Search results for: George Zhou

Authors: Sachil Kumar, Anoop K.Verma, Uma Shankar Singh

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It’s extremely important to study postmortem interval in different causes of death since it assists in a great way in making an opinion on the exact cause of death following such incident often times. With diligent knowledge of the interval one could really say as an expert that the cause of death is not feigned hence there is a great need in evaluating such death to have been at the CRIME SCENE before performing an autopsy on such body. The approach described here is based on analyzing the degradation or proteolysis of a cardiac protein in cases of deaths due to burn as a marker of time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (Department of Forensic Medicine and Toxicology), King George’s Medical University, Lucknow India, after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC) for different time periods (~7.30, 18.20, 30.30, 41.20, 41.40, 54.30, 65.20, and 88.40 Hours). The cases included were the subjects of burn without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. As time postmortem progresses the intact cTnT band degrades to fragments that are easily detected by the monoclonal antibodies. A decreasing trend in the level of cTnT (% of intact) was found as the PM hours increased. A significant difference was observed between <15 h and other PM hours (p<0.01). Significant difference in cTnT level (% of intact) was also observed between 16-25 h and 56-65 h & >75 h (p<0.01). Western blot data clearly showed the intact protein at 42 kDa, three major (28 kDa, 30kDa, 10kDa) fragments, three additional minor fragments (12 kDa, 14kDa, and 15 kDa) and formation of low molecular weight fragments. Overall, both PMI and cardiac tissue of burned corpse had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 41.40 Hrs and after it intact protein slowly disappears. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the time postmortem. A strong significant positive correlation was found between cTnT and PM hours (r=0.87, p=0.0001). The regression analysis showed a good variability explained (R2=0.768) The post-mortem Troponin-T fragmentation observed in this study reveals a sequential, time-dependent process with the potential for use as a predictor of PMI in cases of burning.

Keywords: burn, degradation, postmortem interval, troponin-T

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Authors: Anastasia Beketova, Emmanouil-George C. Tzanakakis, Ioannis G. Tzoutzas, Eleana Kontonasaki

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In restorative dentistry, yttria-stabilized zirconia (YSZ) nanoparticles can be applied as fillers to improve the mechanical properties of various resin-based materials. Using sol-gel based synthesis as simple and cost-effective method, nano-sized YSZ particles with high purity can be produced. The aim of this study was to synthesize YSZ nanoparticles by the Pechini sol-gel method at different temperatures and to investigate their composition, structure, and morphology. YSZ nanopowders were synthesized by the sol-gel method using zirconium oxychloride octahydrate (ZrOCl₂.8H₂O) and yttrium nitrate hexahydrate (Y(NO₃)₃.6H₂O) as precursors with the addition of acid chelating agents to control hydrolysis and gelation reactions. The obtained powders underwent TG_DTA analysis and were sintered at three different temperatures: 800, 1000, and 1200°C for 2 hours. Their composition and morphology were investigated by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction Analysis (XRD), Scanning Electron Microscopy with associated with Energy Dispersive X-ray analyzer (SEM-EDX), Transmission Electron Microscopy (TEM) methods, and Dynamic Light Scattering (DLS). FTIR and XRD analysis showed the presence of pure tetragonal phase in the composition of nanopowders. By increasing the calcination temperature, the crystallinity of materials increased, reaching 47.2 nm for the YSZ1200 specimens. SEM analysis at high magnifications and DLS analysis showed submicron-sized particles with good dispersion and low agglomeration, which increased in size as the sintering temperature was elevated. From the TEM images of the YSZ1000 specimen, it can be seen that zirconia nanoparticles are uniform in size and shape and attain an average particle size of about 50 nm. The electron diffraction patterns clearly revealed ring patterns of polycrystalline tetragonal zirconia phase. Pure YSZ nanopowders have been successfully synthesized by the sol-gel method at different temperatures. Their size is small, and uniform, allowing their incorporation of dental luting resin cements to improve their mechanical properties and possibly enhance the bond strength of demanding dental ceramics such as zirconia to the tooth structure. This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme 'Human Resources Development, Education and Lifelong Learning 2014- 2020' in the context of the project 'Development of zirconia adhesion cements with stabilized zirconia nanoparticles: physicochemical properties and bond strength under aging conditions' (MIS 5047876).

Keywords: dental cements, nanoparticles, sol-gel, yttria-stabilized zirconia, YSZ

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Authors: Laura Lee Prather

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A functioning democracy is defined by various characteristics, including freedom of speech, equality, human rights, rule of law and many more. Lawsuits brought to intimidate speakers, drain the resources of community members, and silence journalists and others who speak out in support of matters of public concern are an abuse of the legal system and an encroachment of human rights. The impact can have a broad chilling effect, deterring others from speaking out against abuse. This article aims to suggest ways to address this form of judicial harassment. In 1988, University of Denver professors George Pring and Penelope Canan coined the term “SLAPP” when they brought to light a troubling trend of people getting sued for speaking out about matters of public concern. Their research demonstrated that thousands of people engaging in public debate and citizen involvement in government have been and will be the targets of multi-million-dollar lawsuits for the purpose of silencing them and dissuading others from speaking out in the future. SLAPP actions chill information and harm the public at large. Professors Pring and Canan catalogued a tsunami of SLAPP suits filed by public officials, real estate developers and businessmen against environmentalists, consumers, women’s rights advocates and more. SLAPPs are now seen in every region of the world as a means to intimidate people into silence and are viewed as a global affront to human rights. Anti-SLAPP laws are the antidote to SLAPP suits and while commonplace in the United States are only recently being considered in the EU and the UK. This researcher studied more than thirty years of Anti-SLAPP legislative policy in the U.S., the call for evidence and resultant EU Commission’s Anti-SLAPP Directive and Member States Recommendations, the call for evidence by the UK Ministry of Justice, response and Model Anti-SLAPP law presented to UK Parliament, as well as, conducted dozens of interviews with NGO’s throughout the EU, UK, and US to identify varying approaches to SLAPP lawsuits, public policy, and support for SLAPP victims. This paper identifies best practices taken from the US, EU and UK that can be implemented globally to help combat SLAPPs by: (1) raising awareness about SLAPPs, how to identify them, and recognizing habitual abusers of the court system; (2) engaging governments in the policy discussion in combatting SLAPPs and supporting SLAPP victims; (3) educating judges in recognizing SLAPPs an general training on encroachment of human rights; (4) and holding lawyers accountable for ravaging the rule of law.

Keywords: Anti-SLAPP Laws and Policy, Comparative media law and policy, EU Anti-SLAPP Directive and Member Recommendations, International Human Rights of Freedom of Expression

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Authors: Shi-Bo Feng, Sheng-Jie Zhang, Jin Zhou

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The relationship between microbial diversity and algal bloom has received considerable attention for decades. Microbes undoubtedly affect annual bloom events and impact the physiology of both partners, as well as shape ecosystem diversity. However, knowledge about interactions and network correlations among broader-spectrum microbes that lead to the dynamics in a complete bloom cycle are limited. In this study, pyrosequencing and network approaches simultaneously assessed the associate patterns among bacteria, archaea, and microeukaryotes in surface water and sediments in response to a natural dinoflagellate (Alexandrium sp.) bloom. In surface water, among the bacterial community, Gamma-Proteobacteria and Bacteroidetes dominated in the initial bloom stage, while Alpha-Proteobacteria, Cyanobacteria, and Actinobacteria become the most abundant taxa during the post-stage. In the archaea biosphere, it clustered predominantly with Methanogenic members in the early pre-bloom period while the majority of species identified in the later-bloom stage were ammonia-oxidizing archaea and Halobacteriales. In eukaryotes, dinoflagellate (Alexandrium sp.) was dominated in the onset stage, whereas multiply species (such as microzooplankton, diatom, green algae, and rotifera) coexistence in bloom collapse stag. In sediments, the microbial species biomass and richness are much higher than the water body. Only Flavobacteriales and Rhodobacterales showed a slight response to bloom stages. Unlike the bacteria, there are small fluctuations of archaeal and eukaryotic structure in the sediment. The network analyses among the inter-specific associations show that bacteria (Alteromonadaceae, Oceanospirillaceae, Cryomorphaceae, and Piscirickettsiaceae) and some zooplankton (Mediophyceae, Mamiellophyceae, Dictyochophyceae and Trebouxiophyceae) have a stronger impact on the structuring of phytoplankton communities than archaeal effects. The changes in population were also significantly shaped by water temperature and substrate availability (N & P resources). The results suggest that clades are specialized at different time-periods and that the pre-bloom succession was mainly a bottom-up controlled, and late-bloom period was controlled by top-down patterns. Additionally, phytoplankton and prokaryotic communities correlated better with each other, which indicate interactions among microorganisms are critical in controlling plankton dynamics and fates. Our results supplied a wider view (temporal and spatial scales) to understand the microbial ecological responses and their network association during algal blooming. It gives us a potential multidisciplinary explanation for algal-microbe interaction and helps us beyond the traditional view linked to patterns of algal bloom initiation, development, decline, and biogeochemistry.

Keywords: microbial community, harmful algal bloom, ecological process, network

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Authors: Sundaresan Soundararajan, George Ezekiel Silvananthan, Chor Ngee Tan

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Introduction: Transforaminal Interbody Fusion (TLIF) has been adopted for many decades now, however, XLIF, still in relative infancy, has grown to be accepted as a new Minimally Invasive Surgery (MIS) option. There is a paucity of reports directly comparing lateral approach surgery to other MIS options such as TLIF in the treatment of lumbar degenerative disc diseases. Aims/Objectives: The objective of this study was to compare the efficacy and clinical outcomes between Minimally Invasive Transforaminal Interbody Fusion (TLIF) and Minimally Invasive Lateral Interbody Fusion (XLIF) in the treatment of patients with degenerative disc disease of the lumbar spine. Methods: A single center, retrospective cohort study involving a total of 38 patients undergoing surgical intervention between 2010 and 2013 for degenerative disc disease of lumbar spine at single L4/L5 level. 18 patients were treated with MIS TLIF, and 20 patients were treated with XLIF. Results: The XLIF group showed shorter duration of surgery compared to the TLIF group (176 mins vs. 208.3 mins, P = 0.03). Length of hospital stay was also significantly shorter in XLIF group (5.9 days vs. 9 days, p = 0.03). Intraoperative blood loss was favouring XLIF as 85% patients had blood loss less than 100cc compared to 58% in the TLIF group (P = 0.03). Radiologically, disc height was significantly improved post operatively in the XLIF group compared to the TLIF group (0.56mm vs. 0.39mm, P = 0.01). Foraminal height increment was also higher in the XLIF group (0.58mm vs. 0.45mm , P = 0.06). Clinically, back pain and leg pain improved in 85% of patients in the XLIF group and 78% in the TLIF group. Post op hip flexion weakness was more common in the XLIF group (40%) than in the TLIF group (0%). However, this weakness resolved within 6 months post operatively. There was one case of dural tear and surgical site infection in the TLIF group respectively and none in the XLIF group. Visual Analog Scale (VAS) score 6 months post operatively showed comparable reduction in both groups. TLIF group had Owsterty Disability Index (ODI) improvement on 67% while XLIF group showed improvement of 70% of its patients. Conclusions: Lateral approach surgery shows comparable clinical outcomes in resolution of back pain and radiculopathy to conventional MIS techniques such as TLIF. With significantly shorter duration of surgical time, minimal blood loss and shorter hospital stay, XLIF seems to be a reasonable MIS option compared to other MIS techniques in treating degenerative lumbar disc diseases.

Keywords: extreme lateral interbody fusion, lateral approach, minimally invasive, XLIF

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Authors: Ming Zhou, Taeho Park

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Early stage technologies have been particularly challenging to manage due to high degrees of their numerous uncertainties. Most research results directly out of a research lab tend to be at their early, if not the infant stage. A long while uncertain commercialization process awaits these lab results. The majority of such lab technologies go nowhere and never get commercialized due to various reasons. Any efforts or financial resources put into managing these technologies turn fruitless. High stake naturally calls for better results, which make a patenting decision harder to make. A good and well protected patent goes a long way for commercialization of the technology. Our preliminary research showed that there was not a simple yet productive procedure for such valuation. Most of the studies now have been theoretical and overly comprehensive where practical suggestions were non-existent. Hence, we attempted to develop a simple and highly implementable procedure for efficient and scalable valuation. We thoroughly reviewed existing research, interviewed practitioners in the Silicon Valley area, and surveyed university technology offices. Instead of presenting another theoretical and exhaustive research, we aimed at developing a practical guidance that a government agency and/or university office could easily deploy and get things moving to later steps of managing early stage technologies. We provided a procedure to thriftily value and make the patenting decision. A patenting index was developed using survey data and expert opinions. We identified the most important factors to be used in the patenting decision using survey ratings. The rating then assisted us in generating good relative weights for the later scoring and weighted averaging step. More importantly, we validated our procedure by testing it with our practitioner contacts. Their inputs produced a general yet highly practical cut schedule. Such schedule of realistic practices has yet to be witnessed our current research. Although a technology office may choose to deviate from our cuts, what we offered here at least provided a simple and meaningful starting point. This procedure was welcomed by practitioners in our expert panel and university officers in our interview group. This research contributed to our current understanding and practices of managing early stage technologies by instating a heuristically simple yet theoretical solid method for the patenting decision. Our findings generated top decision factors, decision processes and decision thresholds of key parameters. This research offered a more practical perspective which further completed our extant knowledge. Our results could be impacted by our sample size and even biased a bit by our focus on the Silicon Valley area. Future research, blessed with bigger data size and more insights, may want to further train and validate our parameter values in order to obtain more consistent results and analyze our decision factors for different industries.

Keywords: technology management, early stage technology, patent, decision

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Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li

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Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.

Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry

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Authors: Dechao Meng, Yongqi Dong, Qiyuan Feng, Zhangzhang Cui, Xiang Hu, Haoliang Huang, Genhao Liang, Huanhua Wang, Hua Zhou, Hawoong Hong, Jinghua Guo, Qingyou Lu, Xiaofang Zhai, Yalin Lu

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Great efforts have been taken to reveal the intrinsic origins of emerging ferromagnetism (FM) in strained LaCoO₃ (LCO) films. However, some macro magnetic performances of LCO are still not well understood and even controversial, such as magnetic anisotropy. Determining and understanding magnetic anisotropy might help to find the true causes of FM in turn. Perpendicular magnetic anisotropy (PMA) was the first time to be directly observed in high-quality LCO films with different thickness. The in-plane (IP) and out of plane (OOP) remnant magnetic moment ratio of 30 unit cell (u.c.) films is as large as 20. The easy axis lays in the OOP direction with an IP/OOP coercive field ratio of 10. What's more, the PMA could be simply tuned by changing the thickness. With the thickness increases, the IP/OOP magnetic moment ratio remarkably decrease with magnetic easy axis changing from OOP to IP. Such a huge and tunable PMA performance exhibit strong potentials in fundamental researches or applications. What causes PMA is the first concern. More OOP orbitals occupation may be one of the micro reasons of PMA. A cluster-like magnetic domain pattern was found in 30 u.c. with no obvious color contrasts, similar to that of LaAlO₃/SrTiO₃ films. And the nanosize domains could not be totally switched even at a large OOP magnetic field of 23 T. It indicates strong IP characters or none OOP magnetism of some clusters. The IP magnetic domains might influence the magnetic performance and help to form PMA. Meanwhile some possible nonmagnetic clusters might be the reason why the measured moments of LCO films are smaller than the calculated values 2 μB/Co, one of the biggest confusions in LCO films.What tunes PMA seems much more interesting. Totally different magnetic domain patterns were found in 180 u.c. films with cluster magnetic domains surrounded by < 110 > cross-hatch lines. These lines were regarded as structure domain walls (DWs) determined by 3D reciprocal space mapping (RSM). Two groups of in-plane features with fourfold symmetry were observed near the film diffraction peaks in (002) 3D-RSM. One is along < 110 > directions with a larger intensity, which is well match the lines on the surfaces. The other is much weaker and along < 100 > directions, which is from the normal lattice titling of films deposited on cubic substrates. The < 110 > domain features obtained from (103) and (113) 3D-RSMs exhibit similar evolution of the DWs percentages and magnetic behavior. Structure domains and domain walls are believed to tune PMA performances by transform more IP magnetic moments to OOP. Last but not the least, thick films with lots of structure domains exhibit different electrical transport behaviors. A metal-to-insulator transition (MIT) and an angular dependent negative magnetic resistivity were observed near 150 K, higher than FM transition temperature but similar to that of spin-orbital coupling related 1/4 order diffraction peaks.

Keywords: structure domain, magnetic anisotropy, magnetic domain, domain wall, 3D-RSM, strain

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Authors: Adae Amoako, Daniel Montero, Peter Murray, George Pujalte

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We present a case of a 42-year-old, right-handed Caucasian male who presented to a medical orthopedics clinic with left wrist pain. The patient indicated that the pain started two months prior to the visit. He could only remember helping a friend move furniture prior to the onset of pain. Examination of the left wrist showed limited extension compared to the right. There was clicking with flexion and extension of the wrist on the dorsal aspect. Mild tenderness was noticed over the distal radioulnar joint. There was ulnar and radial deviation on provocation. Initial 4-view x-rays of the left wrist showed mild radiocarpal and scapho-trapezium-trapezoid (ST-T) osteoarthritis, with subchondral cysts seen in the lunate and scaphoid, with no obvious fractures. The patient was initially put in a wrist brace and diclofenac topical gel was prescribed for pain control, as a patient could not take non-steroidal anti-inflammatory drugs (NSAIDs) due to gastritis. Despite diclofenac topical gel use and bracing, symptoms remained, and a steroid injection with 1 mL of lidocaine with 10 mg of triamcinolone acetonide was performed under fluoroscopy. He obtained some relief but after 3 months, the injection had to be repeated. On 2-month follow up after the initial evaluation, symptoms persisted. Magnetic resonance imaging (MRI) was obtained which showed an abnormal T1 hypodense signal involving the proximal pole of the scaphoid and articular collapse proximally of the scaphoid, with marked irregularity of the overlying cartilage, suggesting a remote injury, findings consistent with avascular necrosis of the proximal pole of the scaphoid. A month after that, the patient had the left proximal pole of the scaphoid debrided and an intercompartmental supraretinacular artery vascularized. Pedicle bone graft reconstruction of the proximal pole of the left scaphoid was done. A non-vascularized autograft from the left radius was also applied. He was put in a thumb spica cast with the interphalangeal joint free for 6 weeks. On 6-week follow-up after surgery, the patient was healing well and could make a composite fist with his left hand. The diagnosis of Preiser’s disease is primarily based on radiological findings. Due to the fact that necrosis happens over a period of time, most AVNs are diagnosed at the late stages of the disease. There appear to be no specific guidelines on the management AVN of the scaphoid. In the past, immobilization and arthroscopic debridement had been used. Radial osteotomy has also been tried. Vascularized bone grafts have also been used to treat Preiser’s disease. In our patient, we used three of these treatment modalities, starting with conservative management with topical NSAIDS and immobilization, then debridement with vascularized bone grafts.

Keywords: wrist pain, avascular necrosis of the scaphoid, Preiser’s disease, vascularized bone grafts

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Authors: George R. Puno, Eric N. Bruno

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The natural landscape of the Philippine archipelago plus the current realities of climate change make the country vulnerable to flood hazards. Flooding becomes the recurring natural disaster in the country resulting to lose of lives and properties. Musimusi is among the rivers which exhibited inundation particularly at the inhabited floodplain portion of its watershed. During the event, rescue operations and distribution of relief goods become a problem due to lack of high resolution flood maps to aid local government unit identify the most affected areas. In the attempt of minimizing impact of flooding, hydrologic modelling with high resolution mapping is becoming more challenging and important. This study focused on the analysis of flood extent as a function of different geomorphologic characteristics of Musimusi watershed. The methods include the delineation of morphometric parameters in the Musimusi watershed using Geographic Information System (GIS) and geometric calculations tools. Digital Terrain Model (DTM) as one of the derivatives of Light Detection and Ranging (LiDAR) technology was used to determine the extent of river inundation involving the application of Hydrologic Engineering Center-River Analysis System (HEC-RAS) and Hydrology Modelling System (HEC-HMS) models. The digital elevation model (DEM) from synthetic Aperture Radar (SAR) was used to delineate watershed boundary and river network. Datasets like mean sea level, river cross section, river stage, discharge and rainfall were also used as input parameters. Curve number (CN), vegetation, and soil properties were calibrated based on the existing condition of the site. Results showed that the drainage density value of the watershed is low which indicates that the basin is highly permeable subsoil and thick vegetative cover. The watershed’s elongation ratio value of 0.9 implies that the floodplain portion of the watershed is susceptible to flooding. The bifurcation ratio value of 2.1 indicates higher risk of flooding in localized areas of the watershed. The circularity ratio value (1.20) indicates that the basin is circular in shape, high discharge of runoff and low permeability of the subsoil condition. The heavy rainfall of 167 mm brought by Typhoon Seniang last December 29, 2014 was characterized as high intensity and long duration, with a return period of 100 years produced 316 m3s-1 outflows. Portion of the floodplain zone (1.52%) suffered inundation with 2.76 m depth at the maximum. The information generated in this study is helpful to the local disaster risk reduction management council in monitoring the affected sites for more appropriate decisions so that cost of rescue operations and relief goods distribution is minimized.

Keywords: flooding, geomorphology, mapping, watershed

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Authors: Precious Barnes, Abraham Mensah, Leonard Derkyi-Kwarteng, Benjamin Amoani, George Adjei, Ernest Adankwah, Faustina Pappoe, Kwabena Dankwah, Daniel Amoako-Sakyi, Samuel Victor Nuvor, Dorcas Obiri-Yeboah, Ewura Seidu Yahaya, Patrick Kafui Akakpo, Roland Osei Saahene

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Context: Breast cancer is a prevalent and aggressive type of cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) is a transcription factor that has been associated with tumor progression in breast cancer. However, there is a lack of published data on NF-kB in breast cancer patients in Ghana or other African countries. Research Aim: The aim of this study was to assess the prognostic significance of NF-kB (p65) expression and its association with various clinicopathological features in breast cancer patients at the Cape Coast Teaching Hospital in Ghana. Methodology: A total of 90 formalin-fixed breast cancer tissues and 15 normal breast tissues were used in this study. The expression level of NF-kB (p65) was examined using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Findings: The study found that NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High-level expression of NF-kB (p65) was more common in tumor grade 3 compared to grade 1, and Ki67 > 20 had higher expression of NF-kB (p65) compared to Ki67 ≤ 20. Triple-negative breast cancer patients had the highest overexpression of NF-kB (p65) compared to other molecular subtypes. There was no significant association between NF-kB (p65) expression and other clinicopathological parameters. Theoretical Importance: This study provides important insights into the expression of NF-kB (p65) in breast cancer patients in Ghana, particularly in relation to tumor grade and proliferation index. The findings suggest that NF-kB (p65) could serve as a potential biological marker for cancer stage, progression, prognosis and as a therapeutic target. Data Collection and Analysis Procedures: Formalin-fixed breast cancer tissues and normal breast tissues were collected and analyzed using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Question Addressed: This study addressed the question of the prognostic significance of NF-kB (p65) expression and its association with clinicopathological features in breast cancer patients in Ghana. Conclusion: This study, the first of its kind in Ghana, demonstrates that NF-kB (p65) is highly expressed among breast cancer patients at the Cape Coast Teaching Hospital, especially in triple-negative breast cancer patients. The expression of NF-kB (p65) is associated with tumor grade and proliferation index. NF-kB (p65) could potentially serve as a biological marker for cancer stage, progression, prognosis, and as a therapeutic target.

Keywords: breast cancer, Ki67, NF-kB (p65), tumor grade

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Authors: George Kassar, Phillip A. Cartwright

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Based on data collected from The Jones Learning Center (JLC), University of the Ozarks, Arkansas, U.S., this study explores the impact of inclusive classroom practices on neuro-diverse college students’ and their consequent academic performance having participated in integrative therapies designed to support students who are intellectually capable of obtaining a college degree, but who require support for learning challenges owing to disabilities, AD/HD, or ASD. The purpose of this study is two-fold. The first objective is to explore the general process, special techniques, and practices of the (JLC) inclusive program. The second objective is to identify and analyze the effectiveness of the processes, techniques, and practices in supporting the academic performance of enrolled college students with learning disabilities following integration into mainstream university learning. Integrity, transparency, and confidentiality are vital in the research. All questions were shared in advance and confirmed by the concerned management at the JLC. While administering the questionnaire as well as conducted the interviews, the purpose of the study, its scope, aims, and objectives were clearly explained to all participants prior starting the questionnaire / interview. Confidentiality of all participants assured and guaranteed by using encrypted identification of individuals, thus limiting access to data to only the researcher, and storing data in a secure location. Respondents were also informed that their participation in this research is voluntary, and they may withdraw from it at any time prior to submission if they wish. Ethical consent was obtained from the participants before proceeding with videorecording of the interviews. This research uses a mixed methods approach. The research design involves collecting, analyzing, and “mixing” quantitative and qualitative methods and data to enable a research inquiry. The research process is organized based on a five-pillar approach. The first three pillars are focused on testing the first hypothesis (H1) directed toward determining the extent to the academic performance of JLC students did improve after involvement with comprehensive JLC special program. The other two pillars relate to the second hypothesis (H2), which is directed toward determining the extent to which collective and applied knowledge at JLC is distinctive from typical practices in the field. The data collected for research were obtained from three sources: 1) a set of secondary data in the form of Grade Point Average (GPA) received from the registrar, 2) a set of primary data collected throughout structured questionnaire administered to students and alumni at JLC, and 3) another set of primary data collected throughout interviews conducted with staff and educators at JLC. The significance of this study is two folds. First, it validates the effectiveness of the special program at JLC for college-level students who learn differently. Second, it identifies the distinctiveness of the mix of techniques, methods, and practices, including the special individualized and personalized one-on-one approach at JLC.

Keywords: education, neuro-diverse students, program effectiveness, Jones learning center

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Authors: Panagiotis Lemonakis, Nikolaos Moisiadis, Andromachi Gkoutzini, George Kaliabetsos, Nikos Eliou

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The proper surface water drainage not only affects vehicle movement dynamics but also increases the likelihood of an accident due to the fact that inadequate drainage is associated with potential hydroplaning and splash and spray driving conditions. Nine solutions have been proposed to address hydroplaning in sections with inadequate drainage, e.g., augmented superelevation and longitudinal rates, reduction of runoff length, and skew superelevation. The latter has been extensively implemented in highways recently, enhancing the safety level in the applied road segments in regards to the effective drainage of the rainwater. However, the concept of the skew superelevation has raised concerns regarding the driver’s comfort when traveling over skew superelevation sections, particularly at high speeds. These concerns alleviated through the concept of the round-up skew superelevation, which reduces both the lateral and the vertical acceleration imposed to the drivers and hence, improves comfort and traffic safety. Various research studies aimed at investigating driving comfort by evaluating the lateral and vertical accelerations sustained by the road users and vehicles. These studies focused on the influence of the skew superelevation to passenger cars, buses and trucks, and the drivers themselves, traveling at a certain range of speeds either below or above the design speed. The outcome of these investigations which based on the use of simulations, revealed that the imposed accelerations did not exceed the statutory thresholds even when the travelling speed was significantly greater than the design speed. Nevertheless, the effect of the skew superelevation to other vehicle types for instance, motorcycles, has not been investigated so far. The present research study aims to bridge this gap by investigating the impact of skew superelevation on the motorcycle rider’s comfort. Power two-wheeler riders are susceptible to any changes on the pavement surface and therefore a comparison between the traditional superelevation practice and the skew superelevation concept is of paramount importance. The methodology based on the utilization of sophisticated software in order to design the model of the road for several values of the longitudinal slope. Based on the values of the slopes and the use of a mathematical equation, the accelerations imposed on the wheel of the motorcycle were calculated. Due to the fact that the final aim of the study is the influence of the skew superelevation to the rider, it was deemed necessary to convey the calculated accelerations from the wheel to the rider. That was accomplished by implementing the quarter car suspension model adjusted to the features of two-wheeler vehicles. Finally, the accelerations derived from this process evaluated according to specific thresholds originated from the International Organization for Standardization, which correspond to certain levels of comfort. The most important conclusion drawn is that the comfort of the riders is not dependent on the form of road gradient to a great extent due to the fact that the vertical acceleration imposed to the riders took similar values regardless of the value of the longitudinal slope.

Keywords: acceleration, comfort, motorcycle, safety, skew superelevation

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Authors: Weijing Zhou, Yuting Lei, Francis Nolan

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In the domain of second language acquisition, whenever pronunciation errors or acquisition difficulties are found, researchers habitually attribute them to the negative transfer of the native language or local dialect. To what extent do Mandarin and local dialects affect English phonological acquisition for Chinese learners of English as a foreign language (EFL)? Little evidence, however, has been found via empirical research in China. To address this core issue, the present study conducted phonetic experiments to explore the roles of local dialects and Mandarin in Chinese EFL learners’ acquisition of L2 English consonants. Besides Mandarin, the sole national language in China, Suzhou dialect was selected as the target local dialect because of its distinct phonology from Mandarin. The experimental group consisted of 30 junior English majors at Yangzhou University, who were born and lived in Suzhou, acquired Suzhou Dialect since their early childhood, and were able to communicate freely and fluently with each other in Suzhou Dialect, Mandarin as well as English. The consonantal target segments were all the consonants of English, Mandarin and Suzhou Dialect in typical carrier words embedded in the carrier sentence Say again. The control group consisted of two Suzhou Dialect experts, two Mandarin radio broadcasters, and two British RP phoneticians, who served as the standard speakers of the three languages. The reading corpus was recorded and sampled in the phonetic laboratories at Yangzhou University, Soochow University and Cambridge University, respectively, then transcribed, segmented and analyzed acoustically via Praat software, and finally analyzed statistically via EXCEL and SPSS software. The main findings are as follows: First, in terms of correct acquisition rates (CARs) of all the consonants, Mandarin ranked top (92.83%), English second (74.81%) and Suzhou Dialect last (70.35%), and significant differences were found only between the CARs of Mandarin and English and between the CARs of Mandarin and Suzhou Dialect, demonstrating Mandarin was overwhelmingly more robust than English or Suzhou Dialect in subjects’ multilingual phonological ecology. Second, in terms of typical acoustic features, the average duration of all the consonants plus the voice onset time (VOT) of plosives, fricatives, and affricatives in 3 languages were much longer than those of standard speakers; the intensities of English fricatives and affricatives were higher than RP speakers but lower than Mandarin and Suzhou Dialect standard speakers; the formants of English nasals and approximants were significantly different from those of Mandarin and Suzhou Dialects, illustrating the inconsistent acoustic variations between the 3 languages. Thirdly, in terms of typical pronunciation variations or errors, there were significant interlingual interactions between the 3 consonant systems, in which Mandarin consonants were absolutely dominant, accounting for the strong transfer from L1 Mandarin to L2 English instead of from earlier-acquired L1 local dialect to L2 English. This is largely because the subjects were knowingly exposed to Mandarin since their nursery and were strictly required to speak in Mandarin through all the formal education periods from primary school to university.

Keywords: acquisition of L2 English consonants, role of Mandarin, role of local dialect, Chinese EFL learners from Suzhou Dialect areas

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Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

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The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

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Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Amanda M. McLeroy, Tiera Tanksley

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The 2020 movement for Black Lives, ignited by anti-Black police brutality and exemplified by the public execution of George Floyd, underscored the dual potential of social media for political activism and perilous exposure to traumatic content for Black students. This study employs Critical Race Technology Theory (CRTT) to scrutinize algorithmic anti-blackness and its impact on Black youth's lives and educational experiences. The research investigates the consequences of vicarious exposure to police brutality on social media among Black adolescents through qualitative interviews and quantitative scale data. The findings reveal an unprecedented surge in exposure to viral police killings since 2020, resulting in profound physical, socioemotional, and educational effects on Black youth. CRTT forms the theoretical basis, challenging the notion of digital technologies as post-racial and neutral, aiming to dismantle systemic biases within digital systems. Black youth, averaging over 13 hours of daily social media use, face constant exposure to graphic images of Black individuals dying. The study connects this exposure to a range of physical, socioemotional, and mental health consequences, emphasizing the urgent need for understanding and support. The research proposes questions to explore the extent of police brutality exposure and its effects on Black youth. Qualitative interviews with high school and college students and quantitative scale data from undergraduates contribute to a nuanced understanding of the impact of police brutality exposure on Black youth. Themes of unprecedented exposure to viral police killings, physical and socioemotional effects, and educational consequences emerge from the analysis. The study uncovers how vicarious experiences of negative police encounters via social media lead to mistrust, fear, and psychosomatic symptoms among Black adolescents. Implications for educators and counselors are profound, emphasizing the cultivation of empathy, provision of mental health support, integration of media literacy education, and encouragement of activism. Recognizing family and community influences is crucial for comprehensive support. Professional development opportunities in culturally responsive teaching and trauma-informed approaches are recommended for educators. In conclusion, creating a supportive educational environment that addresses the emotional impact of social media exposure to police brutality is crucial for the well-being and development of Black adolescents. Counselors, through safe spaces and collaboration, play a vital role in supporting Black youth facing the distressing effects of social media exposure to police brutality.

Keywords: black youth, mental health, police brutality, social media

Procedia PDF Downloads 26

Authors: Henry Nicholas Lee, George Thomas, Juliana Johari, Carmilla Freddie, Caroline Val Madin

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Research in comparative and international education often provides value-laden views of an education system within and in between other countries. These views are frequently used by policy makers or educators to explore similarities and differences for, among others, benchmarking purposes. In this study, a comparison is made between Malaysia and England, focusing on the process of writing children went through to create a text, using a multimodal theoretical framework to analyse this comparison. The main purpose is political in nature as it served as an answer to Malaysia’s call for benchmarking of best practices for language learning. Furthermore, the focus on writing in this study adds into more empirical findings about early writers’ writing development and writing improvement, especially for children at the ages of 5-9. In research, comparative studies in English as a Second Language (ESL) writing pedagogy – particularly in Malaysia since the introduction of the Standard- based English Language Curriculum (KSSR) in 2011 as a draft and its full implementation in 2017; reviewed 2018 KSSR-CEFR aligned – has not been done comparatively. In theory, a multimodal theoretical framework somehow allows a logical comparison between first language and ESL which would provide useful insights to illuminate the writing process between Malaysia and England. The comparisons are not representative because of the different school systems in both countries. So far, the literature informs us that the curriculum for language learning is very much emphasised on children’s linguistic abilities, which include their proficiency and mastery of the language, its conventions, and technicalities. However, recent empirical findings suggested that literacy in its concepts and characters need change. In view of this suggestion, the comparison will look at how the process of writing is implemented through the five modes of communication: linguistic, visual, aural, spatial, and gestural. This project draws on data from Malaysia and England, involving 10 teachers, 26 classroom observations, 20 lesson plans, 20 interviews, and 20 brief conversations with teachers. The research focused upon 20 primary children of different genders aged 5-9, and in addition to primary data descriptions, 40 children’s works, 40 brief classroom conversations, 30 classroom photographs, and 30 school compound photographs were undertaken to investigate teachers and children’s use of modes and semiotic resources to design a text. The data were analysed by means of within-case analysis, cross-case analysis, and constant comparative analysis, with an initial stage of data categorisation, followed by general and specific coding, which clustered the data into thematic groups. The study highlights the importance of teachers’ and children’s engagement and interaction with various modes of communication, an adaptation from the English approaches to teaching writing within the KSSR framework and providing ‘voice’ to ESL writers to ensure that both have access to the knowledge and skills required to make decisions in developing multimodal texts and artefacts.

Keywords: comparative education, early writers, KSSR, multimodal theoretical framework, writing development

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Authors: Sachil Kumar, Anoop Kumar Verma, Wahid Ali, Uma Shankar Singh

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Globally approximately 55.3 million people die each year. In the India there were 95 lakh annual deaths in 2013. The number of deaths resulted from homicides, suicides and unintentional injuries in the same period was about 5.7 lakh. The ever-increasing crime rate necessitated the development of methods for determining time since death. An erroneous time of death window can lead investigators down the wrong path or possibly focus a case on an innocent suspect. In this regard a research was carried out by analyzing the temperature dependent degradation of a Cardiac Troponin-T protein (cTnT) in the myocardium postmortem as a marker for time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (in the Department of Forensic Medicine and Toxicology, King George’s Medical University, Lucknow India) after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC), 12 0C, 25 0C and 37 0C for different time periods ((~5, 26, 50, 84, 132, 157, 180, 205, and 230 hours). The cases included were the subjects of road traffic accidents (RTA) without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. The data shows a distinct temporal profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. The disappearance of intact cTnT and the appearance of lower molecular weight bands are easily observed. Western blot data clearly showed the intact protein at 42 kDa, two major (27 kDa, 10kDa) fragments, two additional minor fragments (32 kDa) and formation of low molecular weight fragments as time increases. At 12 0C the intensity of band (intact cTnT) decreased steadily as compared to RT, 25 0C and 37 0C. Overall, both PMI and temperature had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 38 h and at the highest temperature, 37 0C. The combination of high temperature (37 0C) and long Postmortem interval (105.15 hrs) had the most drastic effect on the breakdown of cTnT. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the log of the time postmortem. These plots show a good coefficient of correlation of r = 0.95 (p=0.003) for the regression of the human heart at different temperature conditions. The data presented demonstrates that this technique can provide an extended time range during which Postmortem interval can be more accurately estimated.

Keywords: degradation, postmortem interval, proteolysis, temperature, troponin

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Authors: Stavros T. Ponis, George D. Plakas-Koumadorakis, Sotiris P. Gayialis

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Augmented Reality (AR) can be defined as a technology, which takes the capabilities of computer-generated display, sound, text and effects to enhance the user's real-world experience by overlaying virtual objects into the real world. By doing that, AR is capable of providing a vast array of work support tools, which can significantly increase employee productivity, enhance existing job training programs by making them more realistic and in some cases introduce completely new forms of work and task executions. One of the most promising AR industrial applications, as literature shows, is the use of Head Worn, monocular or binocular Displays (HWD) to support logistics and production operations, such as order picking, part assembly and maintenance. This paper presents the initial results of an ongoing research project for the introduction of a dedicated AR-HWD solution to the picking process of a Distribution Center (DC) in Greece operated by a large Telecommunication Service Provider (TSP). In that context, the proposed research aims to determine whether gamification elements should be integrated in the functional requirements of the AR solution, such as providing points for reaching objectives and creating leaderboards and awards (e.g. badges) for general achievements. Up to now, there is a an ambiguity on the impact of gamification in logistics operations since gamification literature mostly focuses on non-industrial organizational contexts such as education and customer/citizen facing applications, such as tourism and health. To the contrary, the gamification efforts described in this study focus in one of the most labor- intensive and workflow dependent logistics processes, i.e. Customer Order Picking (COP). Although introducing AR in COP, undoubtedly, creates significant opportunities for workload reduction and increased process performance the added value of gamification is far from certain. This paper aims to provide insights on the suitability and usefulness of AR-enhanced gamification in the hard and very demanding environment of a logistics center. In doing so, it will utilize a review of the current state-of-the art regarding gamification of production and logistics processes coupled with the results of questionnaire guided interviews with industry experts, i.e. logisticians, warehouse workers (pickers) and AR software developers. The findings of the proposed research aim to contribute towards a better understanding of AR-enhanced gamification, the organizational change it entails and the consequences it potentially has for all implicated entities in the often highly standardized and structured work required in the logistics setting. The interpretation of these findings will support the decision of logisticians regarding the introduction of gamification in their logistics processes by providing them useful insights and guidelines originating from a real life case study of a large DC operating more than 300 retail outlets in Greece.

Keywords: augmented reality, technology acceptance, warehouse management, vision picking, new forms of work, gamification

Procedia PDF Downloads 117

Authors: Claudia P. Saunderson

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Widening of participation in higher education globally has increased diversity of student populations. However, widening participation is more than mere access. Central to the debate about widening participation are social justice issues of authentic inclusion and appropriate support for success for all students in higher education (HE). Given the recent global campaign for 'Black Lives Matter' as well as the worldwide advocacy for justice in the George Floyd case, the importance of the experiences of Black men, were again poignantly foregrounded. The literature abounds with the negative experiences of Black male students in higher education. Much of this literature emanates from the Global North, with little systematic research on black male students' university experiences originating from the Global South. This research, therefore, explores the psychosocial experiences of Black male students at a historically white South African university. Not only are these students' educational or academic adjustment important, but so is their psychosocial adjustment to the institution. The psychosocial adjustment might include emotional well-being, motivation, as well as the student’s perception of how well he fits in or is made to feel welcome at the institution. The study draws on strands of critical race theory (CRT), co-cultural theory (CCT) as well as defining properties of micro-aggression theory (MAT). In the study, CRT, therefore, served as an overarching theory at the macro level, and it comments on the structural dynamics while MAT and CCT rather focussed on the impact of structural arrangements like racialization, at an individual and micro-level. These theories furthermore provided a coherent analytic framework for this study. Using a case study design, this qualitative study, employing focus groups and individual interviews, drew on the psychosocial experiences of twenty Black male students to explore how they navigate this specific historically white campus. The data were analyzed using thematic analysis that provided a systematic procedure for generating codes and themes from the qualitative data. The study found that the combination of race and gender-based micro-aggressions experienced by students included negative stereotyping, criminalization as well as racial profiling and that these experiences impede participants' ability to thrive at the institution. However, participants also shared positive perspectives about the institution. Some of the positive traits of the institution that the participants mentioned were well-aligned administration, good quality of education, as well as various funding opportunities. This study implies that if any HE institution values transformation, it necessitates the exploration and interrogation of potential aspects that are subtly hidden in the institutional culture and environment that might serve as barriers to the transformation process. This positioning is based on a social justice stance and believes that all students are equal and have the right to racially and culturally equitable and appropriate education and support.

Keywords: critical race theory, higher education transformation, micro-aggression, student experience

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Authors: Adil Murtaza, Muhammad Tahir Khan, Awais Ghani, Chao Zhou, Sen Yang, Xiaoping Song

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The morphotropic phase boundary (MPB); a boundary between two different crystallographic symmetries in the composition–temperature phase diagram has been widely studied in ferroelectrics and recently has drawn interest in ferromagnets for obtaining enhanced large field-induced strain. At MPB, the system gets a compressed free energy state, which allows the polarization to freely rotate and hence results in a high magnetoelastic response (e.g., high magnetization, low coercivity, and large magnetostriction). Based on the same mechanism, we designed MPB in a ferromagnetic Tb₁₋ₓNdₓCo₂ system. The temperature-dependent magnetization curves showed spin reorientation (SR); which can be explained by a two-sublattice model. Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb₀.₃₅Nd₀.₆₅Co₂ exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The coercive field (HC) under a low magnetic field and first anisotropy constant (K₁) shows a minimum value at MPB composition of x=0.65. A detailed spin configuration diagram is provided for the Tb₁₋ₓNdₓCo₂ around the composition for the anisotropy compensation; this can guide the development of novel magnetostrictive materials. The anisotropic magnetostriction (λS) first decreased until x=0.8 and then continuously increased in the negative direction with further increase of Nd concentration. In addition, the large ratio between magnetostriction and the absolute values of the first anisotropy constant (λS/K₁) appears at MPB, indicating that Tb₀.₃₅Nd₀.₆₅Co₂ has good magnetostrictive properties. Present work shows an anomalous type of MPB in ferromagnetic materials, revealing that MPB can also lead to a weakening of magnetoelastic behavior as shown in the ferromagnetic Tb₁₋ₓNdₓCo₂ system. Our work shows the universal presence of MPB in ferromagnetic materials and suggests the differences between different ferromagnetic MPB systems that are important for substantial improvement of magnetic and magnetostrictive properties. Based on the results of this study, similar MPB effects might be achieved in other ferroic systems that can be used for technological applications. The finding of magnetic MPB in the ferromagnetic system leads to some important significances. First, it provides a better understanding of the fundamental concept of spin reorientation transitions (SRT) like ferro-ferro transitions are not only reorientation of magnetization but also crystal symmetry change upon magnetic ordering. Second, the flattened free energy corresponding to a low energy barrier for magnetization rotation and enhanced magnetoelastic response near MPB. Third, to attain large magnetostriction with MPB approach two terminal compounds have different easy magnetization directions below Curie temperature Tc in order to accomplish the weakening of magnetization anisotropy at MPB (as in ferroelectrics), thus easing the magnetic domain switching and the lattice distortion difference between two terminal compounds should be large enough, e.g., lattice distortion of R symmetry ˃˃ lattice distortion of T symmetry). So that the MPB composition agrees to a nearly isotropic state along with large ‘net’ lattice distortion, which is revealed in a higher value of magnetostriction.

Keywords: magnetization, magnetostriction, morphotropic phase boundary (MPB), phase transition

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Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

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Authors: Stephanie Wall, Guido Wimmers

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The construction and operation of buildings greatly contribute to environmental degradation through resource and energy consumption and greenhouse gas emissions. The design of the envelope system affects the environmental impact of a building in two major ways; 1) high thermal performance and air tightness can significantly reduce the operational energy of the building and 2) the material selection for the envelope largely impacts the embodied energy of the building. Life cycle assessment (LCA) is a scientific methodology that is used to systematically analyze the environmental load of processes or products, such as buildings, over their life. The paper will discuss the results of a comparative LCA of different envelope designs and the long-term monitoring of the Wood Innovation Research Lab (WIRL); a Passive House (PH), industrial building under construction in Prince George, Canada. The WIRL has a footprint of 30m x 30m on a concrete raft slab foundation and consists of shop space as well as a portion of the building that includes a two-story office/classroom space. The lab building goes beyond what was previously thought possible in regards to energy efficiency of industrial buildings in cold climates due to their large volume to surface ratio, small floor area, and high air change rate, and will be the first PH certified industrial building in Canada. These challenges were mitigated through the envelope design which utilizes solar gains while minimizing overheating, reduces thermal bridges with thick (570mm) prefabricated truss walls filled with blown in mineral wool insulation and a concrete slab and roof insulated with EPS rigid insulation. The envelope design results in lower operational and embodied energy when compared to buildings built to local codes or with steel. The LCA conducted using Athena Impact Estimator for Buildings identifies project specific hot spots as well illustrates that for high-efficiency buildings where the operational energy is relatively low; the embodied energy of the material selection becomes a significant design decision as it greatly impacts the overall environmental footprint of the building. The results of the LCA will be reinforced by long-term monitoring of the buildings envelope performance through the installation of temperature and humidity sensors throughout the floor slab, wall and roof panels and through detailed metering of the energy consumption. The data collected from the sensors will also be used to reinforce the results of hygrothermal analysis using WUFI®, a program used to verify the durability of the wall and roof panels. The WIRL provides an opportunity to showcase the use of wood in a high performance envelope of an industrial building and to emphasize the importance of considering the embodied energy of a material in the early stages of design. The results of the LCA will be of interest to leading researchers and scientists committed to finding sustainable solutions for new construction and high-performance buildings.

Keywords: high performance envelope, life cycle assessment, long term monitoring, passive house, prefabricated panels

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Authors: Maria Fatima Almeida, Rodrigo Calili, George Soares, João Krause, Myrthes Marcele Dos Santos, Anna Carolina Suzano E. Silva, Marcos Alexandre Da

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In Brazil, the building sector accounts for 1/6 of energy consumption and 50% of electricity consumption. A complex sector with several driving actors plays an essential role in the country's economy. Currently, the digitalization readiness in this sector is still low, mainly due to the high investment costs and the difficulty of estimating the benefits of digital technologies in buildings. Nevertheless, the potential contribution of digitalization for increasing energy efficiency in the building sector in Brazil has been pointed out as relevant in the political and sectoral contexts, both in the medium and long-term horizons. To contribute to the debate on the possible evolving trajectories of digitalization in the building sector in Brazil and to subsidize the formulation or revision of current public policies and managerial decisions, three future scenarios were created to anticipate the potential energy efficiency in the building sector in Brazil due to digitalization by 2050. This work aims to present these scenarios as a basis to foresight the potential energy efficiency in this sector, according to different digitalization paces - slow, moderate, or fast in the 2050 horizon. A methodological approach was proposed to create alternative prospective scenarios, combining the Global Business Network (GBN) and the Laboratory for Investigation in Prospective Strategy and Organisation (LIPSOR) methods. This approach consists of seven steps: (i) definition of the question to be foresighted and time horizon to be considered (2050); (ii) definition and classification of a set of key variables, using the prospective structural analysis; (iii) identification of the main actors with an active role in the digital and energy spheres; (iv) characterization of the current situation (2021) and identification of main uncertainties that were considered critical in the development of alternative future scenarios; (v) scanning possible futures using morphological analysis; (vi) selection and description of the most likely scenarios; (vii) foresighting the potential energy efficiency in each of the three scenarios, namely slow digitalization; moderate digitalization, and fast digitalization. Each scenario begins with a core logic and then encompasses potentially related elements, including potential energy efficiency. Then, the first scenario refers to digitalization at a slow pace, with induction by the government limited to public buildings. In the second scenario, digitalization is implemented at a moderate pace, induced by the government in public, commercial, and service buildings, through regulation integrating digitalization and energy efficiency mechanisms. Finally, in the third scenario, digitalization in the building sector is implemented at a fast pace in the country and is strongly induced by the government, but with broad participation of private investments and accelerated adoption of digital technologies. As a result of the slow pace of digitalization in the sector, the potential for energy efficiency stands at levels below 10% of the total of 161TWh by 2050. In the moderate digitalization scenario, the potential reaches 20 to 30% of the total 161TWh by 2050. Furthermore, in the rapid digitalization scenario, it will reach 30 to 40% of the total 161TWh by 2050.

Keywords: building digitalization, energy efficiency, scenario building, prospective structural analysis, morphological analysis

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Weixiao Wei, Chris Shei

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This paper describes Mandate of Heaven as a source of justification for the ruling regime from ancient China approximately three thousand years ago. Initially, the kings of Shang dynasty simply nominated themselves as the sons of Heaven sent to Earth to rule the common people. As the last generation of the kings became corrupted and ruled withbrutal force and crueltywhich directly caused their destruction, the successive kings of Zhou dynasty realised the importance of virtue and the provision of goods to the people. Legitimacy of the ruling regimes became rested not entirely on random allocation of the throne by an unknown supernatural force but on a foundation comprising morality and the ability to provide goods. The latter composite was picked up by the current ruling regime, the Chinese Communist Party, and became the cornerstone of its political legitimacy, also known as ‘performance legitimacy’ where economic development accounts for the satisfaction of the people in place of election and other democratic means of providing legal-rational legitimacy. Under this circumstance, it becomes important as well for the ruling party to use political rhetoric to convince people of the good performance of the government in the economy, morality, and foreign policy. Thus, we see a lot of propaganda materials in both government policy statements and international press conference announcements. The former consists mainly of important speeches made by prominent figures in Party conferences which are not only made publicly available on the government websites but also become obligatory reading materials for university entrance examinations. The later consists of announcements about foreign policies and strategies and actions taken by the government regarding foreign affairsmade in international conferences and offered in Chinese-English bilingual versions on official websites. This documentation strategy creates an impressive image of the Chinese Communist Party that is domestically competent and international strong, taking care of the people it governs in terms of economic needs and defending the country against any foreign interference and global adversities. This political discourse system comprising reading materials fully extractable from government websites also becomes excellent repertoire for teaching and researching in contemporary Chinese language, discourse and rhetoric, Chinese culture and tradition, Chinese political ideology, and Chinese-English translation. This paper aims to provide a detailed and comprehensive description of the current Chinese political discourse system, arguing about its lineage from the rhetorical convention of Mandate of Heaven in ancient China and its current concentration on serving the people in place of election, human rights, and freedom of speech. The paper will also provide guidelines as to how this discourse system and the manifestation of official documents created under this system can become excellent research and teaching materials in applied linguistics.

Keywords: mandate of heaven, Chinese communist party, performance legitimacy, serving the people, political discourse

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Authors: Albert Mufundirwa, Satoru Yoshioka, K. Ogi, Takeharu Sugiyama, George F. Harrington, Bretislav Smid, Benjamin Cunning, Kazunari Sasaki, Akari Hayashi, Stephen M. Lyth

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Polymer electrolyte membrane fuel cells (PEMFCs) are electrochemical energy conversion devices used for portable, residential and vehicular applications due to their low emissions, high efficiency, and quick start-up characteristics. However, PEMFCs generally use expensive, Pt-based electrocatalysts as electrode catalysts. Due to the high cost and limited availability of platinum, research and development to either drastically reduce platinum loading, or replace platinum with alternative catalysts is of paramount importance. A combination of high surface area supports and nano-structured active sites is essential for effective operation of catalysts. We synthesize carbon foam supports by thermal decomposition of sodium ethoxide, using a template-free, gram scale, cheap, and scalable pyrolysis method. This carbon foam has a high surface area, highly porous, three-dimensional framework which is ideal for electrochemical applications. These carbon foams can have surface area larger than 2500 m²/g, and electron microscopy reveals that they have micron-scale cells, separated by few-layer graphene-like carbon walls. We applied this carbon foam as a platinum catalyst support, resulting in the improved electrochemical surface area and mass activity for the oxygen reduction reaction (ORR), compared to carbon black. Similarly, silver-decorated carbon foams showed higher activity and efficiency for electrochemical carbon dioxide conversion than silver-decorated carbon black. A promising alternative to Pt-catalysts for the ORR is iron-impregnated nitrogen-doped carbon catalysts (Fe-N-C). Doping carbon with nitrogen alters the chemical structure and modulates the electronic properties, allowing a degree of control over the catalytic properties. We have adapted our synthesis method to produce nitrogen-doped carbon foams with large surface area, using triethanolamine as a nitrogen feedstock, in a novel bottom-up protocol. These foams are then infiltrated with iron acetate (FeAc) and pyrolysed to form Fe-N-C foams. The resulting Fe-N-C foam catalysts have high initial activity (half-wave potential of 0.68 VRHE), comparable to that of commercially available Pt-free catalysts (e.g., NPC-2000, Pajarito Powder) in acid solution. In alkaline solution, the Fe-N-C carbon foam catalysts have a half-wave potential of 0.89 VRHE, which is higher than that of NPC-2000 by almost 10 mVRHE, and far out-performing platinum. However, the durability is still a problem at present. The lessons learned from X-ray absorption spectroscopy (XAS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and electrochemical measurements will be used to carefully design Fe-N-C catalysts for higher performance PEMFCs.

Keywords: carbon-foam, polymer electrolyte membrane fuel cells, platinum, Pt-free, Fe-N-C, ORR

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Authors: Maria de Fátima Lambert

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Following previous studies about Writing and Seeing, this paper focuses on the aesthetic assumptions within the concept of Winter Journey (Voyage d’Hiver/Winterreise) both in Georges Perec’s Saga and the Oulipo Group vis-à-vis with the creations by William Kentridge and Michael Borremans. The aesthetic and artistic connections are widespread. Nevertheless, we can identify common poetical principles shared by these different authors, not only according to the notion of ekphrasis, but also following the procedures of contemporary creation in literature and visual arts. The analysis of the ongoing process of the French writers as individuals and as group and the visual artists’ acting might contribute for another crossed definition of contemporary conception. The same title/theme was a challenge and a goal for them. Let’s wonder how deep the concept encouraged them and which symbolic upbringings were directing their poetical achievements. The idea of an inner journey became the main point, and got “over” and “across” a shared path worth to be followed. The authors were chosen due to the resilient contents of their visual and written images, and looking for the reasons that might had driven their conceptual basis to be. In Pérec’s “Winter Journey” as for the following fictions by Jacques Roubaud, Hervé le Tellier, Jacques Jouet and Hugo Vernier (that emerges from Perec’s fiction and becomes a real author) powerful aesthetic and enigmatic reflections grow connected with a poetic (and aesthetic) understanding of Walkscapes. They might be assumed as ironic fictions and poetical drifts. Outstanding from different logics, the overwhelming impact of Winterreise Lied by Schubert after Wilhelm Müller’s poems is a major reference in present authorship creations. Both Perec and Oulipo’s author’s texts are powerfully ekphrastic, although we should not forget they follow goals, frameworks and identities. When acting as a reader, they induce powerful imageries - cinematic or cinematographic - that flow in our minds. It was well-matched with William Kentridge animated video Winter Journey (2014) and the creations (sharing the same title) of Michael Borremans (2014) for the KlaraFestival, Bozar, Cité de la musique, in Belgium. Both were taken by the foremost Schubert’s Winterreise. Several metaphors fulfil new Winter Journeys (or Travels) that were achieved in contemporary art and literature, as it once succeeded in the 19^th century. Maybe the contemporary authors and artists were compelled by the consciousness of nothingness, although outstanding different aesthetics and ontological sources. The unbearable knowledge of the road’s end, and also the urge of fulfilling the void might be a common element to all of them. As Schopenhauer once wrote, after all, Art is the only human subjective power that we can call upon in life. These newer aesthetic meanings, released from these winter journeys are surely open to wider approaches that might happen in other poetic makings to be.

Keywords: Aesthetic, voyage D’Hiver, George Perec & Oulipo, William Kentridge & Michael Borreman, Schubert's Winterreise

Procedia PDF Downloads 174

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

Procedia PDF Downloads 274