Nicotine induces profound behavioral responses in the model organism Caenorhabditis elegans. We tested the effect of a broad range of concentrations of nicotine (from 0.001 mM to 30 mM in nematode growth medium) on C. elegans locomotor behavior. We also followed the time-course influence on the sensitivity of C. elegans to nicotine (from 0 min to 300 min). A low concentration (0.001 mM) of this alkaloid causes a reduction of the speed of movement. By contrast, moderate concentrations (0.01 and 0.1 mM) induced acceleration of the mean speed of locomotion of C. elegans. High doses of nicotine (above 1 mM) induced slowing down of the movements and, finally, paralysis. Time-dependent analysis revealed that the stimulating effect of nicotine abolished the slowing down of C. elegans in control experiments after 30 min in the presence of 0.001, 0.1 and 10 mM nicotine. In the presence of 0.1 mM nicotine, the stimulation phase lasted up to 70 min. The evidence indicates that nicotine can have dual effects on the speed of locomotion, which is dependent on differences in its dosage and treatment time.     

Imatinib sensitivity in BCR-ABL1-positive chronic myeloid leukemia cells is regulated by the remaining normal ABL1 allele

Chronic myeloid leukemia in chronic phase (CML-CP) cells that harbor oncogenic BCR-ABL1 and normal ABL1 allele often become resistant to the ABL1 kinase inhibitor imatinib. Here, we report that loss of the remaining normal ABL1 allele in these tumors, which results from cryptic interstitial deletion in 9q34 in patients who did not achieve a complete cytogenetic remission (CCyR) during treatment, engenders a novel unexpected mechanism of imatinib resistance. BCR-ABL1-positive Abl1(-/-) leukemia cells were refractory to imatinib as indicated by persistent BCR-ABL1-mediated tyrosine phosphorylation, lack of BCR-ABL1 protein degradation, increased cell survival, and clonogenic activity. Expression of ABL1 kinase, but not a kinase-dead mutant, restored the antileukemic effects of imatinib in ABL1-negative chronic myelogenous leukemia (CML) cells and in BCR-ABL1-positive Abl1(-/-) murine leukemia cells. The intracellular concentration of imatinib and expression of its transporters were not affected, although proteins involved in BCR-ABL1 degradation were downregulated in Abl1(-/-) cells. Furthermore, 12 genes associated with imatinib resistance were favorably deregulated in Abl1(-/-) leukemia. Taken together, our results indicate that loss of the normal ABL1 kinase may serve as a key prognostic factor that exerts major impact on CML treatment outcomes.     

CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers

Objectives

Pantoprazole is metabolized by cytochrome P450 2?C19, which shows genetic polymorphism. The effect of CYP2C19 polymorphism on single-dose pharmacokinetics of oral pantoprazole in healthy volunteers was evaluated.

Methods

Pantoprazole pharmacokinetics was determined in 32 healthy volunteers after a 40-mg single oral dose of the drug.

Results

Carriers of CYP2C19*2/*2 (n?=?2) were characterized by higher, starting from 3.5?h post dose, plasma concentrations of pantoprazole in comparison to wild-type (CYP2C19*1/*1, n?=?6) volunteers. In subjects with CYP2C19*17/*17 genotype (n?=?6) significantly lower plasma concentrations of the drug vs CYP2C19*1/*1 carriers, were observed from 3.0?h after oral pantoprazole administration. Carriers of CYP2C19*1/*17 (n?=?6) and CYP2C19*2/*17 (n?=?6) displayed concentration–time profiles comparable to wild-type subjects. CYP2C19*2/*2 volunteers showed a decrease in terminal elimination rate constant (λ_z) by 83.3%, prolongation of terminal half-life (t_?) by 572%, a rise in area under the concentration–time curve (AUC) and mean residence time (MRT) by 506% and 259% respectively. Heterozygotes, i.e.. CYP2C19*1/*2 vs CYP2C19*1/*1 were characterized by higher AUC (4.38?±?1.00?mg?h/L vs 3.00?±?1.02 mg?h/L, p?max (2.13?±?0.42?mg/L vs 1.61?±?0.35?mg/L, p?p?CYP2C19*17/*17 vs CYP2C19*1/*1 genotypes was observed. Population modeling confirmed the influence of *1/*2, *2/*2, and *17/*17 genotypes on the pharmacokinetics of pantoprazole. The lowest population oral clearance was assessed in the carriers of genotype *2/*2 (3.68?L/h) and the highest value in subjects with genotype *17/*17 (31.13?L/h).

Conclusion

These data suggest that CYP2C19 polymorphism is an important determinant of pantoprazole pharmacokinetics.     

Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide

Purpose  

Leflunomide (LEF) is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA) and the action of which may be modified by sex hormones. The aim of this study was to examine the association between CAG repeat polymorphism in the androgen receptor (AR) gene and the response to treatment with LEF in women with RA.     

Blood and Hair Aluminum Levels,Vaccine History,and Early Infant Development: A Cross-Sectional Study

Objective

To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunization history and development.

Multivariate analysis as an advantageous approach for prediction of the adverse outcome in head and neck microvascular reconstructive surgery

Background

The use of a free flap has become a mainstay of reconstruction following the ablative surgery in head and neck. The success rates are about 90%, however, several factors have been described to have an adverse effect on free flap survival.

Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion

Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.