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Shalev, Moshe. "Boston proposes stringent regulations of biological laboratories." Lab Animal 35, no. 1 (January 2006): 14. http://dx.doi.org/10.1038/laban0106-14.
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Thalheimer, Erich. "Developing a Comprehensive Construction Noise Specification." INTER-NOISE and NOISE-CON Congress and Conference Proceedings 266, no. 2 (May 25, 2023): 10–17. http://dx.doi.org/10.3397/nc_2023_0003.
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As acoustical engineers, we are often asked to develop community noise-related guidelines, regulations, laws, ordinances, and project specifications. This paper will describe the ingredients needed to develop a robust and defensible construction noise specification that is both enforceable and effective. It will be based on the author's past and current experiences developing such specifications, including those used for the Big Dig project in Boston, FHWA's construction noise handbook, the New York City construction noise regulation, as well as dozens of large-scale construction projects across the country. The goals of proactive and reactive noise control and the difference between a performance-based versus a prescriptive-based specification will be explained, community noise criteria will be suggested, and examples will be provided for important clauses in such a specification. Lastly, a listing of "lessons learned" over the decades will be provided.
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Paté-Cornell, M. Elisabeth. "Costs and Benefits of Seismic Upgrading of Some Buildings in the Boston Area." Earthquake Spectra 1, no. 4 (August 1985): 721–40. http://dx.doi.org/10.1193/1.1585290.
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We examine here the costs and benefits of reinforcing some existing buildings in Boston at the time of remodelling with significant change of use. The buildings of interest are the unreinforced masonry warehouses and the reinforced concrete manufacturing buildings that are remodelled into apartment or office buildings. Given some estimates of the Boston seismicity and of the performance of these buildings in earthquakes with and without additional reinforcement, we evaluate three possible levels of reinforcement that the Masssachusetts Seismic Advisory Committee could recommend as part of the building codes. For the unreinforced masonry buildings, the first upgrading level is the addition of floor and roof diaphragms, and the two subsequent levels involve addition of internal walls and reinforcement of the existing ones. For the reinforced concrete buildings, the first level involves increase of the shear walls' size, and higher upgrading levels involve addition of shear walls and increase of the columns' size. We introduce in our study the market effects of the additional costs. We conclude that only the first levels of reinforcement that we considered could be adopted as regulations, and that higher standards should be left to the choice of the buildings' occupants.
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Weinstein, Asha. "Curing Congestion: Competing Plans for a Loop Highway and Parking Regulations in Boston in the 1920s." Journal of Planning History 3, no. 4 (November 2004): 292–311. http://dx.doi.org/10.1177/1538513204269598.
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Aryani, Rosalia Nita, Ni Made Rustini, and Taman Sari. "Analisis Posisi Bersaing dan Strategi Bauran Pemasaran untuk Meningkatkan Jumlah Kunjungan Pada Handara Golf and Resort di Bedugul Bali." WACANA EKONOMI (Jurnal Ekonomi, Bisnis dan Akuntansi) 19, no. 2 (September 23, 2020): 91–97. http://dx.doi.org/10.22225/we.19.2.2318.91-97.
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This research to determine the competitive position based on the Boston Consulting Group matrix, to find out internal variables including strengths and weaknesses as well as external variables including opportunities and threats and to find out relevant marketing mix strategies to increase the number of visits. The study was conducted at Handara Golf and Resort in Bedugul Bali. Data analysis techniques used are the Boston Consulting Group matrix analysis and SWOT analysis. The analysis shows that using BCG matrix analysis, the company is in the position of dogs with a growth rate of 7.09% and an analysis of market share of 0.17. Using a SWOT analysis shows that the most dominant external opportunity variable with the acquisition of 3.80 results. Where the opportunity indicator is an increase in the number of tourists, growth in online sales, buyers want more images in electronic commerce or e-commerce when buying a product, most of the time on mobile devices is used, social media plays a major role in the distribution of most of the time used on mobile devices, technological advances over the use of social media, per capita income growing in Indonesia, located in the Pacific Ring of Fire, new regulations from Bank Indonesia. While the threat indicator is providing alternative tourist attractions throughout Indonesia to tourists other than in Bali and losing followers in the social media, it can be concluded that companies need to implement a turn-around strategy because external opportunities are more oriented to supporting the company's Handara Golf and Resort Bali.
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Su, Haiyan, and Linlin Chen. "Empirical-Likelihood-Based Inference for Partially Linear Models." Mathematics 12, no. 1 (January 4, 2024): 162. http://dx.doi.org/10.3390/math12010162.
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Partially linear models find extensive application in biometrics, econometrics, social sciences, and various other fields due to their versatility in accommodating both parametric and nonparametric elements. This study aims to establish statistical inference for the parametric component effects within these models, employing a nonparametric empirical likelihood approach. The proposed method involves a projection step to eliminate the nuisance nonparametric component and utilizes an empirical-likelihood-based technique, along with the Bartlett correction, to enhance the coverage probability of the confidence interval for the parameter of interest. This method demonstrates robustness in handling normally and non-normally distributed errors. The proposed empirical likelihood ratio statistic converges to a limiting chi-square distribution under certain regulations. Simulation studies demonstrate that this method provides better inference in terms of coverage probabilities compared to the conventional normal-approximation-based method. The proposed method is illustrated by analyzing the Boston housing data from a real study.
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Williams, Joyce, and David Williams. "How the Deadliest Nightclub Fire in History Improved Medical Interventions and Regulations and Impacted Legal Enforcement." Prehospital and Disaster Medicine 38, S1 (May 2023): s82. http://dx.doi.org/10.1017/s1049023x23002352.
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Introduction:This presentation is a continuation of a WADEM presentation from 2013 entitled: Fires in Social Settings: An Examination of Prevention Strategies.Method:Nightclubs should be a place of fun and frivolity, but sometimes they become a place of death and destruction. The fire at the Cocoanut Grove in Boston Massachusetts, USA, in November, 1942 was the deadliest nightclub fire worldwide with a death toll of 492 and over 130 injured. Since that tragedy, regulations that could prevent or mitigate lethal incidents at nightclubs continue to be unenforced globally. This presentation will describe not only elements leading up to the Cocoanut Grove fire, but the resulting advances that have improved the lives and safety of the public.Results:The discussion begins by examining the general environment within the U.S. in fall of 1942. Appointed and elected officials tasked with protecting the public to reduce occurrences for such disasters failed in their performance of their respective roles. Groundbreaking medical advances used to treat the victims include the use of penicillin, methods of treating cutaneous burns, the use of electrolyte balance to aid in determining the ongoing treatment of burn victims, as well as other medical advances improved directly as a result of the fire. Additionally, the first systematic study of grief and survivors’ guilt and the recognition of what is now called Post Traumatic Stress Disorder commenced.Conclusion:Finally the divergent theories of the sources of the fires, how fire codes have changed in the aftermath as well as how the parties that were directly or indirectly responsible for the fire were disciplined by the judicial system will be reviewed.
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Li, Wenjun, Tami Gouveia, Cheryl Sbarra, Nikysha Harding, Kevin Kane, Rashelle Hayes, and Margaret Reid. "Has Boston's 2011 cigar packaging and pricing regulation reduced availability of single-flavoured cigars popular with youth?" Tobacco Control 26, no. 2 (April 6, 2016): 135–40. http://dx.doi.org/10.1136/tobaccocontrol-2015-052619.
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ObjectiveWe evaluated retailer compliance with a cigar packaging and pricing regulation in Boston, Massachusetts, enacted in February 2012, and the regulation's impact on availability of single cigars.MethodsGrape-flavoured Dutch Masters (DM) single-packaged cigars were examined as market indicator. At quarterly intervals from October 2011 to December 2014, availability and price of DM single cigars were observed through professional inspector visits to tobacco retailers in Boston (n=2232) and 10 comparison cities (n=3400). Differences in price and availability were examined between Boston and the comparison cities and across Boston neighbourhoods.ResultsThe mean price of DM single cigars sold in Boston increased from under $1.50 in 2011 to above $2.50 in 2014, consistent with regulation requirements. Rates of retailer compliance reached 100% within 15 months postpolicy enactment based on observed price, and 97% at 30 months postenactment based on final sale prices. There was a 34.5% net decrease in the percentage of Boston retailers selling single cigars from 2011 to 2014. The number of Boston neighbourhoods with 3 or more retailers selling single cigars per 100 youth residents decreased from 12 in 2011 to 3 in 2014. No change in price or per cent of retailers selling single cigars was observed in the comparison cities in the same period.ConclusionsRetailers throughout Boston are in compliance with the regulation. The regulation has been effective in reducing levels and disparities in availability of flavoured single cigars popular with youth across Boston neighbourhoods, regardless of socioeconomic status and racial/ethnic composition.
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Wissman-Weber, Nichole K., and David L. Levy. "Climate adaptation in the Anthropocene: Constructing and contesting urban risk regimes." Organization 25, no. 4 (May 29, 2018): 491–516. http://dx.doi.org/10.1177/1350508418775812.
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The Anthropocene heralds a new era of heightened and unknown risks, particularly regarding the impacts of climate change. This article explores the initial phase of organizing for climate adaptation in Boston, Massachusetts, examining how multiple actors, including business, government, and community organization, are interacting as they attempt to comprehend, assess, and act on this issue. To understand this process of organizing, we develop the concept of ‘risk regime’ as a contingently stabilized system with governance, economic, and discursive dimensions. We draw from theories of risk, organizational resilience, and urban regimes and value regimes to develop the ‘risk regime’ framework, which provides a nuanced view of contestation, collaboration, and accommodation among actors with differential interests, knowledge, and influence on the process. We suggest how the character, evolution, and stabilization of the regime is influenced by competing imaginaries regarding, for example, the nature and manageability of risk, the need for radical change, and the role of markets versus regulations in addressing tensions between economic and sustainability goals. We demonstrate that the regime for adaptation has grown out of the organizational and discursive infrastructure for addressing climate mitigation, or carbon control, but that the unique character of adaptation presents different, and perhaps more difficult challenges.
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Lewandrowski, Kent, Kimberly Gregory, and Donna Macmillan. "Assuring Quality in Point-of-Care Testing: Evolution of Technologies, Informatics, and Program Management." Archives of Pathology & Laboratory Medicine 135, no. 11 (November 1, 2011): 1405–14. http://dx.doi.org/10.5858/arpa.2011-0157-ra.
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Context.—Managing the quality of point-of-care testing (POCT) is a continuing challenge. Advances in testing technologies and the development of specialized informatics for POCT have greatly improved the ability of hospitals to manage their POCT program. Objectives.—To present the evolving role of technology improvement, informatics, and program management as the key developments to ensure the quality of POCT. Data Sources.—This presentation is based on a review of the literature and on our experiences with POCT at the Massachusetts General Hospital (Boston). Conclusions.—Federal and state regulations, along with accreditation standards developed by the College of American Pathologists and The Joint Commission, have established guidelines for the performance of POCT and have provided a strong incentive to improve the quality of testing. Many instruments for POCT have incorporated advanced design features to prevent analytic and operator errors. This, along with the development of connectivity standards and specialized data management software, has enabled remote review of test data and electronic flow of information to hospital information systems. However, documentation of manually performed, visually read tests remains problematic and some POCT devices do not have adequate safeguards to prevent significant errors. In the past 2 decades the structure of a successful POCT management program has been defined, emphasizing the role of POCT managers working in conjunction with a pathology-based medical director. The critical skill set of POCT managers has also been identified. The POCT manager is now recognized as a true specialist in laboratory medicine.
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Schumacher, Melissa, Pamela Durán-Díaz, Anne Kristiina Kurjenoja, Eduardo Gutiérrez-Juárez, and David A. González-Rivas. "Evolution and Collapse of Ejidos in Mexico—To What Extent Is Communal Land Used for Urban Development?" Land 8, no. 10 (October 7, 2019): 146. http://dx.doi.org/10.3390/land8100146.
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The ejido system, based on communal land in Mexico, was transformed to private ownership due to neoliberal trends in the 1990s. Based on the theory of stakeholders being agents of change, this study aimed to describe the land policies that changed the ejido system into private development to show how land tenure change is shaping urban growth. To demonstrate this, municipalities of San Andrés Cholula and Santa Clara Ocoyucan were selected as case studies. Within this context, we evaluated how much ejido land is being urbanized due to real estate market forces and what type of urbanization model has been created. These two areas represent different development scales with different stakeholders—San Andrés Cholula, where ejidos were expropriated as part of a regional urban development plan and Santa Clara Ocoyucan, where ejidos and rural land were reached by private developers without local planning. To analyze both municipalities, historical satellite images from Google Earth were used with GRASS GIS 7.4 (Bonn, Germany) and corrected with QGIS 2.18 (Boston, MA, US). We found that privatization of ejidos fragmented and segregated the rural world for the construction of massive gated communities as an effect of a disturbing land tenure change that has occurred over the last 30 years. Hence, this research questions the roles of local authorities in permitting land use changes with no regulations or local planning. The resulting urbanization model is a private sector development that isolates rural communities in their own territories, for which we provide recommendations.
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Gallagher, Elizabeth, Kathrin Boerner, Yijung Kim, Kyungmin Kim, and Daniela Jopp. "Challenges for Children 65+ Caring for Parents 90+ With Dementia During COVID-19." Innovation in Aging 5, Supplement_1 (December 1, 2021): 139. http://dx.doi.org/10.1093/geroni/igab046.536.
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Abstract With the rise of the novel coronavirus, family caregivers of persons with dementia have been tasked with adapting to an entirely new caregiving landscape. Adult children caring for parents in the ‘oldest old’ age group bear an additional burden. Namely, children that are older adults themselves are navigating the joint vulnerability of both their own and their parents’ aging-related issues (e.g., health problems). The aim of this study was to explore the experiences of dementia caregivers during COVID-19 from the unique perspective of children aged 65 and older caring for parents aged 90 and older. Participants were 30 caregivers from the Boston Aging Together Study with whom we conducted in-depth interviews between March 2020 and February 2021. Thematic analysis revealed key challenges related to COVID-19. Children were worried about the prospect of their parent contracting the virus and took steps to minimize their parent’s exposure, such as discontinuing use of formal supports (e.g., home health aides) or assistance from other family and friends. Forgoing these supports often created greater responsibilities for caregivers as well as contributed to greater social isolation for both child and parent. In situations where parents resided in institutional settings, children were often unable to provide necessary help and support to parents due to restrictions. Caregivers also faced difficulties due to their parent not understanding or practicing COVID-19 regulations and in utilizing alternative means of communication with their parent (e.g., video conferencing). Supports and services should be designed in light of the unique challenges of this group.
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Paul, Edward, Danya Fortess Fullerton, Ellen Cohen, Ellen Lawton, Anne Ryan, and Megan Sandel. "Medical-Legal Partnerships: Addressing Competency Needs Through Lawyers." Journal of Graduate Medical Education 1, no. 2 (December 1, 2009): 304–9. http://dx.doi.org/10.4300/jgme-d-09-00016.1.
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Abstract Background Many low- and moderate-income individuals and families have at least one unmet legal need (for example, unsafe housing conditions, lack of access to food and/or income support, lack of access to health care), which, if left unaddressed, can have harmful consequences on health. Eighty unique medical-legal partnership programs, serving over 180 clinics and hospitals nationwide, seek to combine the strengths of medical and legal professionals to address patients' legal needs before they become crises. Each partnership is adapted to serve the specific needs of its own patient base. Intervention This article describes innovative, residency-based medical-legal partnership educational experiences in pediatrics, internal medicine, and family medicine at 3 different sites (Boston, Massachusetts; Newark, New Jersey; and Tucson, Arizona). This article addresses how these 3 programs have been designed to meet the Accreditation Council for Graduate Medical Education's 6 competencies, along with suggested methods for evaluating the effectiveness of these programs. Training is a core component of medical-legal partnership, and most medical-legal partnerships have developed curricula for resident education in a variety of formats, including noon conferences, grand rounds, poverty simulations and day-long special sessions. Discussion Medical-legal partnerships combine the skill sets of medical professionals and lawyers to teach social determinants of health by training residents and attending physicians to identify and help address unmet legal needs. Medical-legal partnership doctors and lawyers treat health disparities and improve patient health and well-being by ensuring that public programs, regulations, and laws created to benefit health and improve access to health care are implemented and enforced.
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Mindarti, Lely Indah, Akmal Malik, Bambang Supriyono, and Hermawan. "Quality of Regional Election Implementation as Determinant of Performance of Simultaneous Regional Election: Community Trust and Satisfaction as Mediation, and Regulatory Harmonization as Moderation." Review of Pacific Basin Financial Markets and Policies 24, no. 01 (March 2021): 2150008. http://dx.doi.org/10.1142/s0219091521500089.
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The objectives of this research are to analyze how to build the political and managerial balance of government in direct and simultaneous regional elections in Indonesia based on the managerial approach of government and the decentralization approach quantitatively. Data analysis uses the Social Network Analysis (SNA) or Social Network Theory (SNT) approach to map policies using the XL Node and first-order confirmatory factor analysis which is a form of measurement model in the Structural Equation Model (SEM). The population in this study is the Regency/City and Province Organizers of the 2018 elections, which are 88 pairs of Regional Heads/Deputy Regional Heads. The sample of this study was voters who assessed the quality of the elections and other variables, totaling 340 respondents. The results of the study indicate that community trust and community satisfaction can be mediation for the quality of the implementation of regional election to influence the performance of simultaneous regional election. In addition, harmonization of regulations is a moderating variable that can affect the quality of the implementation of regional elections, public trust, and public satisfaction with the performance of simultaneous regional elections. This study conducted a quantification study related to new approaches in building a balance with the managerial approach of governance (Rosenbloom, DH (2015). Public Administration: Understanding Management, Politics, and Law in the Public Sector, 8th ed. Boston, MA: McGraw-Hill; Frederickson, HG (1980). New Public Administration. University of Alabama Press; Frederickson, GN and NA Lynch (1984). The impact of synchronous communication on the problem of electing a leader in a ring. In Proc. 16th Annual ACM Symp. Theory of Computing, Washington, D.C., pp. 493–503. https://doi.org/10.1145/800057.808719 ) and the decentralization approach (Smith, BC (1985). Decentralization: The Territorial Dimension of the State. Taylor & Francis; Smith, BC (2012). Desentralisasi, Dimensi Teritorial Suatu Negara (diterjemahkan oleh Tim MIPI). Jakarta: MIPI).
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Rusuli, Yusufujiang, Lanhai Li, Fadong Li, and Mamattursun Eziz. "Water-level regulation for freshwater management of Bosten Lake in Xinjiang, China." Water Supply 16, no. 3 (January 18, 2016): 828–36. http://dx.doi.org/10.2166/ws.2016.002.
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The Bosten Lake is the largest inland freshwater lake of China, in which water level and salinity fluctuate due to the imbalance between inflows and outflows under climate change and anthropogenic activities. This paper employed system dynamics as an effective methodology to grasp the regulation rules for sustainable freshwater management of the Bosten Lake. Results show the following. (1) Changing of lake water salinity is not only affected by the salinity of water entering and leaving, but is mostly a result of water exchange rate (WER) and the lake level fluctuation. (2) According to the estimated regime of lake level regulations, it is attested that surface water inflow must be larger than outflow about 10.6 × 108 m3 every year. Thus, the Bosten Lake can keep its normal water level. (3) A nonlinear equation was fitted between WER and average salinity of the Bosten Lake. This equation quantifies that when WER equals, or is larger than, 7, the Bosten Lake can be kept as a freshwater lake at all times.
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Firman, Firman. "MERITOKRASI DAN NETRALITAS APARATUR SIPIL NEGARA (ASN) DALAM PENGARUH PILKADA LANGSUNG." Indonesian Journal of Public Administration (IJPA) 3, no. 2 (December 15, 2017): 88–105. http://dx.doi.org/10.52447/ijpa.v3i2.1136.
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Abstract: This study is about the meritocracy system of bureaucracy and the neutrality of civil state apparatus (ASN) in the face of elections to the elections. In various regions there is always a problem of bureaucratic professionalism issues. Despite the various regulations to regulate ASN to be neutral and independent so that the democratic process in this case direct election of the head of the region can run well. However, this issue is always repeated with different schemes for the lust of power and bureaucrat positions that can be facilitated or lifted / accelerated to occupy positions in the bureaucracy. Various rules and regulations were hit or forced only because they became part of the susceptibility when the pilkada was implemented. A regulation about ASN 2014 is expected to filter spoil system problems or promote a bureaucrat in certain positions only because of proximity or for being a successful team during the electionsKeywords: meritocracy system , bureaucracy, election Abstrak: Kajian ini tentang system meritokrasi birorkasi dan netralitas aparatur sipil negara (ASN) dalam menghadapi pilkada sampai dengan pilkada usai. Diberbagai daerah selalu muncul persoalan permasalahan profesionalisme birorkasi. Walaupun sudah lahir berbagai regulasi untuk mengatur agar ASN bisa bersikap netral dan independen agar proses demokrasi dalam hal ini pemilihan langsung kepala daerah bisa berjalan dengan baik. Namun, persoalan ini selalu berulang dengan skema yang berbeda untuk syahwat kekuasaan dan jabatan birokrat yang bisa dimudahkan atau diangkat/dipercepat untuk menduduki posisi dalam birokrasi. Berbagai aturan dan regulasi ditabrak atau dipaksakan hanya karena menjadi bagian suskesi saat pilkada dilaksanakan. Muncul regulasi tentang ASN 2014 diharapkan bisa menfilter persoalan spoil system atau mempromosikan seorang birokrat dalam posisi tertentu hanya gara-gara kedekatan atau karena menjadi tim sukses saat pilkada Kata kunci: Sistem Merit, Birokrasi, Pemilu Albrow, M. (1989). Birokrasi, diterjemahkan oleh Rusli Karim dan Totok Daryanto, PT. Tiara Wacana. Jakarta.Alon-Barkat, S., & Gilad, S. (2016). Political control or legitimacy deficit? Bureaucracies' symbolic responses to bottom-up public pressures. Policy & Politics, 44(1), 41-58.Assessment of hierarchical tendencies in an Indian bureaucracy. International Journal of Public Sector Management, 20(5), 380-391Cascio, W. F. (2006). The economic impact of employee behaviors on organizational performance. California Management Review, 48(4), 41-59.Kaufman, H. (1956). Emerging conflicts in the doctrines of public administration. American Political Science Review, 50(4), 1057-1073.Laski, H. J. (2014). Parliamentary Government in England (works of Harold J. Laski): A Commentary (Vol. 9). Routledge.Martini, R. (2010). Politisasi birokrasi di Indonesia. POLITIKA Jurnal Ilmu Politik MIP, 1(1), 67-74.Nadel, M. V., & Rourke, F. E. (1975). Bureaucracies. Handbook of Political Science, 5, 373-440.Rourke, F. E. (1984). Bureaucracy, Politics, and Public Policy. Boston: Little, Brown. RourkeBureaucracy. Politics, and Public Policy1984.Rourke, F. E. (1992). Responsiveness and neutral competence in American bureaucracy. Public Administration Review, 539-546.Setiyono, B. (2012). Birokrasi Dalam Perspektif “Politik & Administrasi” (Vol. 1). NUANSA.Soebhan, S. R. (2000). Model Reformasi Birokrasi Indonesia. Jakarta: PPW LIPI.Sudirman ://makassar.tribunnews.com/2016/08/26/daftar-nama-nama-pejabat-soppeng-yang-baru-dilantik diakses pada tanggal 2/10/2017Thoha, M., & Organisasi, P. (1993). konsep dasar dan Aplikasinya. Jakarta: Rajawali Pers.Thompson, J. D. (1967). Organizations in action: Social science bases of administrative theory. Transaction publishers.Woo, K. H. (2015). Recruitment Practices in the Malaysian Public Sector: Innovations or Political Responses?. Journal of Public Affairs Education, 229-246.Janesick, J., Pinter, J., Potter, R., Elliot, T., Andrews, J., Tower, J., ... & Bishop, J. (2009, August). Fundamental performance differences between CMOS and CCD imagers: part III. In Proc. SPIE (Vol. 7439, p. 743907).
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Ahuja, Rakesh, Akash Desai, Jung Hyun Yun, Eric Soltycki, Vinit Khanna, and Balasubramani Natarajan. "Road to becoming Y-90 authorized user as an integrated vascular and interventional radiology resident (NRC alternate pathway)." American Journal of Interventional Radiology 5 (July 9, 2021): 11. http://dx.doi.org/10.25259/ajir_19_2021.
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Yttrium-90 (Y-90) radioembolization, also called transarterial radioembolization (TARE), is a catheter-directed therapy for direct delivery of internal radiation to tumors in the form of microspheres. It is currently available in two forms, either as a constituent of glass microspheres called TheraSphere® (BTG Ltd., London, UK [now Boston Scientific, Marlborough, MA, USA]) or as a biocompatible resin-based microsphere called SIR-Spheres® (Sirtex Medical Ltd., Woburn, MA, USA). Once these microspheres are delivered to the tumor through an arterial pathway, they are embedded within the tumor microcirculation and emit β-radiation at therapeutic levels. TARE is a commonly used treatment for unresectable primary or secondary hepatic malignancies and has led to improved survival rates and increased success rates in downstaging patients before liver resection or transplantation. Immediately following the pre-treatment angiogram, each patient undergoes a nuclear medicine study, otherwise known as technetium (99mTc) macroaggregated albumin scan, to determine the amount of radiotracer that has accumulated in the lungs (lung shunt fraction). Finally, after several calculations, the appropriate radiation dose to be delivered to the tumor is determined. While the technical aspects of radioembolization are quite complex, the collective clinical experience presented in the literature supports the use of Y-90 radioembolization for unresectable hepatic malignancies. Those ordering and administering radioembolization particles must be deemed an authorized user (AU) by the Nuclear Regulatory Commission (NRC). The NRC defines an AU as the individual responsible for ensuring that radioactive materials are handled and used safely and following NRC regulations and the terms and conditions of the NRC license. The NRC has published licensing guidance on Y-90 brachytherapy with the 10th revision released on November 8, 2019. This guidance has outlined specific requirements for obtaining a license for the use of TheraSphere and SIR-Spheres. Following the revised licensure guidelines from the NRC on Y-90 usage, a conditional authorization has been obtained at our institution by the PGY-6 interventional radiology/diagnostic radiology (IR/DR) resident. While the full guidelines and extensive alternative requirements can be found online, we will highlight the specific guidelines applicable to and fulfilled by IR/DR residents. The traditional ABR pathway takes approximately 18 months after graduation, including passing the ABR certification examination to become an AU. With the proposed alternate pathway, trainees will potentially become AU immediately after graduation. The primary aim of this submission is to describe the process for obtaining conditional authorization for Y-90 microspheres for PGY-6 IR/DR residents.
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Downs, Charles A., and My N. Helms. "Regulation of ion transport by oxidants." American Journal of Physiology-Lung Cellular and Molecular Physiology 305, no. 9 (November 1, 2013): L595—L603. http://dx.doi.org/10.1152/ajplung.00212.2013.
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Ion channels perform a variety of cellular functions in lung epithelia. Oxidant- and antioxidant-mediated mechanisms (that is, redox regulation) of ion channels are areas of intense research. Significant progress has been made in our understanding of redox regulation of ion channels since the last Experimental Biology report in 2003. Advancements include: 1) identification of nonphagocytic NADPH oxidases as sources of regulated reactive species (RS) production in epithelia, 2) an understanding that excessive treatment with antioxidants can result in greater oxidative stress, and 3) characterization of novel RS signaling pathways that converge upon ion channel regulation. These advancements, as discussed at the 2013 Experimental Biology Meeting in Boston, MA, impact our understanding of oxidative stress in the lung, and, in particular, illustrate that the redox state has profound effects on ion channel and cellular function.
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Sung, Yu, Daniel J. Cantliffe, and Russell T. Nagata. "Seed Developmental Temperature Regulation of Thermotolerance in Lettuce." Journal of the American Society for Horticultural Science 123, no. 4 (July 1998): 700–705. http://dx.doi.org/10.21273/jashs.123.4.700.
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Lettuce (Lactuca sativa L.) seeds can fail to germinate at temperatures above 24 °C. The degree of thermotolerance is thought to be at least partly related to the environment under which the seed developed. In order to study the effects of temperature during seed development on subsequent germination, various lettuce genotypes were screened for their ability to germinate at temperatures ranging from 20 to 38 °C. Seeds of the selected genotypes `Dark Green Boston' and `Valmaine' (thermosensitive), `Floricos 83', `Everglades', and PI 251245 (thermotolerant) were produced at 20/10, 25/15, 30/20, and 35/25 °C day/night temperature regimes in plant growth chambers. Seeds were germinated on a thermogradient bar from 24 to 36 °C under 12 h light/dark cycles. As germination temperature increased, the number of seeds that failed to germinate increased. Above 27 °C, seeds matured at 20/10 or 25/15 °C exhibited a lower percent germination than seeds that matured at 30/20 or 35/25 °C. Seeds of `Dark Green Boston' and `Everglades' that matured at 30/20 °C exhibited improved thermotolerance over those that matured at lower temperatures. Seeds of `Valmaine' produced at 20/10 °C exhibited 40% germination at 30 °C, but seeds that matured at higher temperatures exhibited over 95% germination. Germination of `Valmaine' at temperatures above 30 °C was not affected by seed maturation temperature. The upper temperature limit for germination of lettuce seed could thus be modified by manipulating the temperature during seed production. The potential thermotolerance of seed thereby increased, wherein thermosensitive genotypes became thermotolerant and thermotolerant genotypes (e.g., PI251245) germinated fully at 36 °C. This information is useful for improving lettuce seed germination during periods of high soil temperature, and can be used to study the biology of thermotolerance in lettuce.
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Zenkina, Elena V. "STRATEGIES AND METHODS FOR DIGITAL BUSINESS TRANSFORMATION AND THEIR USE IN COMPANY MANAGEMENT PROCESSES." Science and art of management / Bulletin of the Institute of Economics, Management and Law of the Russian State University for the Humanities, no. 1 (2023): 10–25. http://dx.doi.org/10.28995/2782-2222-2023-1-10-25.
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The article reflects strategies and methods that ensure the efficiency and performance of managing existing business processes in small and mediumsized enterprises through the use of digital technologies and digitized data. It analyzes in detail the UK’s experience in developing digital transformation policies for small and medium-sized businesses. The relevance of the study is due to the fact that in the 21st century it is a strong economic system that determines the stability and well-being of modern states. Today it is impossible to imagine a market economy without small and medium-sized businesses. In conditions of global instability, the experience of Great Britain is of particular interest, which, after more than forty years of membership in the European Union, decided to withdraw from the union and since then has been in search of new optimal models of internal and external functioning. Taking into account the qualitatively new stage of development at which the United Kingdom is now, as well as the challenges such as the consequences of Brexit, the COVID-19 pandemic, world trade wars, rising energy prices, etc., the analysis of development management and the role of the digital transformation of small and medium-sized enterprises on the example of Great Britain can be of applied use to research economists and government officials in the process of implementing appropriate measures in other countries. The research methodology includes a set of general scientific methods; historical, logical, comparative, graphic and statistical. An assessment of the impact of the innovative small and medium-sized enterprises on UK economic growth was formulated. That served as a basis for the short-term prognosis building in the development of the latter. Scientific innovation consists in a comprehensive study of strategies and methods that ensure the efficiency and performance of managing existing business processes in small and medium-sized enterprises through the use of digital technologies. In particular, the author analyzes programs aimed at developing innovations and their introduction into the real sector of the economy. She studies the UK’s experience in implementing digital transformation policies and assesses its impact on economic growth. Based on the results obtained, a shortterm forecast of trends in the level of economic sustainability of innovative small and medium-sized enterprises is made. The information base of the study was official documents and reports of the UK government, especially the Department for Business, Energy and Industrial Strategy, the Department for International Trade, the Office for National Statistics, UK legislation and regulations, analytical materials of the international consulting companies “McKinsey and Company”, “Boston Consulting Group” and “Bain and Company”. Reviews of the world trade statistics of the WTO, monographs and scientific articles of Russian and foreign specialists, as well as resources of the global Internet.
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Glaeser, Edward L., and Bryce A. Ward. "The causes and consequences of land use regulation: Evidence from Greater Boston." Journal of Urban Economics 65, no. 3 (May 2009): 265–78. http://dx.doi.org/10.1016/j.jue.2008.06.003.
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Skeer, Margie, Michelle L. Land, Debbie M. Cheng, and Michael B. Siegel. "Smoking in Boston Bars Before and After a 100% Smoke-Free Regulation." Journal of Public Health Management and Practice 10, no. 6 (November 2004): 501–7. http://dx.doi.org/10.1097/00124784-200411000-00005.
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Steele, Rachel R., Daniel R. Rovenpor, Brian Lickel, and Thomas F. Denson. "Emotion regulation and prejudice reduction following acute terrorist events: The impact of reflection before and after the Boston Marathon bombings." Group Processes & Intergroup Relations 22, no. 1 (June 7, 2017): 43–56. http://dx.doi.org/10.1177/1368430217706182.
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Research suggests that regulating negative emotional responses to threatening events can help reduce outgroup bias. The present research examined the effect of emotion regulation strategies on outgroup bias during relatively benign versus threatening time periods. Participants were assigned to regulate their emotions (reflection, rumination, or control) while reading a reminder of a past terrorist event and then reported their anger and bias toward Muslims. The bombings at the 2013 Boston Marathon occurred during data collection, which allowed us to examine the effect of emotion regulation on bias before versus after these events via a 3 (emotion regulation) x 2 (timing of bombings) between-subjects design. A two-way interaction between emotion regulation condition and timing emerged on bias and anger. Reflection (compared to rumination or control) reduced bias and anger toward Muslims but only after the bombings. The reduction in anger mediated the effect of reflection on bias only after the bombings. The results provide evidence that reflection is effective at reducing bias when people are experiencing an intense outgroup threat.
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B. Bringas, Abraham, and Arthur B. Almario. "ASSESSMENT ON THE IMPLEMENTATION OF BARANGAY MICRO BUSINESS ENTERPRISES ACT OF 2002 RELATIVE TO THE PROFITABILITY OF FOOD BUSINESSES IN VICTORIA, LAGUNA." Business, Organizations and Society 1, no. 1 (2023): 08–14. http://dx.doi.org/10.26480/bosoc.01.2023.08.14.
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Barangay Micro Business Enterprise (BMBE) law was enacted in 2002 in the Philippines to promote the growth of small and micro-enterprises in the food industry by providing tax incentives and simplified business registration procedures. This study aimed to analyze the effectiveness of BMBE implementation in the food industry, its impact on business profitability, and identify areas for improvement. A survey was conducted on 30 BMBE-registered sole proprietor food businesses in Victoria, Laguna, using a quantitative research method. The findings showed that the BMBE Act of 2002 has benefited micro- enterprises in the food industry, helping them reduce labor costs, comply with regulations, improve their financial status, and allocate more resources for economic expansion and growth. The study highlights the importance of government support for small businesses and suggests targeted interventions or support programs. The researcher recommends further research and promotion of BMBE registration, consistent and effective implementation, and guidelines for monitoring and evaluation.
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Seller, Stephanie L., Cora Roelofs, Paul A. Shoemaker, Nancie N. Nguyen, and Tuan D. Nguyen. "Improving Boston Nail Salon Indoor Air Quality Through Local Public Health Regulation, 2007–2019." American Journal of Public Health 109, no. 12 (December 2019): 1711–13. http://dx.doi.org/10.2105/ajph.2019.305329.
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Ma, Xian-Yong, Wei Qiao Qiu, Caren E. Smith, Laurence D. Parnell, Zong-Yong Jiang, Jose M. Ordovas, Katherine L. Tucker, and Chao-Qiang Lai. "Association betweenBDNFrs6265 and Obesity in the Boston Puerto Rican Health Study." Journal of Obesity 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/102942.
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Brain-derived neurotrophic factor (BDNF) has been associated with regulation of body weight and appetite. The goal of this study was to examine the interactions of a functional variant (rs6265) in theBDNFgene with dietary intake for obesity traits in the Boston Puerto Rican Health Study.BDNFrs6265 was genotyped in 1147 Puerto Rican adults and examined for association with obesity-related traits. Men (n=242) with the GG genotype had higher BMI (P=0.009), waist circumference (P=0.002), hip (P=0.002), and weight (P=0.03) than GA or AA carriers (n=94). They had twice the risk of being overweight (BMI≥25) relative to GA or AA carriers (OR = 2.08, CI = 1.02–4.23, andP=0.043). Interactions between rs6265 and polyunsaturated fatty acids (PUFA) intake were associated with BMI, hip, and weight, and n-3 : n-6 PUFA ratio with waist circumference in men. In contrast, women (n=595) with the GG genotype had significantly lower BMI (P=0.009), hip (P=0.029), and weight (P=0.027) than GA or AA carriers (n=216). Women with the GG genotype were 50% less likely to be overweight compared to GA or AA carriers (OR = 0.05, CI = 0.27–0.91, andP=0.024). In summary,BDNFrs6265 is differentially associated with obesity risk by sex and interacts with PUFA intake influencing obesity traits in Boston Puerto Rican men.
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Shi, Qiang, Changhong Yan, and Peng Yu. "Simulation evaluation of groundwater resources in southeastern Bosten Lake based on GMS." E3S Web of Conferences 79 (2019): 03020. http://dx.doi.org/10.1051/e3sconf/20197903020.
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Bosten Lake is located in Yanqi Basin of Xinjiang. A working area in the southeast of China is influenced by the regulation of Bosten Lake, and the transitional zone of climate in the north and south of Xinjiang, forming a climate of large evaporation, dry and little rain, and groundwater is a very important fresh water resource. In order to find out the composition of groundwater resources in the working area, the groundwater steady flow model is established by using the data of borehole, well, pumping test and so on, and the groundwater resources in this area are evaluated. The groundwater exploitation mode in the simulated area is evaluated. The results show that: the exploitable groundwater resources in the simulated area is about 22.045 million m3/a. Changing the mode of agricultural water use under the existing groundwater equilibrium condition can effectively reduce the waste of groundwater resources.
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Walker, Christopher James, Shirong Li, Yi Chai, Jatin J. Shah, Sharon Shacham, Suzanne Lentzsch, and Yosef Landesman. "Effects of weekly selinexor, bortezomib, dexamethasone (XVd) versus standard twice weekly bortezomib and dexamethasone (Vd) on RAS-mutated previously treated multiple myeloma (MM)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 8027. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8027.
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8027 Background: Activating mutations of the RAS genes NRAS, KRAS, and HRAS ( RASmut) occur in up to 50% of MM and portend poor survival and high recurrence rates. MM cells with RASmut are susceptible to inhibition of germinal center kinase (GCK), resulting in IKAROS degradation independent of cereblon (CRBN). Selinexor is a selective inhibitor of nuclear export (SINE) compound that can induce IKAROS degradation through CRBN-independent pathways to overcome immunomodulatory drug resistance. We explored the benefit of selinexor treatment for pts with RASmut MM. Methods: In the randomized BOSTON study, pts with MM after 1-3 therapies received weekly XVd or twice weekly Vd. In the single-arm STORM study pts with penta-treated, triple class refractory MM were treated with twice weekly Xd. Both treatment regimens are now FDA approved. Mutations were assessed post-hoc by exome sequencing of 119 and 52 pts from BOSTON and STORM, respectively. Pts were considered RASmut if their MM had NRAS, KRAS or HRAS mutations in codons 12, 13 or 61. Results: There were 54 pts (45%) with RASmut in BOSTON (XVd = 26, Vd = 28), and 17 (33%) in STORM. In BOSTON, pts with RASmut MM treated with XVd had significantly longer progression-free survival (PFS) than those treated with Vd (median [med] = 12.9 vs 6.7 months [mo], hazard ratio [HR] = 0.48 [95% CI 0.24-0.97], p = 0.039). For pts treated with Vd, those with RASmut had significantly shorter overall survival (OS) compared to RASwild-type (WT) (med = 16.8 mo vs not reached [NR], HR = 2.87 [95% CI 1.03-7.99], p = 0.035). PFS was not significantly different (med = 6.74 vs 9.82 mo, HR = 1.64 [95% CI 0.88-3.07], p = 0.122). Amongst pts on XVd, there was no difference in survival between RASmut and RASWT pts (PFS: med = 12.8 vs 12.9 mo, HR = 1.08 [95% CI 0.52-2.26], p = 0.83; OS: med = NR vs NR, HR = 0.94 [95% CI 0.36-2.45], p = 0.91). In STORM, pts with RASmut had shorter OS compared to RASwt pts (med = 6.1 vs NR, HR = 2.05 [95% CI 1.22-5.19], p = 0.010). Preliminary studies to explore the mechanisms of action related to RASmut MM sensitivity to XVd demonstrated that selinexor treatment in vitro leads to downregulation of GCK. Conclusions: Despite typically having the worst outcomes, pts with RASmut MM had a similar benefit from XVd as RASWT MM, showing that the XVd combination can overcome RASmut. Mechanistically, selinexor induced down regulation of GCK and enhanced killing of RASmut MM cells. With a manageable safety profile, the XVd regimen could provide a viable treatment option to improve survival of pts with MM with RAS mutations. Clinical trial information: NCT03110562. [Table: see text]
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Champine, Robey B., and Sara K. Johnson. "Towards the Promotion of Positive Development among Boys in Challenging Contexts: A Mixed-Methods Study of Engagement in the Scoutreach Initiative." Journal of Youth Development 12, no. 4 (December 13, 2017): 16–37. http://dx.doi.org/10.5195/jyd.2017.521.
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Engagement in youth development programs reflects the quality of young people’s program-related experiences. However, more research is needed that explores cognitive, emotional, and behavioral dimensions of engagement in programs that serve underrepresented youth of color. The present cross-sectional and mixed-methods study assessed potential relations among dimensions of engagement in the Boston-area Scoutreach initiative, character attributes, self-perceived school competence, and intentional self-regulation. We analyzed data from 32 Scouts (Mage = 9.97 years, SD = 2.46, Range = 6 to 14), 32 parents/guardians, and five Scoutreach leaders. Scouts demonstrated that they were cognitively, emotionally, and behaviorally engaged in Scoutreach, and these dimensions were related differentially to indicators of healthy development. Qualitative data elucidated key aspects of Scoutreach (e.g., camping, peer relationships) that were linked to youth engagement. We discuss limitations of the present study and implications for future research and practice.
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Gordan, John, Adriana Pitea, Rigney E. Turnham, Manon Eckhardt, Gwendolyn M. Jang, Huat Lim, Alex L. Choi, et al. "Abstract PO017: HBV alters YAP regulation in liver cancer by remodeling PP2A complexes." Clinical Cancer Research 28, no. 17_Supplement (September 1, 2022): PO017. http://dx.doi.org/10.1158/1557-3265.liverca22-po017.
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Abstract Viral hepatitis promotes hepatocellular carcinoma (HCC) initiation by inducing inflammation, cellular stress and cell death. However, the cell-intrinsic effects of viral infection in advanced HCC remain unclear. We used affinity purification mass spectrometry to develop a complete map of 145 interactions among Hepatitis B Virus (HBV) and host proteins in the HUH7 HCC tumor cell line, identifying known and novel HBV/host protein-protein interactions. We integrated this map with HCC genomes, identifying 61 proteins with preferential mutation in non-HBV HCC, suggesting that their interaction with HBV plays a role in cancer. Focusing on proteins that directly interact with the HBV oncoprotein X (HBx), we found that HBx rewires the effect of the PP2A phosphatase on HCC signaling. HBx binding excluded striatin-family regulatory subunits from the PP2A complex, causing Hippo kinase activation. This effect creates a requirement for integrin signaling to mTOR complex 2 to maintain expression of the YAP oncoprotein, critical for HCC growth. Thus, HBV rewires HCC signaling and may promote targetable dependencies. Citation Format: John Gordan, Adriana Pitea, Rigney E Turnham, Manon Eckhardt, Gwendolyn M Jang, Huat Lim, Alex L Choi, Sourav Bandyopadhyay, Danielle Swaney, Kevan Shokat, Trey Ideker, Nevan Krogan. HBV alters YAP regulation in liver cancer by remodeling PP2A complexes [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO017.
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Giuliani, Marco. "Michael D. Reagan, Regulation. The Politics of Policy, Boston, Little, Brown & Co., 1987, pp. 241, St. 12.95." Italian Political Science Review/Rivista Italiana di Scienza Politica 19, no. 1 (April 1989): 150–52. http://dx.doi.org/10.1017/s0048840200017585.
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Srinivasan, Sneha, Priscilla Tang, Karthikeyan Mythreye, and Nadine Hempel. "Abstract A030: Regulation of SIRT3 overexpression in anchorage independent ovarian cancer." Cancer Research 84, no. 5_Supplement_2 (March 4, 2024): A030. http://dx.doi.org/10.1158/1538-7445.ovarian23-a030.
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Abstract Ovarian cancer remains the most lethal gynecological malignancy, and late-stage diagnosis and significant metastatic spread are prominent contributors to its lethality. To achieve optimal metastasis, ovarian tumor cells must modify their response to heightened oxidative stress to ensure their survival. One crucial mechanism of this modification involves the scavenging of mitochondrial superoxide anions by superoxide dismutase (SOD2). Mitochondrial Sirtuin Deacetylase 3 (SIRT3) deacetylates SOD2 to enhance its antioxidant capacity, facilitating the conversion of superoxide (O2−) to H2O2. We have shown that this antioxidant mechanism helps to preserve mitochondrial function of high grade serous ovarian cancer cell lines, enhances cellular survival in anchorage-independence, and is necessary for in vivo metastatic spread to the omentum. Expression of both SOD2 and SIRT3 increase in ovarian cancer cells following matrix detachment, and we found that SOD2 is regulated by both transcription and translation, resulting in rapid and sustained increases in this mitochondrial antioxidant in response to matrix detachment. Presently, we are exploring the mechanisms of SIRT3 regulation, as this deacetylase is necessary for the maintenance of SOD2 activity in anchorage independent conditions. We find that active transcription is required for the increased SIRT3 expression observed in anchorage independence and are currently investigating the role NF-kB plays as a critical transcription factor of SIRT3 in this context. Understanding the regulation of SIRT3 will shed light on ovarian cancer cell survival adaptations during metastasis and provide potential insights into new targets for therapeutic interventions. Citation Format: Sneha Srinivasan, Priscilla Tang, Karthikeyan Mythreye, Nadine Hempel. Regulation of SIRT3 overexpression in anchorage independent ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A030.
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Lee, Changhu, Min Kim, Chanho Park, Woobeen Jo, and Jiyoung Park. "Abstract A063: Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia." Molecular Cancer Therapeutics 22, no. 12_Supplement (December 1, 2023): A063. http://dx.doi.org/10.1158/1535-7163.targ-23-a063.
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Abstract Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, we show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where recombination signal binding protein for immunoglobulin kappa J region (RBPJ), E1A binding protein p300 (P300), and SET domain containing 1A (SETD1A) are recruited to upregulate Nrg1 expression. Deletions in RBPJ-binding sites causes hyperglycemia-controlled Nrg1 levels to be downregulated, resulting in decreased tumor growth in vitro and in vivo. Mice with modest-temporary hyperglycemia, induced by low-dose short-exposure streptozotocin, display accelerated tumor growth and lapatinib resistance, whereas combining lapatinib with N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S42 phenylglycine t-butyl ester (DAPT) ameliorates tumor growth under these modest hyperglycemic conditions by inhibiting NOTCH and EGFR superfamilies. NOTCH activity is correlated with NRG1 levels, and high NRG1 levels predicts poor outcomes, particularly in HER2-positive breast cancer patients. Our findings highlight the hyperglycemia-linked epigenetic modulation of NRG1 as a potential therapeutic strategy for treating breast cancer patients with diabetes. Citation Format: Changhu Lee, Min Kim, Chanho Park, Woobeen Jo, Jiyoung Park. Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A063.
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Berg, Sanford V. "Incentive Regulation and the Regulation of Incentivesby Glenn Blackmon(Kluwer Academic Publishers, Dordrecht and Boston, 1994), pp. x + 133, US$69.95. ISBN 0 7923 9470 4." Prometheus 14, no. 1 (June 1996): 113–15. http://dx.doi.org/10.1080/08109029608632026.
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Dalasanur Nagaprashantha, Lokesh Prasad Gowda, Tatjana Talamantes, Jyotsana Singhal, Sanjay Awasthi, Sharad S. Singhal, and Laszlo Prokai. "The impact of novel compound 2'-hydroxyflavanone on proteomic networks of VHL-mutant renal cell carcinoma." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e13557-e13557. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e13557.
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e13557 Background: Von Hippel-Lindau (VHL) tumor suppressor is a major genetic factor that determines hypoxic acclimatization and response to therapy in renal cell carcinoma (RCC). Our initial studies revealed that 2'-Hydroxyflavanone (2HF) effectively inhibits the survival of VHL-mutant RCC. Hence, we performed proteomic analyses to study the signaling networks of clinical significance that are regulated by 2HF in VHL-mutant RCC. Methods: The 786-O cells, an established cell line from a male Caucasian patient, were provided by William Kaelin Jr., MD, Harvard Medical School, Boston, MA. The cells were cultured either in the presence or absence of 50 μM 2HF for 48 h in RPMI medium at 37°C in 5% CO2 and lysed in a buffer containing 6M urea. The lysate (200 µg of protein) was reduced, alkylated and digested with trypsin. Tryptic digests were desalted using a C-18 cartridge (Waters, USA) and subjected to liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses on linear ion trap–Fourier transform ion cyclotron resonance tandem mass spectrometer (LTQ-FT, Thermo) coupled to an Eksigent nano-LC system. MS/MS spectra were searched against human protein sequence database using Mascot (Matrix Science), and protein identifications were validated by Scaffold (version 3.0, Proteome Software). Quantifications were performed by extracted peptide intensities (Progenesis LC-MS, Nonlinear Dynamics). Results: 2HF treatment lead to up-regulation of 21 proteins including protein disulfide-isomerase A4 and macrophage migration inhibition factor. 2HF treatment lead to down-regulation of 23 proteins including vimentin, HSP90AB1, 14-3-3 gamma and glutaminase. The network analyses revealed that the identified proteins form critical nodes of regulation of vital tumor proteins like MAP3K14, ERK1/2, Myc and P53. Conclusions: Proteomic analyses of 2HF treated VHL-mutant RCC revealed a striking regulation of proteins of importance in RCC survival, invasion and metastases. The critical nodes of regulation as identified by the network analyses could facilitate further studies on the development of network targeting therapies using 2HF and other anti-cancer compounds for the effective management of VHL-mutant RCC.
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Hofmann, Stefan G., Nicola Petrocchi, James Steinberg, Muyu Lin, Kohki Arimitsu, Shelley Kind, Adriana Mendes, and Ulrich Stangier. "Loving-Kindness Meditation to Target Affect in Mood Disorders: A Proof-of-Concept Study." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/269126.
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Conventional treatments for mood disorders primarily focus on reducing negative affect, but little on enhancing positive affect. Loving-kindness meditation (LKM) is a traditional meditation practice directly oriented toward enhancing unconditional and positive emotional states of kindness towards oneself and others. We report here two independent and uncontrolled studies carried out at different centers, one in Boston, USA (n= 10), and one in Frankfurt, Germany (n= 8), to examine the potential therapeutic utility of a brief LKM group intervention for symptoms of dysthymia and depression. Results at both centers suggest that LKM was associated with large-sized effects on self-reported symptoms of depression (d= 3.33 and 1.90), negative affect (d= 1.98 and 0.92), and positive affect (d= 1.63 and 0.94). Large effects were also found for clinician-reported changes in depression, rumination and specific positive emotions, and moderate effects for changes in adaptive emotion regulation strategies. The qualitative data analyses provide additional support for the potential clinical utility of the intervention. This proof-of-concept evaluation of LKM as a clinical strategy warrants further investigation.
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Palacios, Natalia, Tammy Scott, Neha Sahasrabudhe, Xiang Gao, and Katherine L. Tucker. "Lower Plasma Vitamin B-6 is Associated with 2-Year Cognitive Decline in the Boston Puerto Rican Health Study." Journal of Nutrition 149, no. 4 (April 1, 2019): 635–41. http://dx.doi.org/10.1093/jn/nxy268.
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ABSTRACT Background Despite its important role in cognitive development and regulation of nervous system function, vitamin B-6 has been under-studied in relation to cognitive aging. Objective We investigated whether plasma pyridoxal-5'-phosphate (PLP, vitamin B-6) concentrations were associated with cognitive function and subsequent cognitive decline. Methods In a longitudinal study of 949 participants (aged 45–75 y at baseline; 70% women) from the Boston Puerto Rican Health Study cohort, we examined the association between baseline plasma PLP and baseline cognitive function and 2-y cognitive decline. Cognitive function was assessed with an in-person 7-test cognitive battery, at baseline and 2-y follow-up. We also used logistic regression to estimate the odds of major 2-y decline in global cognitive function (defined as decline ≥1 SD below the mean), as well as decline in executive function and memory. We also used multivariable linear regression to calculate adjusted mean differences in cognitive scores, and 95% CIs, across tertiles of plasma PLP at baseline, as well as cross-sectional and longitudinal associations with individual test scores. Results In analyses adjusted for potential confounders, the OR of having a major 2-y decline in global cognitive function was 2.46 (95% CI: 1.49, 4.05; P-trend: 0.001) among participants in the lowest tertile of PLP compared with those in the top tertile of PLP. The association of PLP with cognition was stronger in participants older than 55 y at baseline (OR for bottom to top tertile: 4.58; 95% CI: 2.02, 10.35; P-interaction: 0.01) compared with those 55 y old or younger, as well as in ever smokers (OR for bottom to top tertile: 2.99; 95% CI: 1.45, 6.19; P-interaction: 0.02) compared with never smokers. Conclusions Lower baseline plasma PLP was associated with increased odds of 2-y cognitive decline in a cohort of Boston area Puerto Ricans. The association was stronger among older participants and among ever smokers.
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Kafle, Chandra Mani, and Daphne W. Bell. "Abstract B007: Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor." Clinical Cancer Research 30, no. 5_Supplement (March 1, 2024): B007. http://dx.doi.org/10.1158/1557-3265.endo24-b007.
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Abstract Serous endometrial cancer (SEC) is an aggressive form of cancer that frequently exhibits recurrent somatic mutations in FBXW7 at residues 465, 479, and 505. FBXW7 is a tumor suppressor and is part of a Skp1-Cullin-F-box containing (SCF) complex that targets various proteins, including certain oncoproteins, for ubiquitin-mediated proteasomal degradation. FBXW7 interacts with Cdc4 phosphodegron (CPD) motif(s) within substrate proteins. We previously reported upregulation of peptidyl arginine deiminase 2 (PADI2), a potentially druggable protein, in FBXW7-mutant SEC cell lines compared to the isogenic FBXW7-wildtype cells. The purpose of this study is to investigate the mechanism by which FBXW7 regulates PADI2 levels. We searched for the CPD motif in the PADI2 protein sequence. We used co-immunoprecipitation and immunoblotting to study FBXW7-PADI2 interactions after transiently transfecting HEK293 cells with constructs expressing MYC-tagged FBXW7 and/or HA-tagged PADI2, in the presence or absence of bortezomib. We identified three putative CPD motifs in PADI2, leading us to hypothesize that wildtype FBXW7 binds PADI2 and thus targets PADI2 for degradation via a proteasome-dependent mechanism. Our experimental data show that FBXW7 interacts with PADI2, in the presence of bortezomib, a proteasome inhibitor, in transiently transfected HEK293 cells. Additionally, we have shown that mutation of the putative CPD motifs of PADI2 abrogates the PADI2-FBXW7 interaction. Our findings implicate PADI2 as a novel substrate of the FBXW7 tumor suppressor. Citation Format: Chandra Mani Kafle, Daphne W. Bell. Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B007.
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Taniue, Kenzui, Yusuke Mizukami, and Nobuyoshi Akimitsu. "Abstract B059: RNA exosome component EXOSC4 amplified in multiple cancer types is required for the pancreatic cancer cell survival via the regulation of BIK and SESN2 mRNA." Cancer Research 82, no. 22_Supplement (November 15, 2022): B059. http://dx.doi.org/10.1158/1538-7445.panca22-b059.
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Abstract RNA decay plays a crucial role in the post-transcriptional regulation of gene expression. The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. The RNA exosome is composed of a catalytically inactive barrel structure of nine core subunits (known as EXO9) that achieves its catalytic activity via the interaction with the exoribonuclease exosome component 10 (EXOSC10), the exo/endo-ribonuclease DIS3, and the two DIS3-like proteins (the exoribonucleases DIS3L and DIS3L2). Moreover, exosome activity is regulated by associated co-factors and RNA-binding adaptor proteins that recruit the exosome to its many targets. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis in pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells. Citation Format: Kenzui Taniue, Yusuke Mizukami, Nobuyoshi Akimitsu. RNA exosome component EXOSC4 amplified in multiple cancer types is required for the pancreatic cancer cell survival via the regulation of BIK and SESN2 mRNA [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B059.
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Mischel, Paul. "Abstract IA017: Extrachromosomal DNA (ecDNA): Cancer’s dynamic circular genome." Cancer Research 84, no. 3_Supplement_2 (February 1, 2024): IA017. http://dx.doi.org/10.1158/1538-7445.canevol23-ia017.
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Abstract Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA poses one of the greatest challenges for cancer patients, affecting children and adults and women and men, with a wide variety of cancer types. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. ecDNA, because of its non-chromosomal inheritance, drives high-copy number oncogene amplification and enables tumors to evolve their genomes rapidly, contributing to treatment resistance and shorter survival for patients. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription. In this talk, I will discuss recent collaborative discoveries that highlight how the higher order, spatial organization of ecDNA, and its mechanism of inheritance, contributes to aggressive tumorigenesis, accelerated evolution, and treatment resistance. Citation Format: Paul Mischel. Extrachromosomal DNA (ecDNA): Cancer’s dynamic circular genome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA017.
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Brickman, Sophie, Leia Y. Saltzman, Steven L. Bistricky, and Ellen J. Wright. "Predicting profiles of post-trauma adaptation in first responders and civilians after the 2013 Boston Marathon bombings: The role of distress, growth, and emotion regulation." Journal of Emergency Management 20, no. 4 (September 1, 2023): 311–22. http://dx.doi.org/10.5055/jem.0754.
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Introduction: Responses to trauma are often characterized either by the presence or absence of psychological distress; however, the process of adapting after trauma also includes potential positive change. While some studies document that the majority of individuals exposed to single event terrorism report low levels of psychological distress, more research is needed to understand different adaptation profiles following this type of trauma, and the factors that might predict responses.
Methods: We examined post-trauma responses in 257 first responders/medical professionals (66.8 percent) and civilians (33.2 percent) exposed to the 2013 Boston Marathon Bombings. Data for post-trauma profiles—post-traumatic growth (PTG), posttraumatic stress, and emotion regulation—and profile predictors—trauma proximity, trauma history, and coping flexibility—were collected approximately 2.5 years after the bombings. Latent profile analysis identified response profiles, and multinomial logistic regression identified demographic, event-specific, and psychological predictors of profile membership.
Results: Four profiles emerged: (1) symptomatic, (2) resistant, (3) resilient, and (4) struggling growth. First responder role decreased the odds of belonging to the struggling growth profile, as compared to the symptomatic profile. Greater coping flexibility and adaptive emotion regulation increased the odds of membership in the struggling growth, rather than symptomatic profile.
Conclusion: A subset of individuals experiencing post-traumatic stress symptoms years after trauma exposure may also be utilizing flexible, adaptive coping strategies and experiencing PTG. First responders may have difficulty experiencing simultaneous distress and growth, and interventions designed to promote healthy post-trauma adaptation for this population could be tailored accordingly.
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Konjicija-Kovač, Anita. "Teorijska promišljanja o informacijskoj politici u kontekstu knjižnične djelatnosti = Theoretical Reflections on Information Policy in the Context of Librarianship." Bosniaca 22, no. 22 (December 2017): 9–17. http://dx.doi.org/10.37083/bosn.2017.22.9.
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U demokratskom društvu promocija, poštivanje i povezivanje čovjekovih prava i osnovnih sloboda temeljne su zadaće svake države. Uključivanje knjižnica u takve procese podupiru Europska unija i UNESCO različitim dokumentima koji se odnose na slobodan pristup informacijama, ulogu knjižnica u nacionalnoj informacijskoj politici, ulogu knjižnica u industriji znanja, zaštitu pisanog nasljeđa, razvoj informacijskih resursa i servisa, promicanje djelotvornog korištenja informacija i sl. Knjižnice, arhivi i muzeji formiraju informacijsku politiku tako što utječu na pristup građana informacijama. Takva se politika regulira vladinim legislativama (zakoni, pravila, propisi, smjernice), koji opet utječu na informacijski ciklus koji predstavlja kreaciju, organizaciju, diseminaciju ili evaluaciju informacija. Nacionalna je informacijska politika niz vladinih odluka koje su određene da potiču bolju informacijsku infrastrukturu. Ona je vladin instrument koji bi u svakoj državi omogućavao najbolju moguću mrežu informacijskih službi. Te bi službe morale određenim sredstvima ispunjavati potrebe korisnika cjelovito, brzo i u primjerenom obliku. Nacionalna informacijska politika pokriva pitanja razvoja informacijskih resursa i servisa, pružanja pristupa informacijama, promicanja djelotvornog korištenja informacija, razvoj i koordinaciju nacionalnih informacijskih aktivnosti, kao i sudjelovanje u međunarodnim informacijskim aktivnostima. = In a democratic society, promoting, respecting and linking human rights and fundamental freedoms are the fundamental tasks of each country. Involving libraries in such processes is supported by the European Union and UNESCO with various documents related to free access to information, the role of libraries in the national information policy, the role of libraries in the knowledge industry, the protection of written heritage, the development of information resources and services, the promotion of effective use of information and Fig.Libraries, archives and museums form information policy by affecting citizen access to information. Such a policy is governed by governmental legislation (laws, rules, regulations, guidelines) that again affect the information cycle that is the creation, organization, dissemination or evaluation of information. The National Information Policy is a series of decisions made by governments that are designed to encourage better information infrastructure. It is a government instrument that will provide the best possible information network in each country. These services would have to meet the needs of the users with a certain amount of resources in complete, rapid and appropriate form. The National Information Policy covers issues related to the development of information resources and services, providing access to information, promoting effective use of information, developing and coordinating national information activities, as well as participating in international information activities.
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Goncharova, N. A., A. S. Dushkin, I. N. Konopleva, and M. V. Pryakhina. "Features of Emotional and Volitional Stability of Police Officers at Various Stages of Occupational Genesis." Psychology and Law 13, no. 1 (March 30, 2023): 51–63. http://dx.doi.org/10.17759/psylaw.2023130104.
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<p style="text-align: justify;">The article deals with the issues of emotional and volitional stability, acting as the leading ones in the system of moral and psychological support for the activities of the internal affairs bodies of the Russian Federation. The purpose of the article was to analyze the features of emotional and volitional stability of police officers of the territorial bodies of the Ministry of Internal Affairs of Russia and cadets of the educational organization of the Ministry of Internal Affairs of Russia. The sample is represented by two groups of 119 people, including police officers, 65 people, cadets of the educational organization of the Ministry of Internal Affairs of Russia — 54 people. The research methods were presented by the diagnostic unit: the questionnaire for assessing neuropsychic stability “Prognosis-2” (V.Yu. Rybnikov); the test “Lifestyle Analysis” (Boston stress tolerance test), the Individual typological questionnaire L.N. Sobchik, The methodology of the study of the volitional organization of the personality of A.A.Khokhlov, The test questionnaire of A.V. Zverkov and E.V. Eidman “The study of volitional self-regulation”. Research results. The presence of significantly significant differences (p≤0.05) between the groups was established, indicating a higher level of neuropsychic stability, stress resistance and emotional-volitional regulation of police officers, which is determined by age characteristics and character accentuations. The normative indicators in both groups were not exceeded, which generally reflects the quality of professional psychological selection and the stability of the personality of police officers.</p>
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Qi, Huiyue, Fei Deng, Yinghuai Wang, Hao Zhang, Yashpal S. Kanwar, and Yingbo Dai. "Myo-Inositol Supplementation Alleviates Cisplatin-Induced Acute Kidney Injury via Inhibition of Ferroptosis." Cells 12, no. 1 (December 21, 2022): 16. http://dx.doi.org/10.3390/cells12010016.
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Myo-inositol, a carbocyclic sugar, is believed to be relevant to renal pathobiology since the kidney is the major site for its catabolism. Its role in acute kidney injury (AKI) has not been fully investigated. Ferroptosis, a unique form of regulated cell death, is involved in various types of renal injuries. The relevance of myo-inositol with respect to the process of ferroptosis has not been explored either. Herein, our current exploratory studies revealed that supplementation of myo-inositol attenuates cisplatin-induced injury in cultured Boston University mouse proximal tubular (BUMPT) cells and renal tubules in vivo. Moreover, our studies unraveled that metabolic parameters pertaining to ferroptosis were disrupted in cisplatin-treated proximal tubular cells, which were seemingly remedied by the administration of myo-inositol. Mechanistically, we noted that cisplatin treatment led to the up-regulation of NOX4, a key enzyme relevant to ferroptosis, which was normalized by the administration of myo-inositol. Furthermore, we observed that changes in the NOX4 expression induced by cisplatin or myo-inositol were modulated by carboxy-terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase. Taken together, our investigation suggests that myo-inositol promotes CHIP-mediated ubiquitination of NOX4 to decelerate the process of ferroptosis, leading to the amelioration of cisplatin-induced AKI.
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Singh, Kamini, Trang Uyen Nguyen, Eric Nels Pederson, Vinay Kumar, Xiaoling Yun, and Zhengqing Ouyang. "Abstract C082: Decoding the KRAS-dependent proteome through the ribosomal lens." Cancer Research 84, no. 2_Supplement (January 16, 2024): C082. http://dx.doi.org/10.1158/1538-7445.panca2023-c082.
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Abstract Our study addresses the gap in understanding the KRAS-specific translation landscape and functional proteome in cancer. We demonstrate that mutant KRAS drives distinct mechanisms of translational control to fuel cancer growth. By leveraging ribosome footprinting and advanced sequencing techniques, we investigate the impact of sotorasib, a targeted inhibitor of G12C mutant KRAS activity, on translation. Notably, KRAS (G12C) inhibition profoundly alters the translation of ribosomal proteins and translation elongation factors. Additionally, we reveal that KRAS inhibition resulted in ribosome stalling on a specific subset of mRNAs. Acute treatment with sotorasib hampers the translation of crucial oncogenic proteins, including MYC, as well as proteins involved in metabolism. These translational changes are facilitated by specific RNA motifs and RNA binding proteins that respond to KRAS activity. In essence, our study delineates the KRAS (G12C)-specific regulation of translation and elucidates the mechanism underlying KRAS (G12C)-mediated control over the cancer proteome. Citation Format: Kamini Singh, Trang Uyen Nguyen, Eric Nels Pederson, Vinay Kumar, Xiaoling Yun, Zhengqing Ouyang. Decoding the KRAS-dependent proteome through the ribosomal lens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C082.
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Wang, Yue, Tom Chou, and Blerta Shtylla. "Abstract B034: Order-of-mutation effects on cancer progression: Models for myeloproliferative neoplasm." Cancer Research 84, no. 3_Supplement_2 (February 1, 2024): B034. http://dx.doi.org/10.1158/1538-7445.canevol23-b034.
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Abstract In some patients with myeloproliferative neoplasms (MPN), two genetic mutations are often found, JAK2 V617F and one in the TET2 gene. Whether or not one mutation is present will influence how the other subsequent mutation affects the regulation of gene expression. When both mutations are present, the order of their occurrence has been shown to influence disease progression and prognosis. We propose a nonlinear ordinary differential equation (ODE) model and a Moran process models to explain the non-additive and non-commutative mutation effects on recent clinical observations of gene expression patterns, proportions of cells with different mutations, and ages at diagnosis of MPN. These observations consistently shape our modeling framework. Our key proposal is that bistability in gene expression provides a natural explanation for many observed order-of-mutation effects. We also propose potential experimental measurements that can be used to confirm or refute predictions of our models. Citation Format: Yue Wang, Tom Chou, Blerta Shtylla. Order-of-mutation effects on cancer progression: Models for myeloproliferative neoplasm [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B034.
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Martinez-Marin, Dalia, Jenna C. van Wunnik, Monica Sharma, and Kevin Pruitt. "Abstract B03: Role of DVL in transcription and epigenetic regulation of immunoregulatory genes in triple-negative breast cancer." Cancer Immunology Research 10, no. 12_Supplement (December 1, 2022): B03. http://dx.doi.org/10.1158/2326-6074.tumimm22-b03.
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Abstract Introduction: Dishevelled (DVL) is a crucial component of Wnt-signaling and is vital for other physiological processes. There are three DVL paralogs, yet the paralog-specific functions and their regulation remain poorly understood. One of the goals of our study is to define how DVL1 mediates Wnt-signaling specificity and how it regulates the transcription of genes that impact tumor-intrinsic modulation of immune cell recruitment. While several studies suggest that DVL proteins could serve as critical mediators of malignancy for breast cancer and other cancer types, the mechanism by which DVL contributes to breast tumor progression and tumor immunology remain unanswered. This study utilizes data from our recent DVL ChIP-seq and RNA-seq analyses, publicly available data, genomic analyses, and other bioinformatics tools to investigate novel mechanisms of how DVL coordinates downstream signaling. Our study seeks to define the elusive function of nuclear DVL with respect to epigenetic and transcriptional regulation in models of triple-negative breast cancer. Methods: DVL ChIP-sequenced reads were aligned against GRCh38.p14, and peaks visualized using an integrative genomic viewer. RNA-seq FASTQ files were trimmed and aligned to GRCh38.p14; read counts were analyzed with edgeR and resulting differentially expressed genes with R and Cytoscape. To determine possible DVL binding partners, transcription factor and protein-protein interaction database mining and subsequent co-immunoprecipitation were performed. Results: Although much remains unknown regarding DVL function and regulation, the discovery of its translocation to the nucleus, binding to novel genomic loci, and regulation of novel gene expression raised new functionality. Our analysis shows DVL binding to core-promoter elements in essential immunological regulatory genes such as STAT1, IFN-y, HLA (-A, B, C, Ds, E, F), and interleukins. Data mining and co-immunoprecipitation analysis have identified several possible nuclear DVL binding partners, including candidate transcription factors that partner with DVL genes to regulate immune cell responses in the tumor microenvironment. DVL KO and WT transcriptional regulation analysis also identified several differentially expressed immunological genes. Summary: We have not only identified DVL binding to the promoter of genes involved in tumorigenesis and immune function but also identified possible DVL binding partners that aid in the regulation of these genes. These findings and future in silico and in vivo approaches will further define a novel DVL regulatory role of tumor and immune signaling in triple-negative breast cancer. Citation Format: Dalia Martinez-Marin, Jenna C van Wunnik, Monica Sharma, Kevin Pruitt. Role of DVL in transcription and epigenetic regulation of immunoregulatory genes in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B03.
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Giurlani, Walter, Martina Vizza, Stefano Mauro Martinuzzi, Andrea Comparini, Marco Bonechi, Margherita Verrucchi, Andrea Caneschi, and Massimo Innocenti. "New Frontiers in Electrodeposition for More Sustainable Electroplating Processes." ECS Meeting Abstracts MA2022-02, no. 23 (October 9, 2022): 956. http://dx.doi.org/10.1149/ma2022-0223956mtgabs.
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Although technological and processing advancements occurred in the past forty years, industrial firms are still struggling to provide solutions to corrosion protection as well as reduction of toxic wastes. Specifically, large-scale industrialization of electroplating techniques will continue to be limited by strict environmental regulations. Moreover, price volatility of the highly demanding electroplated materials like gold, palladium, copper and nickel will heavily impact the market in the next years. In that respect, alloy plating offers better answers in terms of economic growth and environmental sustainability due to fine tuning composition, morphology and crystallinity [1]. The main categories of alloy compounds are presented and the most important properties for the manufacturing process discussed. Particular attention is devoted to advances in industrial quality control and viable solutions for the reduction of precious metal content in electroplated accessories as well as replacement of cyanide and nickel baths with non-toxic compounds, also considering the commercial needs of wear resistance and aesthetic characteristics of gloss. The electrodeposition of Cu-Sn alloys (bronze) has earned considerable interest thanks to the chemical-physical properties of this alloy, which make it a valid substitute for nickel in fashion industry. Generally, most of the bronze coatings are electroplated starting from baths containing cyanides, and the metal precursors are selected as cyanide compounds. Free cyanide is a well-known problem in the galvanic production cycle both in terms of toxicity for the workers as well as for the environment, and in terms of costs associated with its disposal. The aim of this study is to develop an electroplating bath totally cyanide-free, therefore formulated in an innovative way and which, in addition to being free from this dangerous species, has an eco-friendly support electrolyte. To achieve this goal, methanesulfonic acid (MSA) was chosen as electrolyte, which is biodegradable as part of the natural sulfur cycle. We've studied different formulations in terms of metal precursors, organic additives and their concentrations [2-3]. The same cyanide issue is present also in for the electrodeposition of silver, for this reason the influence of polyethyleneimine (PEI) as additive for cyanide-free silver bath, in combination with 5,5-dimethylhydantoin (DMH) as complexing agent, was studied [4]. Chronoamperometry was used to investigate the electrodeposition mechanism, which is found to be a three-dimensional diffusion-controlled nucleation and growth mechanism, according to the Scharifker–Mostany’s model. Smoother, brighter and blue colored silver deposits are obtained in the presence of PEI in a Hull’s cell test, at low density current. Eventually, the influence of nitrate anion is also investigated. The presence of nitrate increases the range of current density allowing for an effective Ag deposition. We also investigated the use of modulated currents to increase the throwing power of electroplating, obtaining a more uniform deposition and reducing the amount of metals but maintaining the required characteristics. Pulsed current justifies its practical application mainly through its ability to influence the mechanisms of electrocrystallisation, which in turn control the mechanical and physical properties of the deposited metal. By simply adjusting the amplitude and length of the pulses, it is possible to control not only the composition and thickness, in atomic order, of the deposits, but to improve their characteristics such as grain size, porosity and homogeneity [5]. The authors acknowledge Regione Toscana POR CreO FESR 2014-2020 – azione 1.1.5 sub-azione a1 – Bando 1 “Progetti Strategici di ricerca e sviluppo” which made possible the projects “A.C.A.L. 4.0” (CUP 3553.04032020.158000165_1385), “A.M.P.E.R.E.” (CUP 3553.04032020.158000223_1538) and “GoodGalv” (3647.04032020.157000060). References [1] Giurlani, W.; Zangari, G.; Gambinossi, F.; Passaponti, M.; Salvietti, E.; Di Benedetto, F.; Caporali, S.; Innocenti, M. Electroplating for Decorative Applications: Recent Trends in Research and Development. Coatings 2018, 8, 260, doi:10.3390/coatings8080260. [2] Fabbri, L.; Sun, Y.; Piciollo, E.; Salvietti, E.; Zangari, G.; Passaponti, M.; Innocenti, M. Electrodeposition of White Bronzes on the Way to CZTS Absorber Films. J. Electrochem. Soc. 2020 , 167, 022513, doi: 10.1149/1945-7111/ab6c59. [3] Fabbri, L.; Giurlani, W.; Mencherini, G.; De Luca, A.; Passaponti, M.; Piciollo, E.; Fontanesi, C.; Caneschi, A.; Innocenti, M. Optimisation of Thiourea Concentration in a Decorative Copper Plating Acid Bath Based on Methanesulfonic Electrolyte. Coatings 2022, 12, 376, doi:10.3390/coatings12030376. [4] Pizzetti, F.; Salvietti, E.; Giurlani, W.; Emanuele, R.; Fontanesi, C.; Innocenti, M. Cyanide-free silver electrodeposition with polyethyleneimine and 5,5-dimethylhydantoin as organic additives for an environmentally friendly formulation. J. Electroanal. Chem. 2022, 911, 116196, doi:10.1016/j.jelechem.2022.116196. [5] Popov, K.I.; Nikolić, N.D. General Theory of Disperse Metal Electrodeposits Formation. In; Djokić, S.S., Ed.; Modern Aspects of Electrochemistry; Springer US: Boston, MA, 2012; Vol. 54, pp. 1–62 ISBN 978-1-4614-2379-9.
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Soares, Zamira G., Emily Berry, Dakarai Esgdaille, Jennifer Twardowski, and Stephano S. Mello. "Abstract B094: The role of paraspeckles and splicing regulation in driving basal-like pancreatic cancer." Cancer Research 84, no. 2_Supplement (January 16, 2024): B094. http://dx.doi.org/10.1158/1538-7445.panca2023-b094.
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Abstract The basal-like pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of mesenchymal PDAC that resists treatment and has a poor prognosis. Understanding the mechanisms driving basal-like PDAC biology will be essential for development of treatment strategies for this aggressive tumor. We have previously shown that loss of the tumor-suppressive non-coding RNA Neat1 recapitulate the phenotype of Arid1a-deficient mice (a component of the SWI/SNF chromatin remodeling complex) in a mouse model for PDAC, with loss of exocrine pancreatic identity and development of acinar- and ductal-derived lesions (Mello et al., 2017), suggesting that Neat1 and Arid1a may share a common molecular mechanism. We now demonstrate that the loss of these two divergent genes induce the emergence of basal-like PDAC. This provides an opportunity to probe for shared features specific to Neat1- and Arid1a-deficient PDAC, as compared to PDAC in which both genes are functional. Notably, our data indicate that both Neat1- and Arid1a-deficient pancreatic cells fail to form nuclear paraspeckles, i.e. structures implicated in the retention of RNA splicing factors. Consistent with this idea, we also find significantly increased exon-skipping, including a sub-set of such events shared between Neat1- and Arid1a-deficient PDAC. In addition, nucleotide sequence motifs associated with exon-skipping locations suggest involvement of RNA splicing factors known to accumulate in paraspeckles, such as Srsf1, Srsf2, Srsf10, Rbm38, Dazap1 and others. We also show that, upon genetic or pharmacological attenuation of splicing regulator function, basal-like PDAC develop epithelial features, reminiscent of mesenchymal-epithelial transition, reduce both their proliferation and migration potential and undergo cell death. Our findings provide an important opportunity to elucidate the molecular pathways that link aberrant RNA splicing and paraspeckle deficiency to basal-like PDAC, providing new insight for the development of mechanism-based novel PDAC treatment strategies to improve patient outcome. Citation Format: Zamira G. Soares, Emily Berry, Dakarai Esgdaille, Jennifer Twardowski, Stephano S. Mello. The role of paraspeckles and splicing regulation in driving basal-like pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B094.
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Canel, Marta, Aleksandra Slawinska, David W. Lonergan, Ashwin A. Kallor, Rosie Upstill-Goddard, Catherine Davidson, Alex von Kriegsheim, et al. "Abstract C019: FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer." Cancer Research 82, no. 22_Supplement (November 15, 2022): C019. http://dx.doi.org/10.1158/1538-7445.panca22-c019.
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Abstract Immunotherapy for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC) has shown limited efficacy. Poor CD8 T-cell infiltration, low neoantigen load and a highly immunosuppressive tumor microenvironment are key factors that contribute to this lack of response. Here, we identify a novel role for Focal Adhesion Kinase (FAK) in regulating type-II interferon signalling in human and murine PDAC cells and tumors, leading to suppression of antigen processing and presentation pathways critical for T-cell tumor recognition. We find that FAK loss promotes expression of the immunoproteasome and MHC-I, resulting in a significant increase in the diversity of antigens presented by FAK-/- PDAC cells. We show that regulation of the immunoproteasome subunit Psmb8 (β5i) is a critical determinant of this response, optimising the physicochemical properties of the peptide repertoire for high-affinity binding to MHC-I. Expression of the immunoproteasome and MHC-I can be further amplified in a STAT1-dependent manner via co-depletion of FAK and STAT3, leading to extensive CD8 T-cell infiltration into PDAC tumors and further restraint of tumor growth. Regulation of antigen processing and presentation by FAK preferentially occurs in human and murine PDAC cells and tumors of the classical/progenitor molecular subtype, further suggesting that precision medicine approaches based on molecular subtyping should be integrated into current and future clinical testing of FAK targeted therapies for the treatment of pancreatic cancer. Citation Format: Marta Canel, Aleksandra Slawinska, David W. Lonergan, Ashwin A. Kallor, Rosie Upstill-Goddard, Catherine Davidson, Alex von Kriegsheim, Andrew V. Biankin, Adam Bryron, Javier Alfaro, Alan Serrels. FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C019.