Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) ...assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults.
This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18–50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed.
Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five 20% with 0·67 mg, 11 44% with 2 mg, and seven 28% with 6 mg), and malaise or fatigue (five 20% with 0·67 mg, seven 28% with 2 mg, and two 8% with 6 mg). The most common local solicited symptoms were administration site pain (23 92% with all three doses) and tenderness (21 84% with all three doses). Most solicited symptoms were reported as mild (19 76% with 0·67 mg, 20 80% with 2 mg, and 17 68% with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively.
The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus.
US Department of the Army and GeneOne Life Science.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The development of unmanned aerial vehicles (UAVs) is expected to become one of the most commercialized research areas in the world over the next decade. Globally, unmanned aircraft have been ...increasingly used for safety surveillance in the construction industry and civil engineering fields. This paper presents an aerial image-based approach using UAVs to inspect cracks and deformations in buildings. A state-of-the-art safety evaluation method termed SMART SKY EYE (Smart building safety assessment system using UAV) is introduced; this system utilizes an unmanned airplane equipped with a thermal camera and programmed with various surveying efficiency improvement methods, such as thermography, machine-learning algorithms, and 3D point cloud modeling. Using this method, crack maps, crack depths, and the deformations of structures can be obtained. Error rates are compared between the proposed and conventional methods.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
There are no known specific therapies or vaccines to treat or prevent Zika virus infection. In this report, encouraging data are presented from a phase 1 study of a DNA vaccine against ZIKV infection.
We conducted a probabilistic evaluation of changes in coronary heart disease (CHD) risk and public health burdens from industrially produced trans-fatty acids (IP-TFAs) exposure from the uses of ...partially hydrogenated oils in food. Our analyses used four quantitative methods based on human studies considering the uncertainty associated with risk parameters for CHD and IP-TFA daily dietary exposure of 0.05% of energy. Method 1 used experimental controlled feeding trial data for changes in low-density lipoprotein cholesterol; Method 2 used changes in both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; Method 3 used changes in a combination of three emerging CHD risk factor biomarkers; and method 4 used prospective observational studies of CHD cases associated with long-term dietary exposure of trans-fatty acids. We estimated mean percent changes in CHD risk and annual CHD cases in U.S. adults, with lower and upper 95% uncertainty intervals. Our results show that consuming 0.05% of energy from IP-TFA, instead of cis-monounsaturated fatty acids, can cause annual mean increases in CHD cases of 814 (510-1151, method 1), 1502 (990-2043, method 2), or 6877 (3611-10 694, method 4) in U.S. adults. Results for method 3 were intermediate between those for methods 2 and 4. Sensitivity analyses using alternate risk parameters or an alternate exposure scenario resulted in minor changes in public health burden estimates. The results demonstrate that IP-TFA exposure as low as 0.05% of energy from partially hydrogenated oil uses in food can cause substantial public health burdens in the United States from increased CHD risk.
Varying coefficient regression models are known to be very useful tools for analysing the relation between a response and a group of covariates. Their structure and interpretability are similar to ...those for the traditional linear regression model, but they are more flexible because of the infinite dimensionality of the corresponding parameter spaces. The aims of this paper are to give an overview on the existing methodological and theoretical developments for varying coefficient models and to discuss their extensions with some new developments. The new developments enable us to use different amount of smoothing for estimating different component functions in the models. They are for a flexible form of varying coefficient models that requires smoothing across different covariates' spaces and are based on the smooth backfitting technique that is admitted as a powerful technique for fitting structural regression models and is also known to free us from the curse of dimensionality.
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BFBNIB, FZAB, GIS, IJS, INZLJ, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
Bioactive herbicidal compounds produced by soil microorganisms might be used to creating a bioherbicide for biological weed control. A total of 1,300 bacterial strains were isolated and screened for ...herbicidal activity against grass and broadleaf weeds. Among primarily selected 102 strains, the herbicidal activity of bacterial fermentation broths from the following three isolates strain-101, strain-128, and strain-329 reduced the growth of D. sanguinalis by 66.7%, 78.3%, and 100%, respectively as compared with control. Phylogenetic analysis of 16S rRNA gene sequencing determined that the strain-329 has 99% similarity to Streptomyces anulatus (HBUM 174206). The potential bioherbicidal efficacy of Streptomyces strain-329 was tested on grass and broadleaf weeds for phytotoxic activity through pre- and post-emergence applications. At pre-emergence application, the phytotoxic efficacy to D. sanguinalis and S. bicolor on seed germination were 90.4% and 81.3%, respectively at the 2x concentration, whereas in the case of Solanum nigrum, 85.2% phytotoxic efficacy was observed at the 4x concentration. The efficacy of Streptomyces strain-329 was substantially higher at post-emergence application, presenting 100% control of grass and broadleaf weeds at the 1x concentration. Two herbicidal compounds coded as 329-C1 and 329-C3 were extracted and purified by column chromatography and high-performance liquid chromatography methods. The active compound 329-C3 slightly increased leaf electrolytic leakage and MDA production as concentration-dependent manner. These results suggest that new Streptomyces sp. strain-329 produced bioherbicidal metabolites and may provide a new lead molecule for production an efficient bioherbicide to regulate grass and broadleaf weeds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Genome‐wide next‐generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies ...on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics.
Methods and results
Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC‐NOS). Panels of seven (PIK3CA, CDH1, PTEN, RHOA, HDCA9, KRAS, and ATM), three (PIK3CA, CTNNB1, and KRAS) and two (HDCA9 and IGF1R) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, PDGFRB mutations were associated with a favourable prognosis, whereas MET mutations were associated with a poor prognosis. The PCC‐NOS‐predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC‐predominant type. Mutations in TP53, BRAF, PI3CA, SMAD4 and RHOA were associated with PCC‐NOS. Interestingly, RHOA‐mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC‐NOS component with desmoplasia.
Conclusions
Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with RHOA mutation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In this era of the fourth industrial revolution, the integration of big data and 3D printing technology with the construction industry has maximized productivity. Currently, there is an active effort ...to research the optimal cladding structure through 3D printing technology to reduce production costs. This paper proposes a new type of 3D print curtain wall, using a high-strength ABS-M30 polymer panel, which is stronger than the standard acrylonitrile butadiene styrene (ABS) polymer, as an internally reinforced structure. This structure is fabricated via fused deposition modeling, a 3D printing method, to reduce the weight of the general cement panel. In addition, the shape of the polymer board was designed; three shapes were considered-O, W, and X types-which aided in further reducing the weight of the cladding. After comparing the center deformation of the structure through a lateral load test and finite element method analysis, the optimal model was selected. The measured data of the two methods at a design wind speed of 100% showed a difference of approximately 10%; however, at 150% of the design wind speed, the difference between the two sets of data increased to 27%.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background and Aim
Staining for hepatitis B viral antigens is often done in liver biopsies from patients with chronic hepatitis B, but its correlates with clinical phenotypes are not well described.
...Methods
Biopsies were collected from a large cohort of adults and children with chronic hepatitis B viral infection through the Hepatitis B Research Network. Immunohistochemical staining of sections was done for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) and then centrally read by the pathology committee. The degree of liver injury and pattern of staining were then correlated with clinical characteristics, including the clinical phenotype of hepatitis B.
Results
Biopsies from 467 subjects were studied, including 46 from children. Immunostaining for HBsAg was positive in 417 (90%) with scattered hepatocyte staining being the most common pattern. HBsAg staining correlated best with serum levels of HBsAg and hepatitis B viral DNA; the absence of HBsAg staining was often a prelude to loss of HBsAg from serum. HBcAg staining was positive in 225 (49%), and, while cytoplasmic staining was more frequent than nuclear staining, both nuclear and cytoplasmic positivity were often seen in the same specimen. Staining for HBcAg correlated with both level of viremia and liver injury. No biopsies from inactive carriers had stainable HBcAg, while 91% of the biopsies from those with hepatitis B e antigen‐positive chronic hepatitis B stained positively for HBcAg.
Conclusion
Immunostaining for hepatitis B viral antigens may yield helpful insights into liver disease pathogenesis but appears to add little to commonly used serological and biochemical blood tests.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Previous studies have documented student–faculty interaction in STEM, but fewer studies have specifically studied negative forms of interaction such as discrimination from faculty. Using a sample of ...562 STEM undergraduates from the National Longitudinal Survey of Freshmen, we use hierarchical generalized linear modeling to investigate various types of student–faculty interaction in Science, Technology, Engineering, and Math (STEM) and in particular, the link between discrimination from faculty and retention in STEM. While Black students interacted more frequently with faculty, they were also most likely to report experiencing racial/ethnic discrimination. Overall, female, Black, and Latinx students were more likely to leave STEM by the fourth year of college than male, White, and Asian American peers. Feeling that professors made a student feel uncomfortable due to race/ethnicity was negatively linked with STEM retention. None of the traditional forms of student–faculty interaction (i.e., non-discriminatory) predicted retention. Variation in patterns by race, gender, and income are discussed, as well as implications for research, policy, and practice.
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BFBNIB, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ, ZRSKP
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