Vibration absorbers for chatter suppression: A new analytical tuning methodology

Vibration absorbers have been widely used to suppress undesirable vibrations in machining operations, with a particular emphasis on avoiding chatter. However, it is well known that for vibration absorbers to function effectively their stiffness and damping must be accurately tuned based upon the natural frequency of the vibrating structure. For general vibration problems, suitable tuning strategies were developed by Den Hartog and Brock over 50 years ago. However, the special nature of the chatter stability problem means that this classical tuning methodology is no longer optimal. Consequently, vibration absorbers for chatter mitigation have generally been tuned using ad hoc methods, or numerical or graphical approaches. The present article introduces a new analytical solution to this problem, and demonstrates its performance using time domain milling simulations. A 40-50% improvement in the critical limiting depth of cut is observed, compared to the classically tuned vibration absorber. © 2006 Elsevier Ltd. All rights reserved

2017 Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update Implementation: Asia Summit Conference Report

Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD) 2009 provided recommendations on the detection, evaluation, and treatment of CKD-MBD in patients CKD who are and are not undergoing dialysis. Because of the accumulation of evidence since this initial publication, the CKD-MBD Guideline underwent a selective update in 2017. In April 2018, KDIGO convened a CKD-MBD Guideline Implementation Summit in Japan with the key objective to discuss various barriers to the uptake and implementation of the CKD-MBD Guideline in 8 Asian countries/regions. These countries/regions were comparable according to their high-to-middle economic ranking assigned by the World Bank. The discussion took into account the availability of CKD-MBD medication therapies and government health policies that may influence reimbursement and practice patterns in the region. Most importantly, Summit participants developed a framework of multifaceted strategies aimed at overcoming barriers to guideline implementation. The Summit attendees suggested a shared decision-making approach between clinicians and patients in CKD-MBD management, as well as individualized care based on the treatment risk-benefit ratio. The Summit participants also discussed how KDIGO, as a guideline development organization, may work in partnership with local and national nephrology societies to provide education and facilitate implementation of the guideline by clinicians. The conclusions drawn from this Summit in Asia may serve as an important guide for other regions to follow

The Effect of Selenium Supplementation in the Prevention of DNA Damage in White Blood Cells of Hemodialyzed Patients: A Pilot Study

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 μg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA

A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy

DNA damage and repair in endometrial cancer in correlation with the hOGG1 and RAD51 genes polymorphism

The cellular reaction to the DNA-damaging agents may modulate individual’s cancer susceptibility. This reaction is mainly determined by the efficacy of DNA repair, which in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphism. The hOGG1 gene encodes a glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both proteins can be involved in the repair of DNA lesions, which are known to contribute to endometrial cancer. In the present work we determined the extent of basal DNA damage and the efficacy of removal of DNA damage induced by hydrogen peroxide and N-methyl-N′-nitro N-nitrosoguanidyne (MNNG) in peripheral blood lymphocytes of 30 endometrial cancer patients and 30 individuals without cancer. The results from DNA damage and repair study were correlated with the genotypes of two common polymorphisms of the hOGG1 and RAD51 genes: a G>C transversion at 1245 position of the hOGG1 gene producing a Ser → Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G>C substitution at 135 position of the RAD51 gene (the 135G>C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis and genotypes were determined by restriction fragment length polymorphism PCR. We observed a strong association between endometrial cancer and the C/C genotype of the 135G>C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and endometrial cancer occurrence in subjects with a high level of basal DNA damage. We did not observe any correlation between the Ser326Cys polymorphism of the hOGG1 gene and endometrial cancer. Our result suggest that the 135G>C polymorphism of the RAD51 gene may be linked to endometrial cancer and can be considered as an additional marker of this disease

Epstein-Barr Virus BGLF4 Kinase Retards Cellular S-Phase Progression and Induces Chromosomal Abnormality

Epstein-Barr virus (EBV) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus. The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1. However, the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression. Here, we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells. Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae. Using time-lapse microscopy, we found the fate of individual HeLa cells was determined by the expression level of BGLF4. In addition to slight cell growth retardation, BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells. In Saos-2 cells, BGLF4 induced the hyperphosphorylation of co-transfected RB, while E2F1 was not released from RB-E2F1 complexes. The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner. Detection with phosphoamino acid specific antibodies revealed that, in addition to Ser780, phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4. Taken together, our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression