Finding multiple target optimal intervention in disease-related molecular network

Drugs against multiple targets may overcome the many limitations of single targets and achieve a more effective and safer control of the disease. Numerous high-throughput experiments have been performed in this emerging field. However, systematic identification of multiple drug targets and their best intervention requires knowledge of the underlying disease network and calls for innovative computational methods that exploit the network structure and dynamics. Here, we develop a robust computational algorithm for finding multiple target optimal intervention (MTOI) solutions in a disease network. MTOI identifies potential drug targets and suggests optimal combinations of the target intervention that best restore the network to a normal state, which can be customer designed. We applied MTOI to an inflammation-related network. The well-known side effects of the traditional non-steriodal anti-inflammatory drugs and the recently recalled Vioxx were correctly accounted for in our network model. A number of promising MTOI solutions were found to be both effective and safer

Effect of laser heat treatment on structure and wear resistance of cobalt stellite

The structure and wear resistance of Stellite 6 alloy were studied before and after laser heat treatment. A significant refinement of the microstructure after the heat treatment is noted, the hardness the alloy changed slightly. An increase of wear resistance in shock-abrasive wear at angles of attack of 60-90° as well as metal-to-metal wear with presence of an abrasive layer is shown. © 2019 IOP Publishing Ltd. All rights reserved

Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies

Purpose Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Methods Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. Results The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus > 1–2.5 cm (1.45, 1.47), age ≥ 50 versus 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. Conclusions The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making

Modification of the Heat-Shielding Coatings Based on ZrO2 by the Spreading Method

A method has been developed for applying a heat-shielding coating based on zirconium dioxide reinforced with ceramic fiber by manually spreading an aqueous slip followed by drying and calcining at 1200°C in an inert atmosphere

STUDY OF MODIFIED HEAT-SHIELDING COATINGS BASED ON ZrO2

The methods for modifying heat-shielding coatings by applying a layer based on ZrO2 followed by drying and calcination at 1200°C in an inert atmosphere have been developed

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Current progress on removal of recalcitrance coloured particles from anaerobically treated effluent using coagulation–flocculation

The palm oil industry is the most important agro industries in Malaysia and most of the mills adopt anaerobic digestion as their primary treatment for palm oil mill effluent (POME). Due to the public concern, decolourisation of anaerobically treated POME (AnPOME) is becoming a great concern. Presence of recalcitrant-coloured particles hinders biological processes and coagulation–flocculation may able to remove these coloured particles. Several types of inorganic and polymers-based coagulant/flocculant aids for coagulation–flocculation of AnPOME have been reviewed. Researchers are currently interested in using natural coagulant and flocculant aids. Modification of the properties of natural coagulant and flocculant aids enhanced coagulation–flocculation performance. Modelling and optimization of the coagulation–flocculation process have also been reviewed. Chemical sludge has the potential for plant growth that can be evaluated through pot trials and phytotoxicity test

The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831

Introduction: The N9831 trial demonstrated the efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) locally positive tumors by protein or gene analysis. We used the 21-gene assay to examine the association of quantitative HER2 messenger RNA (mRNA) gene expression and benefit from trastuzumab. Methods: N9831 tested the addition of trastuzumab to chemotherapy in stage I-III HER2-positive breast cancer. For two of the arms of the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA expression were determined by the 21-gene assay (Oncotype DX®) (negative 2 expression units). Cox regression was used to assess the association of HER2 expression with trastuzumab benefit in preventing distant recurrence. Results: Median follow-up was 7.4years. Of 1,940 total patients, 901 had consent and sufficient tissue. HER2 by reverse transcriptase polymerase chain reaction (RT-PCR) was negative in 130 (14%), equivocal in 85 (9%), and positive in 686 (76%) patients. Concordance between HER2 assessments was 95% for RT-PCR versus central immunohistochemistry (IHC) (>10% positive cells = positive), 91% for RT-PCR versus central fluorescence in situ hybridization (FISH) (≥2.0 = positive) and 94% for central IHC versus central FISH. In the primary analysis, the association of HER2 expression by 21-gene assay with trastuzumab benefit was marginally nonsignificant (nonlinear p = 0.057). In hormone receptor-positive patients (local IHC) the association was significant (p = 0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 expression levels. Conclusions: Concordance among HER2 assessments by central IHC, FISH, and RT-PCR were similar and high. Association of HER2 mRNA expression with trastuzumab benefit as measured by time to distant recurrence was nonsignificant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in patients with either IHC-positive or FISH-positive tumors. Trend for benefit was observed also for the small groups of patients with negative results by any or all of the central assays. Trial registration: Clinicaltrials.gov NCT00005970. Registered 5 July 2000

THE SYNTHESIS OF CERAMIC ZrO2-Y2O3 FIBERS BY THE METHOD OF IMPREGNATION OF VISCOSE WOOL

The possibility of synthesis of ZrO2 - Y2O3 ceramic fibers by means of impregnation of viscose wool by solutions of zirconyl nitrate with the addition of yttrium nitrate and subse-quent high - temperature roasting was considered