755 research outputs found
Generic model for measuring benefits of BIM as a learning tool in construction tasks
Over the past years, people’s understanding of building information modeling (BIM) in the architecture, engineering, and construction (AEC) industry has improved significantly. Building information modeling can be diversely recognized as a virtual design and construction environment, a communication vehicle among stakeholders, a lifelong information model, or an education platform that can be used in universities and colleges. Building information modeling can also be used as a learning tool that can aid project teams in familiarizing themselves with a construction task before commencement of the task on-site. Yet, little effort has been made to measure the benefits of this kind. The aim of this research is to empirically measure the benefits of BIM as a learning tool in real-life construction tasks. The learning curves of two situations—construction tasks with and construction tasks without BIM—are identified by following a series of analytical processes. The two learning curves are compared and the learning effects contributed by BIM are modeled as L effBIM . By inputting their own data, practitioners may use this generic model to measure learning effects contributed by BIM in their own projects. The model can be used to encourage potential BIM users by showing empirical evidence of BIM’s benefits. It is also hoped that the model can join the concerted efforts to promote BIM’s value in the AEC industry. © 2013 American Society of Civil Engineers.postprin
A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road
Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes
A review of literature on family caregivers of cancer patients in mainland China
2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe
Minimization of phonon-tunneling dissipation in mechanical resonators
Micro- and nanoscale mechanical resonators have recently emerged as
ubiquitous devices for use in advanced technological applications, for example
in mobile communications and inertial sensors, and as novel tools for
fundamental scientific endeavors. Their performance is in many cases limited by
the deleterious effects of mechanical damping. Here, we report a significant
advancement towards understanding and controlling support-induced losses in
generic mechanical resonators. We begin by introducing an efficient numerical
solver, based on the "phonon-tunneling" approach, capable of predicting the
design-limited damping of high-quality mechanical resonators. Further, through
careful device engineering, we isolate support-induced losses and perform the
first rigorous experimental test of the strong geometric dependence of this
loss mechanism. Our results are in excellent agreement with theory,
demonstrating the predictive power of our approach. In combination with recent
progress on complementary dissipation mechanisms, our phonon-tunneling solver
represents a major step towards accurate prediction of the mechanical quality
factor.Comment: 12 pages, 4 figure
Development of Measure Yourself Concerns and Wellbeing for informal caregivers of people with cancer – a multicentred study
Purpose: Measure Yourself Concerns and Wellbeing (MYCaW) is a validated person-centred measure of the concerns and wellbeing of people affected by cancer. Research suggests that the concerns of informal caregivers (ICs) are as complex and severely rated as people with cancer, yet MYCaW has only been used to represent cancer patients’ concerns and wellbeing. This paper reports on the development of a new qualitative coding framework for MYCaW to capture the concerns of ICs, to better understand the needs of this group.
Methods: This multicentred study involved collection of data from ICs receiving support from two UK cancer support charities (Penny Brohn UK and Cavendish Cancer Care). Qualitative codes were developed through a detailed thematic analysis of ICs’ stated concerns.
Results: Thematic analysis of IC questionnaire data identified key themes which were translated into a coding framework with two overarching sections; 1. ‘informal caregiver concerns for self’ and 2. ‘informal caregiver concerns for the person with cancer’. Supercategories with specific accompanying codes were developed for each section. Two further rounds of framework testing across different cohorts allowed for iterative development and refinement of the framework content.
Conclusions: This is the first person-centred tool specifically designed for capturing IC’s concerns through their own words. This coding framework will allow for IC data to be analysed using a rigorous and reproducible method, and therefore reported in a standardised way. This may also be of interest to those exploring the needs of ICs of people in other situations
Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar−/−) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, and require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans
Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor
© 2016, National Academy of Sciences. All rights reserved. The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+ transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+ transition and that the binding of CaM to IQ1 increases Ca2+ affinity and substantially changes the kinetics of the Ca2+ transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+ sensor responding to distinct calcium signals
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A multilevel intervention to promote HPV vaccination among young adults in Texas: protocol for a randomized controlled trial
BackgroundHuman papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.MethodsThe study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention.DiscussionRecruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden.Trial registrationNCT05057312
Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency
Background
Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined.
Results
We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired.
Conclusion
Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics
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