Exploring pharmacodynamics of immunosuppresive agents in transplantation

Supported by advancements in technology, surgical techniques and immunosuppressive drugs, solid organ transplantation has become the preferred solution to end stage organ failure. The first solid organ transplantation was performed in 1954 under supervision of Joseph Murray in the Peter Bent Brigham Hospital in Boston. A kidney from a healthy donor was transplanted into his identical twin, who suffered from chronic glomerulonephritis. The transplanted organ functioned immediately and the recipient survived for 25 years while the donor lived for another 56 years. Since the twins were genetically identical, no suppression of the immune system was needed. Transplantation between individuals other than identical twins was made possible a decade later by the use of the combination of azathioprine and corticosteroids, achieving a 1 year allograft1 survival rate of 40 to 50 percent

A Tool and Methodology for Rapid Assessment and Monitoring of Heritage Places in a Disaster and Post- Disaster Context – Syria as a Case Study

Over the past decade, cultural heritage in the Middle East and North Africa has been at risk of irreparable damage through conflict, looting, and cessation of official monitoring and development controls. Various organizations are seeking to monitor and record the extent of damage through satellite imagery and media reports. While the remote assessment of cultural heritage sites and buildings has the advantage of allowing for monitoring of cultural heritage properties from afar, its main limitation is the reduced level of certainty and accuracy in the assessment. It is therefore also essential to have tools and methods in place for on-the-ground condition assessment and systematic recording of data, for use as and when opportunities arise. In the Syrian context, given the threats and damage to archaeological sites, museum collections, libraries and archives, it is essential to develop strategies for emergency recording, assessment and response, and to build up local expertise and provide technical assistance in order to safeguard Syria’s rich cultural heritage. This paper presents the approaches used in the development of a pilot Historic Environment Record (HER) for Syria which began life as an initiative of the advocacy organization Shirīn, and which has since undergone considerable development. It describes the methodologies and standards developed for use in a geodatabase to provide a systematic way to undertake and record rapid and on the ground condition and risk assessments of cultural heritage. The system is being customized to meet post-war/disaster challenges including emergency recording, measuring of damage and threat, and prioritization of resources and intervention activities. The database aims to set procedures for carrying out systematic rapid condition assessment (to record damage) and risk assessment (to record threat and level of risk) of heritage places, on the basis of both on the ground assessment and remote sensing. Given the large number of heritage properties damaged by conflict in the MENA region, the implementation of rapid assessment methods to identify quickly and record level of damage and condition is essential, as these will provide the evidence to support effective prioritization of efforts and resources, and decisions on the appropriate levels of intervention and methods of treatment. Although the initial work of the research project came out of the ongoing conflict in Syria, this database and methodology has since been developed and implemented as part of the multi-institutional project Endangered Archaeology in the Middle East and North Africa (EAMENA). Given the general lack of appropriate emergency response and assessment databases, this system could also be applied in other regions facing similar threats and damage from conflict or natural disasters

Monte Carlo methods for parallel processing of diffusion equations

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2013."June 2013." Cataloged from PDF version of thesis.Includes bibliographical references (page 14).A Monte Carlo algorithm for solving simple linear systems using a random walk is demonstrated and analyzed. The described algorithm solves for each element in the solution vector independently. Furthermore, it is demonstrated that this algorithm is easily parallelized. To reduce error, each processor can compute data for an independent element of the solution, or part of the data for a given element for the solution, allowing for larger samples to decrease stochastic error. In addition to parallelization, it is also shown that a probabilistic chain termination can decrease the runtime of the algorithm while maintaining accuracy. Thirdly, a tighter lower bound for the required number of chains given a desired error is determined.by Cyrus Vafadari.S.B

Investigating the Preventive Factors of People in the Society from Attending Urban Parks during the COVID-19 Pandemic

Introduction  As urbanization and population density increase, numerous issues arise in society, including a heightened risk of contagious diseases among the population, putting society at risk and in crisis. The purpose of this study was to identify preventive factors for individuals in the community to avoid attending urban parks during the COVID-19 pandemic, as well as to evaluate the capacity of these places to promote public health and their functionality during the pandemic. Materials and Methods  Using library resources and semi-structured in-depth interviews, the research data questionnaire was obtained and for sampling and determination of sample size, simple random sampling method and Cochran formula related to unknown statistical population with error level of 0.05 were used, respectively. Then, in order to analyze the data, the first question which was prioritized was 4-1 points from the first to the fourth priority and the mean score was calculated and the same process was implemented for the second part questions, respectively. After collecting the questionnaires, the data were extracted and the frequency of each of the options in the questions was determined, then to investigate the first part question which was related to the barriers to the presence of people in urban parks during the pandemic period and should be prioritized, i.e. assigning numbers 1 to 4 based on the participants' opinions, the priority was 4 points for priority 1 score 4, priority 2 points. 3, priority 3 points 2 and priority 4 points 1 selected, After averaging the relevant score, comparing them with each other, the most important barriers were mentioned in the results section, respectively. Also, in order to investigate the questions of the second part, the first question was related to the capacity of urban parks to promote public health in pandemic conditions and should have been answered as a single choice for the very significant option of score 4, the significant option of score 3, the average score option 2 and the low-score option 1, and after the average of the relevant points and comparing it with the average capacity of the park was selected. Some of the general health promotion during pandemic were identified and mentioned in the results section. Results and Discussion The study revealed that the most significant barrier to people's presence in urban parks was the absence of health warning signs, with an average score of 3.1. Additionally, the capacity of urban parks to enhance public health received a very significant average score of 3.3. However, the performance of these parks during the COVID-19 pandemic was rated as poor, with an average score of 1.4. Other barriers identified to people's presence in parks include: - Non-conformity of urban parks design with pandemic conditions - Inappropriate layout of furniture in urban parks - Inappropriate shape, material and type of furniture in urban parks in terms of public health Also, the overall results of urban parks capacity in increasing public health and performance of these places during covid-19 pandemic are as follows: In relation to the capacity of urban parks in order to increase public health in comparison with other urban uses, the results of the survey of the received data are that out of 230 people in the study, 99 people evaluated the capacity of these places as very significant (43%), 103 significant (45%), 21 moderate (9%) and 7 (3%). In relation to how the current urban parks play a role in covid-19 pandemic compared to other urban uses, the results of the data survey are as such that out of 230 people present in the research, 5 people performed this Places were assessed as excellent (2%), 11 were good (5%), 53 were moderate (23%) and 156 were weak (70%). Conclusion Overall, it can be concluded that urban parks have the potential to significantly promote public health, but during the pandemic period, their effectiveness was limited due to various barriers. It is recommended that designers, urban planners, and health professionals work together to create multi-functional designs that address existing barriers as much as possible. This would enable people to attend urban parks during the pandemic with less concern and potentially reduce the negative consequences of pandemic outbreaks and quarantine

A normal genetic variation modulates synaptic MMP-9 protein levels and the severity of schizophrenia symptoms

Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients

Phospho-specific flow cytometry for pharmacodynamic monitoring of immunosuppressive therapy in transplantation

Organ transplant recipients frequently suffer from toxicity or from lack of efficacy of immunosuppressive drugs, which can be attributed to individual variations in drug sensitivity. This problem can be resolved by applying pharmacodynamic monitoring that focuses on measuring the biological effects of drugs. Here we discuss the new technique called phospho-specific flow cytometry to monitor the activity of intracellular immune signaling pathways at the single-cell level in whole blood samples. Through this tool the efficacy of immunosuppressive medication can be assessed, novel targets can be identified, and differences in drug sensitivity between cells and patients can be clarified

If Racism Vanished for a Day

This picture book was co-written and illustrated by 17 children from Bristol Schools. They think it's important to learn from children's experiences of racism so have posed simple sentences and illustrative responses for readers to critically reflect on

The malleable brain: plasticity of neural circuits and behavior: A review from students to students

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation (LTP) and long-term depression (LTD) respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by LTP and LTD, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity.Fil: Schaefer, Natascha. University of Wuerzburg; AlemaniaFil: Rotermund, Carola. University of Tuebingen; AlemaniaFil: Blumrich, Eva Maria. Universitat Bremen; AlemaniaFil: Lourenco, Mychael V.. Universidade Federal do Rio de Janeiro; BrasilFil: Joshi, Pooja. Robert Debre Hospital; FranciaFil: Hegemann, Regina U.. University of Otago; Nueva ZelandaFil: Jamwal, Sumit. ISF College of Pharmacy; IndiaFil: Ali, Nilufar. Augusta University; Estados UnidosFil: García Romero, Ezra Michelet. Universidad Veracruzana; MéxicoFil: Sharma, Sorabh. Birla Institute of Technology and Science; IndiaFil: Ghosh, Shampa. Indian Council of Medical Research; IndiaFil: Sinha, Jitendra K.. Indian Council of Medical Research; IndiaFil: Loke, Hannah. Hudson Institute of Medical Research; AustraliaFil: Jain, Vishal. Defence Institute of Physiology and Allied Sciences; IndiaFil: Lepeta, Katarzyna. Polish Academy of Sciences; ArgentinaFil: Salamian, Ahmad. Polish Academy of Sciences; ArgentinaFil: Sharma, Mahima. Polish Academy of Sciences; ArgentinaFil: Golpich, Mojtaba. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Nawrotek, Katarzyna. University Of Lodz; ArgentinaFil: Paid, Ramesh K.. Indian Institute of Chemical Biology; IndiaFil: Shahidzadeh, Sheila M.. Syracuse University; Estados UnidosFil: Piermartiri, Tetsade. Universidade Federal de Santa Catarina; BrasilFil: Amini, Elham. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Pastor, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Wilson, Yvette. University of Melbourne; AustraliaFil: Adeniyi, Philip A.. Afe Babalola University; NigeriaFil: Datusalia, Ashok K.. National Brain Research Centre; IndiaFil: Vafadari, Benham. Polish Academy of Sciences; ArgentinaFil: Saini, Vedangana. University of Nebraska; Estados UnidosFil: Suárez Pozos, Edna. Instituto Politécnico Nacional; MéxicoFil: Kushwah, Neetu. Defence Institute of Physiology and Allied Sciences; IndiaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Turner, Anthony J.. University of Leeds; Reino Unid