Associations between Benign Cutaneous Nevi and Risk of Type 2 Diabetes Mellitus in Men and Women: Results from Two Prospective Cohort Studies

poster abstractABSTRACT Objective: Previous studies suggest that the number of cutaneous nevi and type 2 diabetes mellitus (T2DM) are both associated with endogenous sex hormone levels. However, no prospective studies have specifically examined the relationship between the number of benign cutaneous nevi and T2DM. Research Design and Methods: We prospectively examined the associations between the number of nevi and risk of T2DM among 23,748 men (1986-2010) from the Health Professionals Follow-up Study (HPFS) and 67,050 women (1989-2010) from the Nurses' Health Study (NHS). Information on the numbers of melanocytic nevi on arms and the incidence of T2DM was collected by validated questionnaires. Results: During 1,831,118 person-years of follow-up, we documented 8748 incident cases of T2DM. After adjustment for age, BMI, and other diabetes risk factors, the number of nevi was significantly associated with increased risk of T2DM. Multivariable-adjusted HRs (95% CIs) for <1, 1-5, 6-14, and ≥15 nevi were 1.00 (reference), 1.02 (0.92, 1.14), 1.10 (0.87, 1.38), and 1.70 (1.22, 2.36), respectively, for men (P trend = 0.03) and 1.00 (reference), 1.15 (1.09, 1.21), 1.25 (1.11, 1.40), and 1.70 (1.38, 2.09), respectively, for women (P trend = 0.019). This positive association remained consistent across subgroups of participants. Conclusions: Mole count may represent a novel marker for development of T2DM in men and women, indicating a unique nevus development-related mechanism, possibly due to altered levels or functions of endogenous steroid sex hormones, in the pathogenesis of T2DM. Further studies are warranted to clarify the relationship of nevogenesis and T2DM and underlying mechanisms

Fatigue life prediction of 5083 and 5A06 aluminum alloy T-welded joints based on the fatigue characteristics domain

Three-point bending fatigue test of 5083 and 5A06 aluminum alloy T-welded joints is carried out, and the fatigue life of the specimens with different influencing factors are obtained. Finite element model of the T-welded joint is established and the nodal force based structural stress is calculated. Neighborhood rough set theory is used for analysis of the factors which influence the fatigue life of the aluminum alloy welded joints. Key influencing factors are studied and the fatigue characteristic domains are determined. The master S-N curve characterized by the nodal force based structural stress range and cycles to failure on semi log coordinate as well as S-N curves corresponding to the fatigue characteristic domain is fitted. A case study of fatigue life prediction of 5A06 aluminum alloy welded joint indicates the effectiveness of the fatigue life prediction method based on the fatigue characteristic domain

Fatigue life prediction of 5083 and 5A06 aluminum alloy T-welded joints based on the fatigue characteristics domain

Three-point bending fatigue test of 5083 and 5A06 aluminum alloy T-welded joints is carried out, and the fatigue life of the specimens with different influencing factors are obtained. Finite element model of the T-welded joint is established and the nodal force based structural stress is calculated. Neighborhood rough set theory is used for analysis of the factors which influence the fatigue life of the aluminum alloy welded joints. Key influencing factors are studied and the fatigue characteristic domains are determined. The master S-N curve characterized by the nodal force based structural stress range and cycles to failure on semi log coordinate as well as S-N curves corresponding to the fatigue characteristic domain is fitted. A case study of fatigue life prediction of 5A06 aluminum alloy welded joint indicates the effectiveness of the fatigue life prediction method based on the fatigue characteristic domain

Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Carbon Fiber Prepreg Composites Failure Mechanism Based on Electrical Resistance Method during Hight-Strain Rate Loading

In this study, a unidirectional and plain weave carbon fiber/epoxy prepreg was used as the raw material, and the prepreg tape winding process was used to prepare carbon fiber/epoxy prepreg composites with 65% and 75% carbon fiber volume content, respectively. Based on traditional damage experiments and mechanical measurements, electrical measurements are introduced to study the damage to carbon fiber prepreg composites. The damage behavior of the carbon fiber prepreg composite under a high-speed impact load was monitored using the resistance method. By arranging electrodes on the sample and tracking the change in resistance during the entire process of high-speed impact of the material, the relationship between the damage and the change in resistance parameters of the carbon fiber prepreg composite winding products under high-speed impact was determined. The stress-strain curve and the final failure mode of the sample and the microstructure mechanics of carbon fiber prepreg winding products under different strain rates were analyzed. These results indicate that, as the change in resistance over time was almost stable from 0 to 200 &mu;s. From 200 to 250 &mu;s, the resistance decreases sharply; from 250 to 400 &mu;s, the resistance approximates a plateau. From 400 to 500 &mu;s, the resistance value increases again; at this time, the resistance value decreases to 3.2% of the initial resistance value

Investigation of the Self-Heating of Q460 Butt Joints and an S-N Curve Modeling Method Based on Infrared Thermographic Data for High-Cycle Fatigue

In this study, we investigated the fatigue behavior of Q460 welded joints using tensile fatigue tests. Furthermore, real-time temperature profiles of the examined specimens were recorded by infrared thermography. Based on the obtained thermographic data, we calculated the entropy production rate of the specimens under different stress amplitudes. Hypothetically, the entropy production during high-cycle fatigue (HCF) could be divided into two parts. The first is induced by inelastic behavior that corresponds to damage accumulation, and the second originates from anelasticity associated with recoverable non-damaging microstructural motions. The turning point of entropy production under different stress levels represents an index for fatigue limit estimation. Then, considering the average damage threshold that exists during HCF, the entropy production related to damage accumulation (cumulative damage entropy) is obtained by testing three specimens under the same stress amplitude above the fatigue limit. Finally, a rapid three-parameter S-N curve with a survival probability rate of 50% is obtained. Then, combined with the maximum likelihood method, the 5% and 95% survival probability rate S-N curves are established. Most of experimental data are distributed in the area between S-N curves that correspond to 5% and 95% survival probability rate, indicating good accordance with the test data

A Real-Time BLE/PDR Integrated System by Using an Improved Robust Filter for Indoor Position

Indoor position technologies have attracted the attention of many researchers. To provide a real-time indoor position system with high precision and stability is necessary under many circumstances. In a real-time position scenario, gross errors of the Bluetooth low energy (BLE) fingerprint method are more easily occurring and the heading angle of the pedestrian will drift without acceleration and magnetic field compensation. A real-time BLE/pedestrian dead-reckoning (PDR) integrated system by using an improved robust filter has been proposed. In the PDR method, the improved Mahony complementary filter based on the pedestrian motion states is adopted to estimate the heading angle reducing the drift error. Then, an improved robust filter is utilized to detect and restrain the gross error of the BLE fingerprint method. The robust filter detected the gross error at different granularity by constructing a robust vector changing the observation covariance matrix of the extended Kalman filter (EKF) adaptively when the application is running. Several experiments are conducted in the true position scenario. The mean position accuracy obtained by the proposed method in the experiment is 0.844 m and RMSE is 0.74 m. Compared with the classic EKF, these two values are increased by 38% and 18%, respectively. The results show that the improved filter can avoid the gross error in the BLE method and provide high precision and scalability in indoor position service

Isolation and Identification of Pentalenolactone Analogs from Streptomyces sp. NRRL S-4

Terpene synthases are widely distributed in Actinobacteria. Genome sequencing of Streptomyces sp. NRRL S-4 uncovered a biosynthetic gene cluster (BGC) that putatively synthesizes pentalenolactone type terpenes. Guided by genomic information, the S-4 strain was chemically investigated, resulting in the isolation of two new sesquiterpenoids, 1-deoxy-8&alpha;-hydroxypentalenic acid (1) and 1-deoxy-9&beta;-hydroxy-11-oxopentalenic acid (2), as shunt metabolites of the pentalenolactone (3) biosynthesis pathway. Their structures and absolute configurations were elucidated by analyses of HRESIMS and NMR spectroscopic data as well as time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Compounds 1 and 2 exhibited moderate antimicrobial activities against Gram-positive and Gram-negative bacteria. These results confirmed that the pentalenolactone pathway was functional in this organism and will facilitate efforts for exploring Actinobacteria using further genome mining strategies